BioMed Research International: Molecular Imaging The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Molecular Image-Guided Theranostic and Personalized Medicine 2014 Wed, 25 Mar 2015 12:48:03 +0000 Hong Zhang, Mei Tian, Ignasi Carrio, Ali Cahid Civelek, and Yasuhisa Fujibayashi Copyright © 2015 Hong Zhang et al. All rights reserved. Adenocarcinoma with BAC Features Presented as the Nonsolid Nodule Is Prone to Be False-Negative on 18F-FDG PET/CT Tue, 24 Mar 2015 14:28:14 +0000 Purpose. The present study investigated which type of adenocarcinoma with BAC features was prone to be false-negative on 18F-FDG PET/CT. Materials and Methods. A retrospective study was performed on 51 consecutive patients with localized adenocarcinoma with BAC features. CT and PET were assessed for lesion size, GGO percentage, and SUVmax. Lesions with FDG uptake the same as or more than mediastinal blood-pool activity were considered as PET-positive. Results. Of the 51 cases, 19.6% presented as pure GGO nodules, 31.4% as mixed nodules, and 49.0% as solid nodules. None of the pure GGO nodules was 18F-FDG avid, compared with 37.5% of mixed nodules and 96.0% of solid nodules (, ). In the mixed nodule group, SUVmax was negatively correlated with GGO percentage (; ). The positive detection rate of 18F-FDG PET/CT was 50.0%, 55.6%, and 100% in tumors 1.1–2.0 cm, 2.1–3.0 cm, and >3.0 cm in diameter, respectively (, ). General linear model factor analysis showed that the GGO was an important factor contributing to false-negative PET/CT results (, ), but lesion size was not (, ). Conclusions. The present study indicated that the adenocarcinoma with BAC features presented as nonsolid nodule is prone to be false negative on 18F-FDG PET/CT. Hu-bing Wu, Lijuan Wang, Quan-shi Wang, Yan-jian Han, Hong-sheng Li, Wen-lan Zhou, and Ying Tian Copyright © 2015 Hu-bing Wu et al. All rights reserved. Prognostic Value of -Pertechnetate Thyroid Scintigraphy in Radioiodine Therapy in a Cohort of Chinese Graves’ Disease Patients: A Pilot Clinical Study Tue, 24 Mar 2015 14:02:59 +0000 Objectives. This study is to assess the prognostic value of -pertechnetate thyroid scintigraphy for predicting the outcomes of fixed low dose of radioiodine therapy (RIT) in a cohort of Chinese Graves’ disease (GD) patients. Materials and Methods. This is a retrospective study of GD patients who received RIT with a single dose of radioiodine (5 mCi). All the patients received -pertechnetate thyroid scintigraphy prior to RIT. Thyroid mass, -pertechnetate uptake, gender, age at diagnosis, duration of the disease, ophthalmopathy, and serum levels of FT4, FT3, TT4, and TT3 prior to RIT were analyzed as potential interference factors for outcomes of RIT. Results. One hundred and eighteen GD patients who completed RIT were followed up for 12 months. The outcomes (euthyroidism, hypothyroidism, and hyperthyroidism) were found to be significantly associated with thyroid mass and -pertechnetate uptake. Patients with thyroid mass ≤ 40.1 g or -pertechnetate uptake ≤ 15.2% had higher treatment success. Conclusions. A fixed low dose of 5 mCi radioiodine seems to be practical and effective for the treatment of Chinese GD patients with thyroid mass ≤ 40.1 g and -pertechnetate uptake ≤ 15.2%. This study demonstrates -pertechnetate thyroid scintigraphy is an important prognostic factor for predicting the outcomes of RIT. Haifeng Hou, Shu Hu, Rong Fan, Wen Sun, Xiaofei Zhang, and Mei Tian Copyright © 2015 Haifeng Hou et al. All rights reserved. The Diagnostic Value of 18F-FDG PET/CT in Association with Serum Tumor Marker Assays in Breast Cancer Recurrence and Metastasis Tue, 24 Mar 2015 12:08:47 +0000 Background. After initial treatment of breast cancer (BC), monitoring locoregional recurrence and distant metastases is a great clinical challenge. Objective. To evaluate the efficacy of PET/CT in association with serum tumor makers in BC follow-up. Methods. Twenty-six women with a history of modified radical mastectomy were evaluated by 18F-FDG PET/CT. The results of PET/CT were compared with those of conventional imaging techniques (CITs) (including mammography, chest radiography, CT, MRI, ultrasound, and bone scintigraphy). Serum tumor markers of CEA, CA 125, and CA 15-3 in the BC patients were also analyzed in association with the results of PET/CT. Results. Compared with CITs, PET/CT was more sensitive to detect the malignant foci and had better patient-based sensitivity and specificity. The mean CA 15-3 serum level was significantly higher in the confirmed positive patients of PET/CT results than in the confirmed negative ones, while there were no significant differences in the serum levels of CEA and CA 125 of both groups. Conclusion. PET/CT is a highly efficient tool for BC follow-up compared with CITs. The high serum levels of CA 15-3 in confirmed positive PET/CT patients indicated the clinical value of CA 15-3 in BC follow-up. Ying Dong, Haifeng Hou, Chunyan Wang, Jing Li, Qiong Yao, Said Amer, and Mei Tian Copyright © 2015 Ying Dong et al. All rights reserved. Imaging Infection and Inflammation Tue, 24 Mar 2015 11:55:27 +0000 Alberto Signore, Andor W. J. M. Glaudemans, Filippo Galli, and François Rouzet Copyright © 2015 Alberto Signore et al. All rights reserved. Molecular and Functional Imaging of Internet Addiction Tue, 24 Mar 2015 11:25:18 +0000 Maladaptive use of the Internet results in Internet addiction (IA), which is associated with various negative consequences. Molecular and functional imaging techniques have been increasingly used for analysis of neurobiological changes and neurochemical correlates of IA. This review summarizes molecular and functional imaging findings on neurobiological mechanisms of IA, focusing on magnetic resonance imaging (MRI) and nuclear imaging modalities including positron emission tomography (PET) and single photon emission computed tomography (SPECT). MRI studies demonstrate that structural changes in frontal cortex are associated with functional abnormalities in Internet addicted subjects. Nuclear imaging findings indicate that IA is associated with dysfunction of the brain dopaminergic systems. Abnormal dopamine regulation of the prefrontal cortex (PFC) could underlie the enhanced motivational value and uncontrolled behavior over Internet overuse in addicted subjects. Further investigations are needed to determine specific changes in the Internet addictive brain, as well as their implications for behavior and cognition. Yunqi Zhu, Hong Zhang, and Mei Tian Copyright © 2015 Yunqi Zhu et al. All rights reserved. Somatostatin Receptor Based Imaging and Radionuclide Therapy Tue, 24 Mar 2015 09:21:48 +0000 Somatostatin (SST) receptors (SSTRs) belong to the typical 7-transmembrane domain family of G-protein-coupled receptors. Five distinct subtypes (termed SSTR1-5) have been identified, with SSTR2 showing the highest affinity for natural SST and synthetic SST analogs. Most neuroendocrine tumors (NETs) have high expression levels of SSTRs, which opens the possibility for tumor imaging and therapy with radiolabeled SST analogs. A number of tracers have been developed for the diagnosis, staging, and treatment of NETs with impressive results, which facilitates the applications of human SSTR subtype 2 (hSSTr2) reporter gene based imaging and therapy in SSTR negative or weakly positive tumors to provide a novel approach for the management of tumors. The hSSTr2 gene can act as not only a reporter gene for in vivo imaging, but also a therapeutic gene for local radionuclide therapy. Even a second therapeutic gene can be transfected into the same tumor cells together with hSSTr2 reporter gene to obtain a synergistic therapeutic effect. However, additional preclinical and especially translational and clinical researches are needed to confirm the value of hSSTr2 reporter gene based imaging and therapy in tumors. Caiyun Xu and Hong Zhang Copyright © 2015 Caiyun Xu and Hong Zhang. All rights reserved. Ghrelin Improves Functional Survival of Engrafted Adipose-Derived Mesenchymal Stem Cells in Ischemic Heart through PI3K/Akt Signaling Pathway Tue, 24 Mar 2015 08:38:27 +0000 Mesenchymal stem cells (MSCs) have been proposed as a promising cell population for cell therapy and regenerative medicine applications. However, the low retention and poor survival of engrafted cells hampered the therapeutic efficacy of engrafted MSCs. Ghrelin is a 28-amino-acid peptide hormone and is proved to exert a protective effect on the cardiovascular system. This study is designed to investigate the protective effects of ghrelin on engrafted adipose-derived mesenchymal stem cells (ADMSCs) and its beneficial effects with cellular therapy in mice myocardial infarction (MI). Results showed that intramyocardial injection of ADMSCs combining with ghrelin administration inhibited host cardiomyocyte apoptosis, reduced fibrosis, and improved cardiac function. To reveal possible mechanisms, ADMSCs were subjected to hypoxia/serum deprivation (H/SD) injury to simulate ischemic conditions in vivo. Ghrelin (10−8 M, 33712 pg/ml) improved ADMSCs survival under H/SD condition. Western blot assay revealed that ghrelin increased AKT phosphorylation both in vivo and in vitro, decreased the proapoptotic protein Bax, and increased the antiapoptotic protein Bcl-2 in vitro, while these effects were abolished by PI3K inhibitor LY294002. These revealed that ghrelin may serve as a promising candidate for hormone-driven approaches to improve the efficacy of mesenchymal stem cell-based therapy for cardiac ischemic disease via PI3K/AKT pathway. Dong Han, Wei Huang, Sai Ma, Jiangwei Chen, Lina Gao, Tong Liu, Rongqing Zhang, Xiujuan Li, Congye Li, Miaomiao Fan, Yundai Chen, and Feng Cao Copyright © 2015 Dong Han et al. All rights reserved. In Vivo Evaluation of TNF-Alpha in the Lungs of Patients Affected by Sarcoidosis Thu, 19 Mar 2015 13:46:17 +0000 Introduction. Sarcoidosis is a multisystemic granulomatous disorder characterized by multiple noncaseating granulomas involving intrathoracic lymph nodes and lung parenchyma. Recently, the use of anti-tumor necrosis factor alpha (anti-TNFα) agents has been introduced for therapy of chronic and refractory sarcoidosis with controversial results. Infliximab (Remicade) is a chimeric monoclonal antibody (mAb) that recognizes and binds TNFα, neutralizing its biological effects. In the present study, labelled infliximab was used to study the expression of TNFα in sarcoid lesions and to evaluate its role as a predictive marker in response to therapy with Remicade. Material and Methods. A total of 10 patients with newly diagnosed sarcoidosis were enrolled together with 10 control patients affected by rheumatoid arthritis. All patients were studied by planar imaging of the chest with -infliximab at 6 h and 24 h and total body [18F]-FDG PET/CT. Regions of interest were drawn over the lungs and the right arm and target-to-background ratios were analysed for -infliximab. SUVmean and SUVmax were calculated over lungs for FDG. Results and Discussion. Image analysis showed low correlation between T/B ratios and BAL results in patients despite positivity at [18F]-FDG PET. Conclusion. In conclusion, patients with newly diagnosed pulmonary sarcoidosis, with FDG-PET and BAL positivity, showed a negative -infliximab scintigraphy. Filippo Galli, Tiziana Lanzolla, Vittorio Pietrangeli, Gaurav Malviya, Alberto Ricci, Pierdonato Bruno, Paola Ragni, Francesco Scopinaro, Salvatore Mariotta, and Alberto Signore Copyright © 2015 Filippo Galli et al. All rights reserved. The Value of Cerebral CT Angiography with Low Tube Voltage in Detection of Intracranial Aneurysms Sun, 01 Feb 2015 12:22:17 +0000 Objective. The aim of this study is to investigate the value of cerebral CT angiography (CTA) with low tube voltage in detection of intracranial aneurysms. Materials and Methods. A total of 294 consecutive patients with spontaneous subarachnoid hemorrhage (SAH) were enrolled in this study and randomly assigned into conventional voltage CTA (C-CTA) group and low voltage CTA (L-CTA) group. The objective and subjective image qualities were analyzed and compared between C-CTA and L-CTA groups. With the results of 3D-DSA as “gold standard,” the sensitivity, specificity, and accuracy of C-CTA and L-CTA in diagnosis of aneurysms were calculated and compared with each other. Results. Compared with group C-CTA, the CT dose index volume (CTDIvol) of group L-CTA reduced by 35.65%. There were no significant differences between C-CTA and L-CTA groups regarding objective and subjective image qualities. The sensitivity, specificity, and accuracy of L-CTA in diagnosis of aneurysms were 95.16%, 99.72%, and 99.42%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the C-CTA and L-CTA groups. Conclusion. The value of cerebral CTA with 100 kV low tube voltage in detection of intracranial aneurysms is significant, and it should be recommended as a routine scan method. Kun Tang, Rui Li, Jie Lin, Xiangwu Zheng, Ling Wang, and Weiwei Yin Copyright © 2015 Kun Tang et al. All rights reserved. Intramyocardial Hemorrhage: An Enigma for Cardiac MRI? Sun, 01 Feb 2015 11:40:16 +0000 Cardiovascular magnetic resonance (CMR) is a useful noninvasive technique for determining the presence of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH), frequently occurring in patients after reperfused myocardial infarction (MI). MVO, or the so-called no-reflow phenomenon, is associated with adverse ventricular remodeling and a poor prognosis during follow-up. Similarly, IMH is considered a severe damage after revascularization by percutaneous primary coronary intervention (PPCI) or fibrinolysis, which represents a worse prognosis. However, the pathophysiology of IMH is not fully understood and imaging modalities might help to better understand that phenomenon. While, during the past decade, several studies examined the distribution patterns of late gadolinium enhancement with different CMR sequences, the standardized CMR protocol for assessment of IMH is not yet well established. The aim of this review is to evaluate the available literature on this issue, with particular regard to CMR sequences. New techniques, such as positron emission tomography/magnetic resonance imaging (PET/MRI), could be useful tools to explore molecular mechanisms of the myocardial infarction healing process. Camilla Calvieri, Gabriele Masselli, Riccardo Monti, Matteo Spreca, Gian Franco Gualdi, and Francesco Fedele Copyright © 2015 Camilla Calvieri et al. All rights reserved. Predictive Value of Interim PET/CT in DLBCL Treated with R-CHOP: Meta-Analysis Sun, 01 Feb 2015 10:00:24 +0000 Objective. We conducted a meta-analysis to evaluate the predictive value of interim 18F-FDG PET/CT in patients with DLBCL treated with R-CHOP chemotherapy. Methods. We searched for articles published in PubMed, ScienceDirect, Wiley, Scopus, and Ovid database from inception to March 2014. Articles related to interim PET/CT in patients with DLBCL treated with R-CHOP chemotherapy were selected. PFS with or without OS was chosen as the endpoint to evaluate the prognostic significance of interim PET/CT. Results. Six studies with a total of 605 cases were included. The sensitivity of interim PET/CT ranged from 21.2% to 89.7%, and the pooled sensitivity was 52.4%. The specificity of interim PET/CT ranged from 37.4% to 90.7%, and the pooled specificity was 67.8%. The pooled positive likelihood ratio and negative likelihood ratio were 1.780 and 0.706, respectively. The explained AUC was 0.6978 and the was 0.6519. Conclusions. The sensitivity and specificity of interim PET/CT in predicting the outcome of DLBCL patients treated with R-CHOP chemotherapy were not satisfactory (52.4% and 67.8%, resp.). To improve this, some more work should be done to unify the response criteria and some more research to assess the prognostic value of interim PET/CT with semiquantitative analysis. Na Sun, Jinhua Zhao, Wenli Qiao, and Taisong Wang Copyright © 2015 Na Sun et al. All rights reserved. Large-Vessel Vasculitis: Interobserver Agreement and Diagnostic Accuracy of 18F-FDG-PET/CT Wed, 28 Jan 2015 12:54:54 +0000 Introduction. 18F-FDG-PET visualises inflammation. Both atherosclerosis and giant cell arteritis cause vascular inflammation, but distinguishing the two may be difficult. The goal of this study was to assess interobserver agreement and diagnostic accuracy of 18F-FDG-PET for the detection of large artery involvement in giant cell arteritis (GCA). Methods. 31 18F-FDG-PET/CT scans were selected from 2 databases. Four observers assessed vascular wall 18F-FDG uptake, initially without and subsequently with predefined observer criteria (i.e., vascular wall 18F-FDG uptake compared to liver or femoral artery 18F-FDG uptake). External validation was performed by two additional observers. Sensitivity and specificity of 18F-FDG-PET were determined by comparing scan results to a consensus diagnosis. Results. The highest interobserver agreement (kappa: 0.96 in initial study and 0.79 in external validation) was observed when vascular wall 18F-FDG uptake higher than liver uptake was used as a diagnostic criterion, although agreement was also good without predefined criteria (kappa: 0.68 and 0.85). Sensitivity and specificity were comparable for these methods. The criterion of vascular wall 18F-FDG uptake equal to liver 18F-FDG uptake had low specificity. Conclusion. Standardization of image assessment for vascular wall 18F-FDG uptake promotes observer agreement, enables comparative studies, and does not appear to result in loss of diagnostic accuracy compared to nonstandardized assessment. K. D. F. Lensen, E. F. I. Comans, A. E. Voskuyl, C. J. van der Laken, E. Brouwer, A. T. Zwijnenburg, L. M. Pereira Arias-Bouda, A. W. J. M. Glaudemans, R. H. J. A. Slart, and Y. M. Smulders Copyright © 2015 K. D. F. Lensen et al. All rights reserved. Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation Wed, 28 Jan 2015 11:41:20 +0000 To widen the therapeutic window for PET guided evaluation of novel anti-RA agents, modifications were made in a rat model of rheumatoid arthritis (RA). Arthritis was induced in the right knee of Wistar rats with repeated boosting to prolong articular inflammation. The contralateral knee served as control. After immunization with methylated bovine serum albumin (mBSA) in complete Freund’s adjuvant and custom Bordetella pertussis antigen, one or more intra-articular (i.a.) mBSA injections were given over time in the right knee. Serum anti-mBSA antibodies, DTH response, knee thickness, motion, and synovial macrophages were analyzed and [18F]FDG(-general inflammation) and (R)-[11C]PK11195 (macrophages-)PET was performed followed by ex vivo tissue distribution. Significant anti-mBSA levels, DTH, swelling of arthritic knee, and sustained and prolonged macrophage infiltration in synovial tissue were found, especially using multiple i.a. injections. Increased [18F]FDG and (R)-[11C]PK11195 accumulation was demonstrated in arthritic knees as compared to contralateral knees, which was confirmed in ex vivo tissue distribution studies. Boosting proved advantageous for achieving a chronic model without remission. The model will offer excellent opportunities for repeated PET studies to monitor progression of disease and efficacy of novel therapeutic agents for RA in the same animal. Durga M. S. H. Chandrupatla, Karin Weijers, Yoony Y. J. Gent, Inge de Greeuw, Adriaan A. Lammertsma, Gerrit Jansen, Conny J. van der Laken, and Carla F. M. Molthoff Copyright © 2015 Durga M. S. H. Chandrupatla et al. All rights reserved. Imaging Atherosclerosis with Hybrid Positron Emission Tomography/Magnetic Resonance Imaging Wed, 28 Jan 2015 09:48:37 +0000 Noninvasive imaging of atherosclerosis could potentially move patient management towards individualized triage, treatment, and followup. The newly introduced combined positron emission tomography (PET) and magnetic resonance imaging (MRI) system could emerge as a key player in this context. Both PET and MRI have previously been used for imaging plaque morphology and function: however, the combination of the two methods may offer new synergistic opportunities. Here, we will give a short summary of current relevant clinical applications of PET and MRI in the setting of atherosclerosis. Additionally, our initial experiences with simultaneous PET/MRI for atherosclerosis imaging are presented. Finally, future potential vascular applications exploiting the unique combination of PET and MRI will be discussed. Rasmus Sejersten Ripa and Andreas Kjær Copyright © 2015 Rasmus Sejersten Ripa and Andreas Kjær. All rights reserved. Synthesis, 68Ga-Radiolabeling, and Preliminary In Vivo Assessment of a Depsipeptide-Derived Compound as a Potential PET/CT Infection Imaging Agent Wed, 28 Jan 2015 08:25:38 +0000 Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific tracers such as 67/68Ga-citrate or 18F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with 68Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia coli-bearing mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its cytotoxic and bacterial binding behaviour and compound stability, followed by 68Gallium-radiolabeling. µPET/CT using 68Ga-DOTA-TBIA101 was employed to detect muscular E. coli-infection in BALB/c mice, as warranted by the in vitro results. 68Ga-DOTA-TBIA101-PET detected E. coli-infected muscle tissue (SUV = 1.3–2.4) > noninfected thighs > forearm muscles > background in the same animal. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by renal excretion. The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not compromise the TBIA101’s capacity as targeting vector. Botshelo B. Mokaleng, Thomas Ebenhan, Suhas Ramesh, Thavendran Govender, Hendrik G. Kruger, Raveen Parboosing, Puja P. Hazari, Anil K. Mishra, Biljana Marjanovic-Painter, Jan R. Zeevaart, and Mike M. Sathekge Copyright © 2015 Botshelo B. Mokaleng et al. All rights reserved. Nuclear Medicine in Diagnosis of Prosthetic Valve Endocarditis: An Update Wed, 28 Jan 2015 07:50:23 +0000 Over the past decades cardiovascular disease management has been substantially improved by the increasing introduction of medical devices as prosthetic valves. The yearly rate of infective endocarditis (IE) in patient with a prosthetic valve is approximately 3 cases per 1,000 patients. The fatality rate of prosthetic valve endocarditis (PVE) remains stable over the years, in part due to the aging of the population. The diagnostic value of echocardiography in diagnosis is operator-dependent and its sensitivity can decrease in presence of intracardiac devices and valvular prosthesis. The modified Duke criteria are considered the gold standard for diagnosing IE; their sensibility is 80%, but in clinical practice their diagnostic accuracy in PVE is lower, resulting inconclusively in nearly 30% of cases. In the last years, these new imaging modalities have gained an increasing attention because they make it possible to diagnose an IE earlier than the structural alterations occurring. Several studies have been conducted in order to assess the diagnostic accuracy of various nuclear medicine techniques in diagnosis of PVE. We performed a review of the literature to assess the available evidence on the role of nuclear medicine techniques in the diagnosis of PVE. Maria Musso and Nicola Petrosillo Copyright © 2015 Maria Musso and Nicola Petrosillo. All rights reserved. Breast MRI in Patients with Unilateral Bloody and Serous-Bloody Nipple Discharge: A Comparison with Galactography Thu, 22 Jan 2015 13:19:11 +0000 Purpose. Assessing the role of breast MRI compared to galactography in patients with unilateral bloody or serous-bloody nipple discharge. Materials and Methods. Retrospective study including 53 unilateral discharge patients who performed galactography and MRI. We evaluated the capability of both techniques in identifying pathology and distinguishing between nonmalignant and malignant lesions. Lesions BIRADS 1/2 underwent follow-up, while the histological examination after surgery has been the gold standard to assess pathology in lesions BIRADS 3/4/5. The ROC analysis was used to test diagnostic MRI and galactography ability. Results. After surgery and follow-up, 8 patients had no disease (15%), 23 papilloma (43%), 11 papillomatosis (21%), 5 ductal cancer in situ (10%), and 6 papillary carcinoma (11%) diagnoses. Both techniques presented 100% specificity; MRI sensitivity was 98% versus 49% of galactography. Considering MRI, we found a statistical association between mass enhancement and papilloma (; AUC 0.957; CI 0.888–1.025), ductal enhancement and papillomatosis (; AUC 0.790; CI 0.623–0.958), segmental enhancement and ductal cancer in situ (; AUC 0.750; CI 0.429–1.071), and linear enhancement and papillary cancer (). Conclusions. MRI is a valid tool to detect ductal pathologies in patients with suspicious bloody or serous-bloody discharge showing higher sensitivity and specificity compared to galactography. Lucia Manganaro, Ilaria D’Ambrosio, Silvia Gigli, Francesca Di Pastena, Guglielmo Giraldi, Stefano Tardioli, Marialuisa Framarino, Lucio Maria Porfiri, and Laura Ballesio Copyright © 2015 Lucia Manganaro et al. All rights reserved. Biological Production of an Integrin αvβ3 Targeting Imaging Probe and Functional Verification Thu, 15 Jan 2015 06:30:57 +0000 The aim of the present study is to establish a bacterial clone capable of secreting an integrin αvβ3 targeting probe with bioluminescent and fluorescent activities, and to verify its specific targeting and optical activities using molecular imaging. A bacterial vector expressing a fusion of secretory Gaussia luciferase (sGluc), mCherry, and RGD (sGluc-mCherry-RGDX3; GCR), and a control vector expressing a fusion of secretory Gaussia luciferase and mCherry (sGluc-mCherry; GC) were constructed. The GCR and GC proteins were expressed in E. coli and secreted into the growth medium, which showed an approximately 10-fold higher luciferase activity than the bacterial lysate. Successful purification of GCR and GC was achieved using the 6X His-tag method. The GCR protein bound with higher affinity to U87MG cells than CHO cells in confocal microscopy and IVIS imaging, and also showed a high affinity for integrin αvβ3 expressing tumor xenografts in an in vivo animal model. An E. coli clone was established to secrete an integrin αvβ3 targeting imaging probe with bioluminescent and fluorescent activities. The probe was produced feasibly and at low cost, and has shown to be useful for the assessment of angiogenesis in vitro and in vivo. Mi-Hye Hwang, Jung Eun Kim, Sang-Yeob Kim, Senthilkumar Kalimuthu, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, and Byeong-Cheol Ahn Copyright © 2015 Mi-Hye Hwang et al. All rights reserved. Molecular Imaging: From Bench to Clinic Mon, 29 Dec 2014 08:21:49 +0000 Yì-Xiáng J. Wáng, Yongdoo Choi, Zhiyi Chen, Sophie Laurent, and Summer L. Gibbs Copyright © 2014 Yì-Xiáng J. Wáng et al. All rights reserved. Radiopharmaceuticals in Nuclear Medicine: Recent Developments for SPECT and PET Studies Sun, 21 Dec 2014 12:12:17 +0000 Bianca Gutfilen and Gianluca Valentini Copyright © 2014 Bianca Gutfilen and Gianluca Valentini. All rights reserved. Imaging Neurodegenerative Diseases: Mechanisms and Interventions Sun, 21 Dec 2014 06:10:57 +0000 Lijun Bai, Lin Ai, Mingzhou Ding, Yong He, Lixing Lao, and Fanrong Liang Copyright © 2014 Lijun Bai et al. All rights reserved. Advanced Tracers in PET Imaging of Cardiovascular Disease Wed, 15 Oct 2014 11:59:43 +0000 Cardiovascular disease is the leading cause of death worldwide. Molecular imaging with targeted tracers by positron emission tomography (PET) allows for the noninvasive detection and characterization of biological changes at the molecular level, leading to earlier disease detection, objective monitoring of therapies, and better prognostication of cardiovascular diseases progression. Here we review, the current role of PET in cardiovascular disease, with emphasize on tracers developed for PET imaging of cardiovascular diseases. Yesen Li, Wei Zhang, Hua Wu, and Gang Liu Copyright © 2014 Yesen Li et al. All rights reserved. H-CRRETAWAC-OH, a Lead Structure for the Development of Radiotracer Targeting Integrin α5β1? Mon, 13 Oct 2014 14:04:26 +0000 Imaging of angiogenic processes is of great interest in preclinical research as well as in clinical settings. The most commonly addressed target structure for imaging angiogenesis is the integrin αvβ3. Here we describe the synthesis and evaluation of [18F]FProp--Arg-Arg-Glu-Thr-Ala-Trp-Ala--OH, a radiolabelled peptide designed to selectively target the integrin α5β1. Conjugation of 4-nitrophenyl-(RS)-2-[18F]fluoropropionate provided [18F]FProp--Arg-Arg-Glu-Thr-Ala-Trp-Ala--OH in high radiochemical purity (>95%) and a radiochemical yield of approx. 55%. In vitro evaluation showed α5β1 binding affinity in the nanomolar range, whereas affinity to αvβ3 and αIIbβ3 was >50 μM. Cell uptake studies using human melanoma M21 (αvβ3-positive and α5β1-negative), human melanoma M21-L (αvβ3-negative and α5β1-negative), and human prostate carcinoma DU145 (αvβ3-negative and α5β1-positive) confirmed receptor-specific binding. The radiotracer was stable in human serum and showed low protein binding. Biodistribution studies showed tumour uptake ranging from 2.5 to 3.5% ID/g between 30 and 120 min post-injection. However, blocking studies and studies using mice bearing α5β1-negative M21 tumours did not confirm receptor-specific uptake of [18F]FProp--Arg-Arg-Glu-Thr-Ala-Trp-Ala--OH, although this radiopeptide revealed high affinity and substantial selectivity to α5β1 in vitro. Further experiments are needed to study the in vivo metabolism of this peptide and to develop improved radiopeptide candidates suitable for PET imaging of α5β1 expression in vivo. Roland Haubner, Simone Maschauer, Jürgen Einsiedel, Iris E. Eder, Christine Rangger, Peter Gmeiner, Irene J. Virgolini, and Olaf Prante Copyright © 2014 Roland Haubner et al. All rights reserved. 18FDG, [18F]FLT, [18F]FAZA, and 11C-Methionine Are Suitable Tracers for the Diagnosis and In Vivo Follow-Up of the Efficacy of Chemotherapy by miniPET in Both Multidrug Resistant and Sensitive Human Gynecologic Tumor Xenografts Thu, 18 Sep 2014 05:25:40 +0000 Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG), 11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), and [18F]fluoroazomycin-arabinofuranoside (18FAZA) for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+) and negative (Pgp−) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+ and Pgp− A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+ tumors. Our results demonstrate that 18FDG, 18F-FLT, 18FAZA, and 11C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp+ and Pgp− human tumor xenografts by miniPET. György Trencsényi, Teréz Márián, Imre Lajtos, Zoltán Krasznai, László Balkay, Miklós Emri, Pál Mikecz, Katalin Goda, Gábor Szalóki, István Juhász, Enikő Németh, Tünde Miklovicz, Gábor Szabó, and Zoárd T. Krasznai Copyright © 2014 György Trencsényi et al. All rights reserved. The Longitudinal Assessment of Osteomyelitis Development by Molecular Imaging in a Rabbit Model Thu, 11 Sep 2014 05:50:17 +0000 Introduction. Osteomyelitis is a severe orthopaedic complication which is difficult to diagnose and treat. Previous experimental studies mainly focussed on evaluating osteomyelitis in the presence of an implant or used a sclerosing agent to promote infection onset. In contrast, we focused on the longitudinal assessment of a nonimplant related osteomyelitis. Methods. An intramedullary tibial infection with S. aureus was established in NZW rabbits. Clinical and haematological infection status was evaluated weekly, combined with X-ray radiographs, biweekly injections of calcium binding fluorophores, and postmortem micro-CT. The development of the infection was assessed by micro-PET at consecutive time points using 18F-FDG as an infection tracer. Results. The intramedullary contamination of the rabbit tibia resulted in an osteomyelitis. Haematological parameters confirmed infection in mainly the first postoperative weeks (CRP at the first 5 postoperative weeks, leucocyte differentiation at the second and sixth postoperative weeks, and ESR on the second postoperative week only), while micro-PET was able to detect the infection from the first post-operative week onward until the end of the study. Conclusions. This study shows that osteomyelitis in the rabbit can be induced without use of an implant or sclerosing agent. The sequential follow-up indicates that the diagnostic value of each infection parameter is time point dependant. Furthermore, from all parameters used, the diagnostic value of  18F-FDG micro-PET is the most versatile to assess the presence of an orthopaedic infection in this model. Jim C. E. Odekerken, Geert H. I. M. Walenkamp, Boudewijn T. Brans, Tim J. M. Welting, and Jacobus J. C. Arts Copyright © 2014 Jim C. E. Odekerken et al. All rights reserved. Giant Cell Arteritis: A Systematic Review of the Qualitative and Semiquantitative Methods to Assess Vasculitis with 18F-Fluorodeoxyglucose Positron Emission Tomography Mon, 01 Sep 2014 12:16:34 +0000 Giant cell arteritis (GCA) is the most common vasculitis affecting medium and large vessels. It shows a close clinical association with polymyalgia rheumatica (PMR), a musculoskeletal inflammatory disorder, which is clinically characterized by girdles pain and stiffness. 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is an effective tool for the diagnosis, grading, and follow-up of patients affected by GCA involving the aorta and its proximal branches, but the lack of a standardized method for the assessment of vascular inflammation remains a critical issue, potentially leading to misclassification. In our systematic review, including 19 original articles for a total of 442 GCA patients (with or without PMR symptoms) and 535 healthy controls, we described the different qualitative, semiquantitative and combined methods that have been proposed throughout the literature for assessing the presence and grading the severity of GCA-related vascular inflammation on 18F-FDG PET scans, focusing on the diagnostic performance and examining their respective advantages and limitations. The majority of the included studies adopted qualitative methods of PET image analysis, which are less sensitive but more specific than semiquantitative ones. Among the semiquantitative approaches, the aortic-to-blood pool uptake ratio of the aortic arch seems to be the most accurate method. Cristina Puppo, Michela Massollo, Francesco Paparo, Dario Camellino, Arnoldo Piccardo, Mehrdad Shoushtari Zadeh Naseri, Giampiero Villavecchia, Gian Andrea Rollandi, and Marco Amedeo Cimmino Copyright © 2014 Cristina Puppo et al. All rights reserved. Synthesis and Preclinical Characterization of [18F]FPBZA: A Novel PET Probe for Melanoma Mon, 01 Sep 2014 08:04:17 +0000 Introduction. Benzamide can specifically bind to melanoma cells. A 18F-labeled benzamide derivative, [18F]N-(2-diethylaminoethyl)-4-[2-(2-(2-fluoroethoxy) ethoxy)ethoxy]benzamide ([18F]FPBZA), was developed as a promising PET probe for primary and metastatic melanoma. Methods. [18F]FPBZA was synthesized via a one-step radiofluorination in this study. The specific uptake of [18F]FPBZA was studied in B16F0 melanoma cells, A375 amelanotic melanoma cells, and NB-DNJ-pretreated B16F0 melanoma cells. The biological characterization of [18F]FPBZA was performed on mice bearing B16F0 melanoma, A375 amelanotic melanoma, or inflammation lesion. Results. [18F]FPBZA can be prepared efficiently with a yield of 40–50%. The uptake of [18F]FPBZA by B16F0 melanoma cells was significantly higher than those by A375 tumor cells and NB-DNJ-pretreated B16F0 melanoma cells. B16F0 melanoma displayed prominent uptake of [18F]FPBZA at 2 h ( %ID/g), compared with A375 tumor and inflammation lesion ( and  %ID/g, resp.). [18F]FPBZA microPET scan clearly delineated B16F0 melanoma but not A375 tumor and inflammation lesion. In mice bearing pulmonary metastases, the lung radioactivity reached  %ID/g at 2 h (versus  %ID/g in normal mice). Conclusions. Our results suggested that [18F]FPBZA PET would provide a promising and specific approach for the detection of primary and metastatic melanoma lesions. Shih-Yen Wu, Shih-Pin Huang, Yen-Chen Lo, Ren-Shyan Liu, Shyh-Jen Wang, Wuu-Jyh Lin, Chih-Chieh Shen, and Hsin-Ell Wang Copyright © 2014 Shih-Yen Wu et al. All rights reserved. Assessment of Cardiac Sarcoidosis with Advanced Imaging Modalities Thu, 28 Aug 2014 15:28:03 +0000 Sarcoidosis is a chronic systemic disease of unknown etiology that is characterized by the presence of noncaseating epithelioid granulomas, usually in multiple organs. Several studies have shown that sarcoidosis might be the result of an exaggerated granulomatous reaction after exposure to unidentified antigens in genetically susceptible individuals. Cardiac involvement may occur and lead to an adverse outcome: the heart mechanics will be affected and that causes ventricular failure, and the cardiac electrical system will be disrupted and lead to third degree atrioventricular block, malignant ventricular tachycardia, and sudden cardiac death. Thus, early diagnosis and treatment of this potentially devastating disease is critically important. However, sensitive and accurate imaging modalities have not been established. Recent studies have demonstrated the promising potential of cardiac magnetic resonance imaging (MRI) and 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) in the diagnosis and assessment of cardiac sarcoidosis (CS). In this review, we discuss the epidemiology, etiology, histological findings, and clinical features of sarcoidosis. We also introduce advanced imaging including 18F-FDG PET and cardiac MRI as more reliable diagnostic modalities for CS. Makoto Orii, Toshio Imanishi, and Takashi Akasaka Copyright © 2014 Makoto Orii et al. All rights reserved. Antimicrobial Peptides: Their Role as Infection-Selective Tracers for Molecular Imaging Wed, 27 Aug 2014 09:07:27 +0000 Antimicrobial peptides (AMPs) are a heterogeneous class of compounds found in a variety of organisms including humans and, so far, hundreds of these structures have been isolated and characterised. They can be described as natural microbicide, selectively cytotoxic to bacteria, whilst showing minimal cytotoxicity towards the mammalian cells of the host organism. They act by their relatively strong electrostatic attraction to the negatively charged bacterial cells and a relatively weak interaction to the eukaryote host cells. The ability of these peptides to accumulate at sites of infection combined with the minimal host’s cytotoxicity motivated for this review to highlight the role and the usefulness of AMPs for PET with emphasis on their mechanism of action and the different interactions with the bacterial cell. These details are key information for their selective properties. We also describe the strategy, design, and utilization of these peptides as potential radiopharmaceuticals as their combination with nuclear medicine modalities such as SPECT or PET would allow noninvasive whole-body examination for detection of occult infection causing, for example, fever of unknown origin. Thomas Ebenhan, Olivier Gheysens, Hendrick Gert Kruger, Jan Rijn Zeevaart, and Mike Machaba Sathekge Copyright © 2014 Thomas Ebenhan et al. All rights reserved. 18F-Fluorodeoxyglucose Positron Emission Tomography/CT Scanning in Diagnosing Vascular Prosthetic Graft Infection Tue, 19 Aug 2014 07:06:59 +0000 Vascular prosthetic graft infection (VPGI) is a severe complication after vascular surgery. CT-scan is considered the diagnostic tool of choice in advanced VPGI. The incidence of a false-negative result using CT is relatively high, especially in the presence of low-grade infections. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scanning has been suggested as an alternative for the diagnosis and assessment of infectious processes. Hybrid 18F-FDG PET/CT has established the role of 18F-FDG PET for the assessment of suspected VPGI, providing accurate anatomic localization of the site of infection. However, there are no clear guidelines for the interpretation of the uptake patterns of 18F-FDG as clinical tool for VPGI. Based on the available literature it is suggested that a linear, diffuse, and homogeneous uptake should not be regarded as an infection whereas focal or heterogeneous uptake with a projection over the vessel on CT is highly suggestive of infection. Nevertheless, 18F-FDG PET and 18F-FDG PET/CT can play an important role in the detection of VPGI and monitoring response to treatment. However an accurate uptake and pattern recognition is warranted and cut-off uptake values and patterns need to be standardized before considering the technique to be the new standard. Ben R. Saleem, Robert A. Pol, Riemer H. J. A. Slart, Michel M. P. J. Reijnen, and Clark J. Zeebregts Copyright © 2014 Ben R. Saleem et al. All rights reserved. Hepatosplenic Sarcoidosis: Contrast-Enhanced Ultrasound Findings and Implications for Clinical Practice Mon, 18 Aug 2014 09:13:36 +0000 Sarcoidosis is a complex granulomatous disease that affects virtually every organ and tissue, with a prevalence that varies significantly among the sites involved. The role of conventional imaging, such as computed tomography and magnetic resonance imaging, in the assessment of hepatosplenic sarcoidosis is well established by revealing organ enlargement, multiple discrete nodules, and lymphadenopathy. In this review, we aim to describe contrast-enhanced ultrasound (CEUS) findings in liver and spleen involvement by sarcoidosis, reporting evidence from the literature and cases from our experience, after a brief update on safety profile, cost-effectiveness, and clinical indications of this novel technique. Furthermore, we highlight potential advantages of CEUS in assessing hepatosplenic sarcoidosis that may be useful in the clinical practice. Claudio Tana, Christoph F. Dietrich, and Cosima Schiavone Copyright © 2014 Claudio Tana et al. All rights reserved. Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers Sun, 17 Aug 2014 11:12:56 +0000 With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers. Qiu-Lan Zhou, Zhi-Yi Chen, Yi-Xiang Wang, Feng Yang, Yan Lin, and Yang-Ying Liao Copyright © 2014 Qiu-Lan Zhou et al. All rights reserved. The Role of 18F-FDG PET/CT in Large-Vessel Vasculitis: Appropriateness of Current Classification Criteria? Thu, 14 Aug 2014 09:04:43 +0000 Patients with clinical suspicion of large-vessel vasculitis (LVV) may present with nonspecific signs and symptoms and increased inflammatory parameters and may remain without diagnosis after routine diagnostic procedures. Both the nonspecificity of the radiopharmaceutical 18F-FDG and the synergy of integrating functional and anatomical images with PET/CT offer substantial benefit in the diagnostic work-up of patients with clinical suspicion for LVV. A negative temporal artery biopsy, an ultrasonography without an arterial halo, or a MRI without aortic wall thickening or oedema do not exclude the presence of LVV and should therefore not exclude the use of 18F-FDG PET/CT when LVV is clinically suspected. This overview further discusses the notion that there is substantial underdiagnosis of LVV. Late diagnosis of LVV may lead to surgery or angioplasty in occlusive forms and is often accompanied by serious aortic complications and a fatal outcome. In contrast to the American College of Rheumatology 1990 criteria for vasculitis, based on late LVV effects like arterial stenosis and/or occlusion, 18F-FDG PET/CT sheds new light on the classification of giant cell arteritis (GCA) and Takayasu arteritis (TA). The combination of these observations makes the role of 18F-FDG PET/CT in the assessment of patients suspected for having LVV promising. H. Balink, R. J. Bennink, B. L. F. van Eck-Smit, and H. J. Verberne Copyright © 2014 H. Balink et al. All rights reserved. Erratum to “Biodistribution and SPECT Imaging Study of Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma” Tue, 05 Aug 2014 11:07:16 +0000 Wenhui Ma, Zhe Wang, Weidong Yang, Xiaowei Ma, Fei Kang, and Jing Wang Copyright © 2014 Wenhui Ma et al. All rights reserved. Recent Trends in Pharmaceutical Radiochemistry for Molecular PET Imaging Thu, 24 Jul 2014 10:27:22 +0000 Olaf Prante, Roland Haubner, Patrick Riss, and Bernd Neumaier Copyright © 2014 Olaf Prante et al. All rights reserved. 18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals Thu, 24 Jul 2014 00:00:00 +0000 Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET). These “nonclassical” labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F) to either an aliphatic or aromatic carbon atom. One method in particular, the silicon-fluoride-acceptor isotopic exchange (SiFA-IE) approach, invalidates a dogma in radiochemistry that has been widely accepted for many years: the inability to obtain radiopharmaceuticals of high specific activity (SA) via simple IE. Methodology. The most advantageous feature of IE labeling in general is that labeling precursor and labeled radiotracer are chemically identical, eliminating the need to separate the radiotracer from its precursor. SiFA-IE chemistry proceeds in dipolar aprotic solvents at room temperature and below, entirely avoiding the formation of radioactive side products during the IE. Scope of Review. A great plethora of different SiFA species have been reported in the literature ranging from small prosthetic groups and other compounds of low molecular weight to labeled peptides and most recently affibody molecules. Conclusions. The literature over the last years (from 2006 to 2014) shows unambiguously that SiFA-IE and other silicon-based fluoride acceptor strategies relying on 18F− leaving group substitutions have the potential to become a valuable addition to radiochemistry. Vadim Bernard-Gauthier, Carmen Wängler, Esther Schirrmacher, Alexey Kostikov, Klaus Jurkschat, Bjoern Wängler, and Ralf Schirrmacher Copyright © 2014 Vadim Bernard-Gauthier et al. All rights reserved. Evaluation of Growth Patterns and Body Composition in C57Bl/6J Mice Using Dual Energy X-Ray Absorptiometry Thu, 10 Jul 2014 12:21:13 +0000 The normal growth pattern of female C57BL/6J mice, from 5 to 30 weeks of age, has been investigated in a longitudinal study. Weight, body surface area (BS), and body mass index (BMI) were evaluated in forty mice. Lean mass and fat mass, bone mineral content (BMC), and bone mineral density (BMD) were monitored by dual energy X-ray absorptiometry (DEXA). Weight and BS increased linearly ( g;  cm2, ), more markedly from 5 to 9 weeks of age . BMD showed a peak at 17 weeks ( g/cm2 m, ). Lean mass showed an evident gain at 9 ( g, ) and 25 weeks ( g, ), like fat mass from 13 to 17 weeks ( g, ). BMI and lean mass index (LMI) reached the highest value at 21 weeks ( g/cm2, resp.), like fat mass index (FMI) at 17 weeks ( g/cm2) (). BMI, weight, and BS showed a moderate positive correlation (0.45–0.85) with lean mass from 5 to 21 weeks. Mixed linear models provided a good prediction for lean mass, fat mass, and BMD. This study may represent a baseline reference for a future comparison of wild-type C57BL/6J mice with models of altered growth. Sara Gargiulo, Matteo Gramanzini, Rosario Megna, Adelaide Greco, Sandra Albanese, Claudio Manfredi, and Arturo Brunetti Copyright © 2014 Sara Gargiulo et al. All rights reserved. Radiosynthesis of [18F]Trifluoroalkyl Groups: Scope and Limitations Thu, 10 Jul 2014 12:07:29 +0000 The present paper is concerned with radiochemical methodology to furnish the trifluoromethyl motif labelled with 18F. Literature spanning the last four decades is comprehensively reviewed and radiochemical yields and specific activities are discussed. V. T. Lien and P. J. Riss Copyright © 2014 V. T. Lien and P. J. Riss. All rights reserved. New Acquisition Protocol of 18F-Choline PET/CT in Prostate Cancer Patients: Review of the Literature about Methodology and Proposal of Standardization Thu, 10 Jul 2014 00:00:00 +0000 Purpose. (1) To evaluate a new acquisition protocol of 18F-choline (FCH) PET/CT for prostate cancer patients (PC), (2) to review acquisition 18F-choline PET/CT methodology, and (3) to propose a standardized acquisition protocol on FCH PET/CT in PC patients. Materials. 100 consecutive PC patients (mean age 70.5 years, mean PSA 21.35 ng/mL) were prospectively evaluated. New protocol consisted of an early scan of the pelvis immediately after the injection of the tracer (1 bed position of 4 min) followed by a whole body scan at one 1 hour. Early and 1 hour images were compared for interfering activity and pathologic findings. Results. The overall detection rate of FCH PET/CT was 64%. The early static images of the pelvis showed absence of radioactive urine in ureters, bladder, or urethra which allowed a clean evaluation of the prostatic fossae. Uptake in the prostatic region was better visualized in the early phase in 26% (7/30) of cases. Other pelvic pathologic findings (bone and lymph nodes) were visualized in both early and late images. Conclusion. Early 18F-choline images improve visualization of abnormal uptake in prostate fossae. All pathologic pelvic deposits (prostate, lymph nodes, and bone) were visualized in both early and late images. Sotirios Chondrogiannis, Maria Cristina Marzola, Gaia Grassetto, Anna Margherita Maffione, Lucia Rampin, Emma Veronese, Arianna Massaro, and Domenico Rubello Copyright © 2014 Sotirios Chondrogiannis et al. All rights reserved. Magnetic Resonance Spectroscopy in the Diagnosis of Dementia with Lewy Bodies Sun, 06 Jul 2014 06:14:56 +0000 Dementia with Lewy bodies (DLB) is considered to be the second most frequent primary degenerative dementing illness after Alzheimer’s disease (AD). DLB, together with Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) belong to α-synucleinopathies—a group of neurodegenerative diseases associated with pathological accumulation of the α-synuclein protein. Dementia due to PD and DLB shares clinical symptoms and neuropsychological profiles. Moreover, the core features and additional clinical signs and symptoms for these two very similar diseases are largely the same. Neuroimaging seems to be a promising method in differential diagnosis of dementia studies. The development of imaging methods or other objective measures to supplement clinical criteria for DLB is needed and a method which would accurately facilitate diagnosis of DLB prior to death is still being searched. Proton magnetic resonance spectroscopy (1H-MRS) provides a noninvasive method of assessing an in vivo biochemistry of brain tissue. This review summarizes the main results obtained from the application of neuroimaging techniques in DLB cases focusing on 1H-MRS. Radoslaw Magierski and Tomasz Sobow Copyright © 2014 Radoslaw Magierski and Tomasz Sobow. All rights reserved. Side of Limb-Onset Predicts Laterality of Gray Matter Loss in Amyotrophic Lateral Sclerosis Tue, 01 Jul 2014 12:25:55 +0000 Conflicting findings have been reported regarding the lateralized brain abnormality in patients with amyotrophic lateral sclerosis (ALS). In this study, we aimed to investigate the probable lateralization of gray matter (GM) atrophy in ALS patients. We focused on the relationship between the asymmetry in decreased GM volume and the side of disease onset in patients with limb-onset. Structural imaging evaluation of normalized atrophy (SIENAX) and voxel-based morphometry (VBM) were used to assess differences in global and local brain regions in patients with heterogeneous body onset and subgroups with different side of limb-onset. We found global brain atrophy and GM losses in the frontal and parietal areas in each patient group as well as left predominant GM losses in the total cohort. The intriguing findings in subgroup analyses demonstrated that the motor cortex in the contralateral hemisphere of the initially involved limb was most affected. We also found that regional brain atrophy was related to disease progression rate. Our observations suggested that side of limb-onset can predict laterality of GM loss in ALS patients and disease progression correlates with the extent of cortical abnormality. Qiuli Zhang, Cuiping Mao, Jiaoting Jin, Chen Niu, Lijun Bai, Jingxia Dang, and Ming Zhang Copyright © 2014 Qiuli Zhang et al. All rights reserved. Radiation Absorbed Dose to the Basal Ganglia from Dopamine Transporter Radioligand 18F-FPCIT Mon, 30 Jun 2014 00:00:00 +0000 Our previous dosimetry studies have demonstrated that for dopaminergic radiotracers, 18F-FDOPA and 18F-FPCIT, the urinary bladder is the critical organ. As these tracers accumulate in the basal ganglia (BG) with high affinity and long residence times, radiation dose to the BG may become significant, especially in normal control subjects. We have performed dynamic PET measurements using 18F-FPCIT in 16 normal adult subjects to determine if in fact the BG, although not a whole organ, but a well-defined substructure, receives the highest dose. Regions of interest were drawn over left and right BG structures. Resultant time-activity curves were generated and used to determine residence times for dosimetry calculations. -factors were computed using the MIRDOSE3 nodule model for each caudate and putamen. For 18F-FPCIT, BG dose ranged from 0.029 to 0.069 mGy/MBq. In half of all subjects, BG dose exceeded 85% of the published critical organ (bladder) dose, and in three of those, the BG dose exceeded that for the bladder. The BG can become the dose-limiting organ in studies using dopamine transporter ligands. For some normal subjects studied with F-18 or long half-life radionuclide, the BG may exceed bladder dose and become the critical structure. William Robeson, Vijay Dhawan, Yilong Ma, David Bjelke, Claude Margouleff, Thomas Chaly, and David Eidelberg Copyright © 2014 William Robeson et al. All rights reserved. A Comparison between Gadofosveset Trisodium and Gadobenate Dimeglumine for Steady State MRA of the Thoracic Vasculature Sun, 29 Jun 2014 11:38:49 +0000 Purpose. Retrospective comparison between gadofosveset trisodium and gadobenate dimeglumine steady state magnetic resonance angiography (SS-MRA) of the thoracic vasculature at 1.5T using signal-to-noise ratio (SNR) and vessel edge sharpness (ES) as markers of image quality. Materials and Methods. IRB approval was obtained. Twenty separate patients each underwent SS-MRA using high-resolution 3D ECG-triggered coronal IR-TFE at 1.5T approximately 3-4 minutes following 10 or 15 mL gadofosveset or 20 mL gadobenate. ROIs were placed in the right atrium, left ventricle, left atrium, ascending aorta, descending aorta, and right pulmonary artery to estimate SNR. Vessel ES was estimated as 20–80% rise distances from line intensity profiles in the left pulmonary vein, ascending aorta, and descending aorta. Data were analyzed using nonpaired Student’s -test (threshold for significance set at ). Results. There was no significant difference in mean SNR for the gadofosveset or gadobenate groups ( values: 0.14 to 0.85). There was no significant difference in mean vessel ES for gadofosveset and gadobenate groups ( values: 0.17 to 0.78). Conclusion. High quality thoracic SS-MRA can be achieved with gadobenate dimeglumine, similar to that achieved with the blood pool agent gadofosveset trisodium provided that imaging is initiated quickly (3-4 min) after contrast injection. G. Paul Camren, Gregory J. Wilson, Vikram R. Bamra, Khahn Q. Nguyen, Daniel S. Hippe, and Jeffrey H. Maki Copyright © 2014 G. Paul Camren et al. All rights reserved. 18F-Labelled Intermediates for Radiosynthesis by Modular Build-Up Reactions: Newer Developments Mon, 23 Jun 2014 06:53:10 +0000 This brief review gives an overview of newer developments in 18F-chemistry with the focus on small 18F-labelled molecules as intermediates for modular build-up syntheses. The short half-life (<2 h) of the radionuclide requires efficient syntheses of these intermediates considering that multistep syntheses are often time consuming and characterized by a loss of yield in each reaction step. Recent examples of improved synthesis of 18F-labelled intermediates show new possibilities for no-carrier-added ring-fluorinated arenes, novel intermediates for tri[18F]fluoromethylation reactions, and 18F-fluorovinylation methods. Johannes Ermert Copyright © 2014 Johannes Ermert. All rights reserved. PET Radiopharmaceuticals for Imaging Integrin Expression: Tracers in Clinical Studies and Recent Developments Wed, 11 Jun 2014 12:08:49 +0000 Noninvasive determination of integrin expression has become an interesting approach in nuclear medicine. Since the discovery of the first 18F-labeled cyclic RGD peptide as radiotracer for imaging integrin expression in vivo, there have been carried out enormous efforts to develop RGD peptides for PET imaging. Moreover, in recent years, additional integrins, including and , came into the focus of pharmaceutical radiochemistry. This review will discuss the tracers already evaluated in clinical trials and summarize the preliminary outcome. It will also give an overview on recent developments to further optimize the first-generation compounds such as [18F]Galacto-RGD. This includes recently developed 18F-labeling strategies and also new approaches in 68Ga-complex chemistry. Furthermore, the approaches to develop radiopharmaceuticals targeting integrin and will be summarized and discussed. Roland Haubner, Simone Maschauer, and Olaf Prante Copyright © 2014 Roland Haubner et al. All rights reserved. Erratum to “A Survey of FDG- and Amyloid-PET Imaging in Dementia and GRADE Analysis” Wed, 11 Jun 2014 09:30:07 +0000 Daniela Perani, Orazio Schillaci, Alessandro Padovani, Flavio Mariano Nobili, Leonardo Iaccarino, Pasquale Anthony Della Rosa, Giovanni Frisoni, and Carlo Caltagirone Copyright © 2014 Daniela Perani et al. All rights reserved. Preliminary Clinical Experience of trans-1-Amino-3-(18)F-fluorocyclobutanecarboxylic Acid (anti-(18)F-FACBC) PET/CT Imaging in Prostate Cancer Patients Sun, 01 Jun 2014 13:27:22 +0000 Background. In this retrospective analysis we assessed the role of [18F]-FACBC-PET/CT in the prostatic cancer staging. Procedure. 30 first [18F]-FACBC-PET/CT images of 26 patients (68.1 ± 5.8 years) were analyzed. PET/CT findings were compared with PSA concentrations, with PSA doubling times (PDT), and with correlative imaging. Results. On 16 [18F]-FACBC (53.3%) scans, 58 metabolically active lesions were found. 12 (20.7%) lesions corresponding to the local relapse were found in prostate/prostate bed and seminal vesicles, 9 (15.5%) lesions were located in regional lymph nodes, 10 (17.2%) were located in distal lymph nodes, and 26 (44.8%) metabolically active lesions were found in the skeleton. In one case, focal uptake was found in the brain, confirmed further on MRI as meningioma. The mean S-PSA level in patients with positive [18F]-FACBC findings was 9.5 ± 16.9 μg/L (0.54–69 μg/L) and in patients with negative [18F]-FACBC findings was 1.96 ± 1.87 μg/L (0.11–5.9 μg/L), but the difference was not statistically significant. However, the PSA doubling time (PDT) in patients with positive findings was significantly shorter than PDT in patients with negative findings: 3.25 ± 2.09 months (0.3–6 months) versus 31.2 ± 22.02 months (8–84 months), . There was a strong positive correlation between PSA value and number of metabolically active lesions () and a negative correlation between PDT and number of metabolically active lesions (). There was a weak negative correlation between PDT and (). Conclusion. According to our preliminary clinical experience, [18F]-FACBC-PET may play a role in in vivo restaging of an active prostate cancer, especially in patients with a short S-PSA doubling time. Kalevi Kairemo, Nigora Rasulova, Kaarina Partanen, and Timo Joensuu Copyright © 2014 Kalevi Kairemo et al. All rights reserved. Sweetening Pharmaceutical Radiochemistry by 18F-Fluoroglycosylation: A Short Review Sun, 01 Jun 2014 08:17:08 +0000 At the time when the highly efficient [18F]FDG synthesis was discovered by the use of the effective precursor 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose (mannose triflate) for nucleophilic 18F-substitution, the field of PET in nuclear medicine experienced a long-term boom. Thirty years later, various strategies for chemoselective 18F-labeling of biomolecules have been developed, trying to keep up with the emerging field of radiopharmaceutical sciences. Among the new radiochemical strategies, chemoselective 18F-fluoroglycosylation methods aim at the sweetening of pharmaceutical radiochemistry by providing a powerful and highly valuable tool for the design of 18F-glycoconjugates with suitable in vivo properties for PET imaging studies. This paper provides a short review (reflecting the literature not older than 8 years) on the different 18F-fluoroglycosylation reactions that have been applied to the development of various 18F-glycoconjugate tracers, including not only peptides, but also nonpeptidic tracers and high-molecular-weight proteins. Simone Maschauer and Olaf Prante Copyright © 2014 Simone Maschauer and Olaf Prante. All rights reserved. Molecular Image-Guided Theranostic and Personalized Medicine 2013 Thu, 29 May 2014 08:33:07 +0000 Hong Zhang, Mei Tian, Ignasi Carrio, Ali Cahid Civelek, and Yasuhisa Fujibayashi Copyright © 2014 Hong Zhang et al. All rights reserved. 6-[18F]Fluoro-L-DOPA: A Well-Established Neurotracer with Expanding Application Spectrum and Strongly Improved Radiosyntheses Wed, 28 May 2014 08:47:18 +0000 For many years, the main application of [18F]F-DOPA has been the PET imaging of neuropsychiatric diseases, movement disorders, and brain malignancies. Recent findings however point to very favorable results of this tracer for the imaging of other malignant diseases such as neuroendocrine tumors, pheochromocytoma, and pancreatic adenocarcinoma expanding its application spectrum. With the application of this tracer in neuroendocrine tumor imaging, improved radiosyntheses have been developed. Among these, the no-carrier-added nucleophilic introduction of fluorine-18, especially, has gained increasing attention as it gives [18F]F-DOPA in higher specific activities and shorter reaction times by less intricate synthesis protocols. The nucleophilic syntheses which were developed recently are able to provide [18F]F-DOPA by automated syntheses in very high specific activities, radiochemical yields, and enantiomeric purities. This review summarizes the developments in the field of [18F]F-DOPA syntheses using electrophilic synthesis pathways as well as recent developments of nucleophilic syntheses of [18F]F-DOPA and compares the different synthesis strategies regarding the accessibility and applicability of the products for human in vivo PET tumor imaging. M. Pretze, C. Wängler, and B. Wängler Copyright © 2014 M. Pretze et al. All rights reserved. Zirconium-89 Labeled Antibodies: A New Tool for Molecular Imaging in Cancer Patients Wed, 28 May 2014 08:19:12 +0000 Antibody based positron emission tomography (immuno-PET) imaging is of increasing importance to visualize and characterize tumor lesions. Additionally, it can be used to identify patients who may benefit from a particular therapy and monitor the therapy outcome. In recent years the field is focused on 89Zr, a radiometal with near ideal physical and chemical properties for immuno-PET. In this review we will discuss the production of  89Zr, the bioconjugation strategies, and applications in (pre-)clinical studies of  89Zr-based immuno-PET in oncology. To date, 89Zr-based PET imaging has been investigated in a wide variety of cancer-related targets. Moreover, clinical studies have shown the feasibility for 89Zr-based immuno-PET to predict and monitor treatment, which could be used to tailor treatment for the individual patient. Further research should be directed towards the development of standardized and robust conjugation methods and improved chelators to minimize the amount of released Zr4+ from the antibodies. Additionally, further validation of the imaging method is required. The ongoing development of new 89Zr-labeled antibodies directed against novel tumor targets is expected to expand applications of  89Zr-labeled immuno-PET to a valuable method in the medical imaging. Floor C. J. van de Watering, Mark Rijpkema, Lars Perk, Ulrich Brinkmann, Wim J. G. Oyen, and Otto C. Boerman Copyright © 2014 Floor C. J. van de Watering et al. All rights reserved. 18F-Labeling Using Click Cycloadditions Tue, 27 May 2014 06:21:50 +0000 Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 ( min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of 18F in those molecules poses an exceeding challenge. Two major challenges during 18F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel 18F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click 18F-cycloadditions. Kathrin Kettenbach, Hanno Schieferstein, and Tobias L. Ross Copyright © 2014 Kathrin Kettenbach et al. All rights reserved. Corticospinal Tract Change during Motor Recovery in Patients with Medulla Infarct: A Diffusion Tensor Imaging Study Sun, 25 May 2014 08:06:41 +0000 Diffusion tensor imaging (DTI) and tractography (DTT) provide a powerful vehicle for investigating motor recovery mechanisms. However, little is known about these mechanisms in patients with medullary lesions. We used DTI and DTT to evaluate three patients presenting with motor deficits following unilateral medulla infarct. Patients were scanned three times during 1 month (within 7, 14, and 30 days after stroke onset). Fractional anisotropy (FA) values were measured in the medulla, cerebral peduncle, and internal capsule. The three-dimensional corticospinal tract (CST) was reconstructed using DTT. Patients 1 and 2 showed good motor recovery after 14 days, and the FA values of their affected CST were slightly decreased. DTTs demonstrated that the affected CST passed along periinfarct areas and that tract integrity was preserved in the medulla. Patient 3 had the most obvious decrease in FA values along the affected CST, with motor deficits of the right upper extremity after 30 days. The affected CST passed through the infarct and was disrupted in the medulla. In conclusion, DTI can detect the involvement and changes of the CST in patients with medulla infarct during motor recovery. The degree of degeneration and spared periinfarct CST compensation may be an important motor recovery mechanism. Dongdong Rong, Miao Zhang, Qingfeng Ma, Jie Lu, and Kuncheng Li Copyright © 2014 Dongdong Rong et al. All rights reserved. Radiopharmaceutical Stem Cell Tracking for Neurological Diseases Sun, 25 May 2014 06:41:51 +0000 Although neurological ailments continue to be some of the main causes of disease burden in the world, current therapies such as pharmacological agents have limited potential in the restoration of neural functions. Cell therapies, firstly applied to treat different hematological diseases, are now being investigated in preclinical and clinical studies for neurological illnesses. However, the potential applications and mechanisms for such treatments are still poorly comprehended and are the focus of permanent research. In this setting, noninvasive in vivo imaging allows better understanding of several aspects of stem cell therapies. Amongst the various methods available, radioisotope cell labeling has become one of the most promising since it permits tracking of cells after injection by different routes to investigate their biodistribution. A significant increase in the number of studies utilizing this method has occurred in the last years. Here, we review the different radiopharmaceuticals, imaging techniques, and findings of the preclinical and clinical reports published up to now. Moreover, we discuss the limitations and future applications of radioisotope cell labeling in the field of cell transplantation for neurological diseases. Paulo Henrique Rosado-de-Castro, Pedro Moreno Pimentel-Coelho, Bianca Gutfilen, Sergio Augusto Lopes de Souza, Gabriel Rodriguez de Freitas, Rosalia Mendez-Otero, and Lea Mirian Barbosa da Fonseca Copyright © 2014 Paulo Henrique Rosado-de-Castro et al. All rights reserved. CEUS Helps to Rerate Small Breast Tumors of BI-RADS Category 3 and Category 4 Sun, 25 May 2014 06:03:22 +0000 Purpose. The primary aim of this study was to explore if classification, whether using the BI-RADS categories based on CEUS or conventional ultrasound, was conducive to the identification of benign and malignant category 3 or 4 small breast lesions. Material and Methods. We evaluated 30 malignant and 77 benign small breast lesions using CEUS. The range of enhancement, type of enhancement strength, intensity of enhancement, and enhancement patterns were independent factors included to assess the BI-RADS categories. Results. Of the nonenhanced breast lesions, 97.8% (44/45) were malignant, while, of the hyperplasic nodules, 96.8% (30/31) showed no enhancement in our study. Category changes of the lesions were made according to the features determined using CEUS. The results showed that these features could improve diagnostic sensitivity (from 70.0 to 80.0, 80.0, 90.0, and 90.0%), reduce the negative likelihood ratio (from 0.33 to 0.22, 0.25, 0.11, and 0.12), and improve the NPV (from 88.8 to 92.2, 91.2, 96.2, and 95.5%). However, this was not conducive to improve diagnostic specificity or the PPV. Conclusion. The vast majority of nonenhanced small breast lesions were malignant and most of the hyperplasic nodules showed no contrast enhancement. As a reference, CEUS was helpful in identifying BI-RADS category 3 or 4 small breast lesions. Jian-xing Zhang, Li-shan Cai, Ling Chen, Jiu-long Dai, and Guang-hui Song Copyright © 2014 Jian-xing Zhang et al. All rights reserved. Hypofractionated High-Dose Irradiation with Positron Emission Tomography Data for the Treatment of Glioblastoma Multiforme Thu, 22 May 2014 09:40:51 +0000 This research paper presents clinical outcomes of hypofractionated high-dose irradiation by intensity-modulated radiation therapy (Hypo-IMRT) with 11C-methionine positron emission tomography (MET-PET) data for the treatment of glioblastoma multiforme (GBM). A total of 45 patients with GBM were treated with Hypo-IMRT after surgery. Gross tumor volume (GTV) was defined as the area of enhanced lesion on MRI, including MET-PET avid region; clinical target volume (CTV) was the area with 5 mm margin surrounding the GTV; planning target volume (PTV) was the area with 15 mm margin surrounding the CTV, including MET-PET moderate region. Hypo-IMRT was performed in 8 fractions; planning the dose for GTV was escalated to 68 Gy and that for CTV was escalated to 56 Gy, while keeping the dose delivered to the PTV at 40 Gy. Concomitant and adjuvant TMZ chemotherapy was administered. At a median follow-up of 18.7 months, median overall survival (OS) was 20.0 months, and median progression-free survival was 13.0 months. The 1- and 2-year OS rates were 71.2% and 26.3%, respectively. Adjuvant TMZ chemotherapy was significantly predictive of OS on multivariate analysis. Late toxicity included 7 cases of Grade 3-4 radiation necrosis. Hypo-IMRT with MET-PET data appeared to result in favorable survival outcomes for patients with GBM. Kazuhiro Miwa, Masayuki Matsuo, Shin-ichi Ogawa, Jun Shinoda, Yoshitaka Asano, Takeshi Ito, Kazutoshi Yokoyama, Jitsuhiro Yamada, Hirohito Yano, and Toru Iwama Copyright © 2014 Kazuhiro Miwa et al. All rights reserved. The Effect of Superparamagnetic Iron Oxide with iRGD Peptide on the Labeling of Pancreatic Cancer Cells In Vitro: A Preliminary Study Mon, 19 May 2014 05:23:31 +0000 The iRGD peptide loaded with iron oxide nanoparticles for tumor targeting and tissue penetration was developed for targeted tumor therapy and ultrasensitive MR imaging. Binding of iRGD, a tumor homing peptide, is mediated by integrins, which are widely expressed on the surface of cells. Several types of small molecular drugs and nanoparticles can be transfected into cells with the help of iRGD peptide. Thus, we postulate that SPIO nanoparticles, which have good biocompatibility, can also be transfected into cells using iRGD. Despite the many kinds of cell labeling studies that have been performed with SPIO nanoparticles and RGD peptide or its analogues, only a few have applied SPIO nanoparticles with iRGD peptide in pancreatic cancer cells. This paper reports our preliminary findings regarding the effect of iRGD peptide (CRGDK/RGPD/EC) combined with SPIO on the labeling of pancreatic cancer cells. The results suggest that SPIO with iRGD peptide can enhance the positive labeling rate of cells and the uptake of SPIO. Optimal functionalization was achieved with the appropriate concentration or concentration range of SPIO and iRGD peptide. This study describes a simple and economical protocol to label panc-1 cells using SPIO in combination with iRGD peptide and may provide a useful method to improve the sensitivity of pancreatic cancer imaging. Hou Dong Zuo, Wei Wu Yao, Tian Wu Chen, Jiang Zhu, Juan Juan Zhang, Yu Pu, Gang Liu, and Xiao Ming Zhang Copyright © 2014 Hou Dong Zuo et al. All rights reserved. Biodistribution and SPECT Imaging Study of 99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma Mon, 19 May 2014 00:00:00 +0000 A peptide containing Asn-Gly-Arg(NGR) sequence was synthesized and directly labeled with . Its radiochemical characteristics, biodistribution, and SPECT imaging were evaluated in nude mice bearing human HepG2 hepatoma. Nude mice bearing HepG2 were randomly divided into 5 groups with 5 mice in each group and injected with ~7.4 MBq . The SPECT images were acquired in 1, 4, 8, and 12 h postinjection via caudal vein. The metabolism of tracers was determined in major organs at different time points, which demonstrated rapid, significant tumor uptake and slow tumor washout. The control group mice were blocked by coinjecting unlabelled NGR (20 mg/kg). Tumor uptake was () ID/g at 1 h, with the highest uptake of () ID/g at 8 h. In comparison, the uptake of the blocked control group was () ID/g at 1 h after injection. The SPECT static images and the tumor/muscle (T/NT) value were obtained. The highest T/NT value was at 8 h. The xenografted tumor became visible at 1 h and the clearest image of the tumor was observed at 8 h. In conclusion, can be efficiently prepared and it exhibited good properties for the potential SPECT imaging agent of tumor. Wenhui Ma, Zhe Wang, Weidong Yang, Xiaowei Ma, Fei Kang, and Jing Wang Copyright © 2014 Wenhui Ma et al. All rights reserved. Time Sensitivity Factor of Single Pulmonary Nodule: A New Cancer Characteristic Metabolic Parameter by -FDG PET Sun, 18 May 2014 10:48:37 +0000 Objective. To calculate the time sensitivity factor () for discriminating the solitary pulmonary nodule (SPN) by FDG PET at different time points. Methods. The multiple time-point FDG PET images from 41 patients for evaluating SPN seen on chest X-ray or CT were prospectively analyzed to calculate and evaluate against the gold standard of tissue histology () or long term clinicoradiographic follow-up (). The maximal standardized uptake values (SUV) at the 3 hourly time points were measured. The was calculated using at 3 different time intervals. ROC analysis of the parameters was performed to evaluate the optimal cut-off value and their accuracy in classifying the SPN. Results. The SUV in malignant SPN was higher than the corresponding value in benign lesions at all 3 hourly time points (). The parameters using 3 different time intervals all significantly separated the two groups () with an optimal cut-off point near the theoretical value of zero with a high sensitivity of 100% and specificity of 86%. Conclusion. The can be calculated for SPNs using multiple time-point FDG PET, providing a tumor characteristic metabolic parameter with high discrimination power using a simple positive value representing malignancy. Ching-Yuan Cheng, Kwo-Whei Lee, Chiang-Hsuan Lee, Yeu-Sheng Tyan, Cheng-Yi Cheng, Jhi-Joung Wang, Chao-Wei Yang, Wen-Sheng Huang, and Ching-Yee Oliver Wong Copyright © 2014 Ching-Yuan Cheng et al. All rights reserved. Diagnostic Performance of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in the Postchemotherapy Management of Patients with Seminoma: Systematic Review and Meta-Analysis Thu, 15 May 2014 11:10:31 +0000 Objective. To meta-analyze published data about the diagnostic performance of fluorine-18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the postchemotherapy management of patients with seminoma. Methods. A comprehensive literature search of studies published through January 2014 on this topic was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity and specificity, positive and negative predictive values (PPV and NPV), accuracy, and area under the summary ROC curve (AUC) of 18F-FDG-PET or PET/CT on a per examination-based analysis were calculated. Subgroup analyses considering the size of residual/recurrent lesions were carried out. Results. Nine studies including 375 scans were selected. The pooled analysis provided the following results: sensitivity 78% (95% confidence interval (95% CI): 67–87%), specificity 86% (95% CI: 81–89%), PPV 58% (95% CI: 48–68%), NPV 94% (95% CI: 90–96%), and accuracy 84% (95% CI: 80–88%). The AUC was 0.90. A better diagnostic accuracy of 18F-FDG-PET or PET/CT in evaluating residual/recurrent lesions >3 cm compared to those <3 cm was found. Conclusions. 18F-FDG-PET and PET/CT were demonstrated to be accurate imaging methods in the postchemotherapy management of patients with seminoma; nevertheless possible sources of false-negative and false-positive results should be considered. The literature focusing on this setting still remains limited and cost-effectiveness analyses are warranted. Giorgio Treglia, Ramin Sadeghi, Salvatore Annunziata, Carmelo Caldarella, Francesco Bertagna, and Luca Giovanella Copyright © 2014 Giorgio Treglia et al. All rights reserved. Preliminary Experience with Small Animal SPECT Imaging on Clinical Gamma Cameras Wed, 14 May 2014 12:41:13 +0000 The traditional lack of techniques suitable for in vivo imaging has induced a great interest in molecular imaging for preclinical research. Nevertheless, its use spreads slowly due to the difficulties in justifying the high cost of the current dedicated preclinical scanners. An alternative for lowering the costs is to repurpose old clinical gamma cameras to be used for preclinical imaging. In this paper we assess the performance of a portable device, that is, working coupled to a single-head clinical gamma camera, and we present our preliminary experience in several small animal applications. Our findings, based on phantom experiments and animal studies, provided an image quality, in terms of contrast-noise trade-off, comparable to dedicated preclinical pinhole-based scanners. We feel that our portable device offers an opportunity for recycling the widespread availability of clinical gamma cameras in nuclear medicine departments to be used in small animal SPECT imaging and we hope that it can contribute to spreading the use of preclinical imaging within institutions on tight budgets. P. Aguiar, J. Silva-Rodríguez, M. Herranz, and A. Ruibal Copyright © 2014 P. Aguiar et al. All rights reserved. Dysfunction of Affective Network in Post Ischemic Stroke Depression: A Resting-State Functional Magnetic Resonance Imaging Study Wed, 14 May 2014 08:30:27 +0000 Objective. Previous studies have demonstrated that stroke characteristics and social and psychological factors jointly contribute to the development of poststroke depression (PSD). The purpose of this study was to identify altered functional connectivity (FC) of the affective network (AN) in patients with PSD and to explore the correlation between FC and the severity of PSD. Materials and Methods. 26 PSD patients, 24 stroke patients without depression, and 24 age-matched normal controls underwent the resting-state functional MRI (fMRI) scanning. The bilateral anterior cingulated cortices (ACCs) were selected as regions of interest (ROIs). FC was calculated and compared among the three groups. The association between FC and Hamilton Depression Rate Scale (HDRS) scores of PSD group was investigated. Results. The FC of the AN was disrupted in PSD patients compared to stroke patients without depression and normal controls. Moreover, the left orbital part of inferior frontal gyrus which indicated altered FC was significantly correlated with HDRS scores in PSD patients. Conclusions. Dysfunction of the affective network may be one of the reasons of the development of PSD. Peiyao Zhang, Qin Xu, Jianping Dai, Jun Wang, Ning Zhang, and Yuejia Luo Copyright © 2014 Peiyao Zhang et al. All rights reserved. Diagnostic Accuracy of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in the Evaluation of the Primary Tumor in Patients with Cholangiocarcinoma: A Meta-Analysis Tue, 13 May 2014 08:01:42 +0000 Objective. To meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) or PET/computed tomography (PET/CT) for primary tumor evaluation in patients with cholangiocarcinoma (CCa). Methods. A comprehensive literature search of studies published through December 31, 2013, was performed. Pooled sensitivity and specificity were calculated on a per patient based analysis. Subgroup analyses considering the device used (PET versus PET/CT) and the localization of the primary tumor (intrahepatic cholangiocarcinoma (IH-CCa), extrahepatic cholangiocarcinoma (EH-CCa), and hilar cholangiocarcinoma (H-CCa)) were carried out. Results. Twenty-three studies including 1232 patients were included in the meta-analysis. Pooled sensitivity and specificity of 18F-FDG-PET or PET/CT were 81% and 82%, respectively. Pooled sensitivity and specificity, respectively, were 80% and 89% for PET, 82% and 75% for PET/CT, 95% and 83% for IH-CCa, 84% and 95% for H-CCa, and 76% and 74% for EH-CCa. Conclusions.  18F-FDG-PET and PET/CT were demonstrated to be accurate diagnostic imaging methods for primary tumor evaluation in patients with CCa. These tools have a better diagnostic accuracy in patients with IH-CCa than in patients with EH-CCa. Further studies are needed to evaluate the accuracy of 18F-FDG-PET or PET/CT in patients with H-CCa. Salvatore Annunziata, Carmelo Caldarella, Daniele Antonio Pizzuto, Federica Galiandro, Ramin Sadeghi, Luca Giovanella, and Giorgio Treglia Copyright © 2014 Salvatore Annunziata et al. All rights reserved. Time-Intensity Curve Parameters in Rectal Cancer Measured Using Endorectal Ultrasonography with Sterile Coupling Gels Filling the Rectum: Correlations with Tumor Angiogenesis and Clinicopathological Features Tue, 13 May 2014 00:00:00 +0000 The primary aim of this study was to investigate the relationship between contrast-enhanced ultrasonography (CEUS) imaging parameters and clinicopathological features of rectal carcinoma and assess their potential as new radiological prognostic predictors. A total of 66 rectal carcinoma patients were analyzed with the time-intensity curve of CEUS. The parameter arrival time (AT), time to peak enhancement (TTP), wash-in time (WIT), enhanced intensity (EI), and ascending slope (AS) were measured. Microvessel density (MVD) was evaluated by immunohistochemical staining of surgical specimens. All findings were analysed prospectively and correlated with tumor staging, histological grading, and MVD. The mean values of AT, TTP, WIT, EI, and AS value of the rectal carcinoma were  dB, and , respectively. A positive linear correlation was found between the EI and MVD in rectal carcinoma , and there was a significant difference for EI among histological grading . EI decreased as T stage increased with a trend of association noted . EI of contrast enhanced endorectal ultrasonography provides noninvasive biomarker of tumor angiogenesis in rectal cancer. CEUS data have the potential to predict patient prognosis. Yong Wang, Lin Li, Yi-Xiang J. Wang, Ning-Yi Cui, Shuang-Mei Zou, Chun-Wu Zhou, and Yu-Xin Jiang Copyright © 2014 Yong Wang et al. All rights reserved. New Progress in Angiogenesis Therapy of Cardiovascular Disease by Ultrasound Targeted Microbubble Destruction Mon, 12 May 2014 08:21:28 +0000 Angiogenesis plays a vital part in the pathogenesis and treatment of cardiovascular disease and has become one of the hotspots that are being discussed in the past decades. At present, the promising angiogenesis therapies are gene therapy and stem cell therapy. Besides, a series of studies have shown that the ultrasound targeted microbubble destruction (UTMD) was a novel gene delivery system, due to its advantages of noninvasiveness, low immunogenicity and toxicity, repeatability and temporal and spatial target specificity; UTMD has also been used for angiogenesis therapy of cardiovascular disease. In this review, we mainly discuss the combination of UTMD and gene therapy or stem cell therapy which is applied in angiogenesis therapy in recent researches, and outline the future challenges and good prospects of these approaches. Yang-Ying Liao, Zhi-Yi Chen, Yi-Xiang Wang, Yan Lin, Feng Yang, and Qiu-Lan Zhou Copyright © 2014 Yang-Ying Liao et al. All rights reserved. New SPECT and PET Radiopharmaceuticals for Imaging Cardiovascular Disease Sun, 11 May 2014 12:55:48 +0000 Nuclear cardiology has experienced exponential growth within the past four decades with converging capacity to diagnose and influence management of a variety of cardiovascular diseases. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m radiotracers or thallium-201 has dominated the field; however new hardware and software designs that optimize image quality with reduced radiation exposure are fuelling a resurgence of interest at the preclinical and clinical levels to expand beyond MPI. Other imaging modalities including positron emission tomography (PET) and magnetic resonance imaging (MRI) continue to emerge as powerful players with an expanded capacity to diagnose a variety of cardiac conditions. At the forefront of this resurgence is the development of novel target vectors based on an enhanced understanding of the underlying pathophysiological process in the subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered to target a specific subcellular process has the capacity to improve diagnostic accuracy and deliver enhanced prognostic information to alter management. This paper, while not comprehensive, will review the recent advancements in radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis, atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry and preclinical and clinical development in addition to molecular imaging with emerging modalities such as cardiac MRI and PET-MR will be discussed. Oyebola O. Sogbein, Matthieu Pelletier-Galarneau, Thomas H. Schindler, Lihui Wei, R. Glenn Wells, and Terrence D. Ruddy Copyright © 2014 Oyebola O. Sogbein et al. All rights reserved. 124Iodine: A Longer-Life Positron Emitter Isotope—New Opportunities in Molecular Imaging Thu, 08 May 2014 13:24:27 +0000 124Iodine (124I) with its 4.2 d half-life is particularly attractive for in vivo detection and quantification of longer-term biological and physiological processes; the long half-life of 124I is especially suited for prolonged time in vivo studies of high molecular weight compounds uptake. Numerous small molecules and larger compounds like proteins and antibodies have been successfully labeled with 124I. Advances in radionuclide production allow the effective availability of sufficient quantities of 124I on small biomedical cyclotrons for molecular imaging purposes. Radioiodination chemistry with 124I relies on well-established radioiodine labeling methods, which consists mainly in nucleophilic and electrophilic substitution reactions. The physical characteristics of 124I permit taking advantages of the higher PET image quality. The availability of new molecules that may be targeted with 124I represents one of the more interesting reasons for the attention in nuclear medicine. We aim to discuss all iodine radioisotopes application focusing on 124I, which seems to be the most promising for its half-life, radiation emissions, and stability, allowing several applications in oncological and nononcological fields. Giuseppe Lucio Cascini, Artor Niccoli Asabella, Antonio Notaristefano, Antonino Restuccia, Cristina Ferrari, Domenico Rubini, Corinna Altini, and Giuseppe Rubini Copyright © 2014 Giuseppe Lucio Cascini et al. All rights reserved. The Copper Radioisotopes: A Systematic Review with Special Interest to 64Cu Wed, 07 May 2014 10:14:35 +0000 Copper (Cu) is an important trace element in humans; it plays a role as a cofactor for numerous enzymes and other proteins crucial for respiration, iron transport, metabolism, cell growth, and hemostasis. Natural copper comprises two stable isotopes, 63Cu and 65Cu, and 5 principal radioisotopes for molecular imaging applications (60Cu, 61Cu, 62Cu, and 64Cu) and in vivo targeted radiation therapy (64Cu and 67Cu). The two potential ways to produce Cu radioisotopes concern the use of the cyclotron or the reactor. A noncopper target is used to produce noncarrier-added Cu thanks to a chemical separation from the target material using ion exchange chromatography achieving a high amount of radioactivity with the lowest possible amount of nonradioactive isotopes. In recent years, Cu isotopes have been linked to antibodies, proteins, peptides, and nanoparticles for preclinical and clinical research; pathological conditions that influence Cu metabolism such as Menkes syndrome, Wilson disease, inflammation, tumor growth, metastasis, angiogenesis, and drug resistance have been studied. We aim to discuss all Cu radioisotopes application focusing on 64Cu and in particular its form 64CuCl2 that seems to be the most promising for its half-life, radiation emissions, and stability with chelators, allowing several applications in oncological and nononcological fields. Artor Niccoli Asabella, Giuseppe Lucio Cascini, Corinna Altini, Domenico Paparella, Antonio Notaristefano, and Giuseppe Rubini Copyright © 2014 Artor Niccoli Asabella et al. All rights reserved. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats Tue, 06 May 2014 12:40:42 +0000 The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate) with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain () and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg) of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity. María Guadalupe Prado-Ochoa, Ricardo Alfonso Gutiérrez-Amezquita, Víctor Hugo Abrego-Reyes, Ana María Velázquez-Sánchez, Marco Antonio Muñoz-Guzmán, Patricia Ramírez-Noguera, Enrique Angeles, and Fernando Alba-Hurtado Copyright © 2014 María Guadalupe Prado-Ochoa et al. All rights reserved. Acoustic Radiation Force Impulse Elastography for Efficacy Evaluation after Hepatocellular Carcinoma Radiofrequency Ablation: A Comparative Study with Contrast-Enhanced Ultrasound Tue, 06 May 2014 12:39:07 +0000 Aim. To explore acoustic radiation force impulse (ARFI) elastography in assessing residual tumors of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). Materials and Methods. There were 83 HCC lesions among 72 patients. All patients were examined with ARFI, contrast enhanced ultrasound (CEUS), and CT or MRI. Tumor brightness on virtual touch tissue imaging (VTI) and shear wave velocity (SWV) were assessed before and approximately one month after RFA. Results. There were 14 residual tumors after RFA. VTI showed that all the tumors were darker after RFA. VTI was not able to distinguish the ablated lesions and the residual tumors. 13 residual tumor lesions were detected by CEUS. All completely ablated nodules had SWV demonstration of x.xx., while with those residual nodules, 6 tumors had x.xx measurement and 8 tumors had measurable SWV. nine lesions with residual tumors occurred in cirrhosis subjects and 5 lesions with residual tumors occurred in fibrosis subjects; there was no residual tumor in the normal liver subjects. Conclusion. VTI technique cannot demonstrate residual tumor post RFA. While SWV measurement of less than x.xx is likely associated with residual tumors, measurement of less than x.xx cannot exclude residual tumors. Liver cirrhosis is associated with decreased chance of a complete ablation. Xiaohong Xu, Liangping Luo, Jiexin Chen, Jiexin Wang, Honglian Zhou, Mingyi Li, Zhanqiang Jin, Nianping Chen, Huilai Miao, Manzhou Lin, Wei Dai, Anil T. Ahuja, and Yi-Xiang J. Wang Copyright © 2014 Xiaohong Xu et al. All rights reserved. Depressive Symptoms in Multiple Sclerosis from an In Vivo Study with TBSS Sun, 04 May 2014 11:07:26 +0000 Clinically significant depression can impact up to 50% of patients with multiple sclerosis (MS) over a course of their life time, which is associated with an increased morbidity and mortality. In our study, fifteen relapsing-remitting MS (RRMS) patients and 15 age- and gender-matched normal controls were included. Diffusion tensor imaging (DTI) was acquired by employing a single-shot echo planar imaging sequence on a 3.0 T MR scanner and fractional anisotropy (FA) was performed with tract-based spatial statistics (TBSS) approach. Finally, widespread WM and GM abnormalities were observed in RRMS patients. Moreover, the relationships between the depressive symptoms which can be measured by Hamilton depression rating scale (HAMD) as well as clinical disabilities measured by the expanded disability status scale (EDSS) and FA changes were listed. There was a positive relation between EDSS and the FA changes in the right inferior parietal lobule, while negative relation was located in the left anterior cingulate cortex and hippocampus. Also a positive relation between HAMD and FA changes was found in the right posterior middle cingulate gyrus, the right hippocampus, the left hypothalamus, the right precentral gyrus, and the posterior cingulate which demonstrated a link between the depressive symptoms and clinically relevant brain areas in RRMS patients. Yujuan Shen, Lijun Bai, Ying Gao, Fangyuan Cui, Zhongjian Tan, Yin Tao, Chuanzhu Sun, and Li Zhou Copyright © 2014 Yujuan Shen et al. All rights reserved. Prospective Analysis of 18F-FDG PET/CT Predictive Value in Patients with Low Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy and Conservative Surgery Sun, 04 May 2014 07:00:29 +0000 This study prospectively assessed 18F-FDG PET/CT in predicting the response of locally advanced low rectal cancer (LRC) to neoadjuvant chemoradiation (nCRT). Methods. 56 patients treated with chemoradiation underwent two 18F-FDG PET/CT scans (baseline and 5-6 weeks post-nCRT). 18F-FDG uptake (SUVmax and SUVmean) and differences between baseline (SUV1) and post-nCRT (SUV2) scans (ΔSUV and RI%) were evaluated. Results were related to the Mandard’s TRG and (y)pTNM. Results. 18F-FDG PET/CT sensitivity, specificity, accuracy, PPV and NPV resulted in 88.6%, 66.7%, 83.92%, 90.7%, and 61.5%. SUV2 resulted in better than SUV1 to predict nCRT response by TRG, with no significant statistical difference between the SUVmax2 and SUVmean2 AUC (0.737 versus 0.736; ). The same applies to the (y)pTNM (0.798 versus 0.782; ). In relation to the TRG, RI values had a higher AUC than ΔSUV, with no significant difference between RImax and RImean (0.672 versus 0.695; ). The same applied to the (y)pTNM (0.742 versus 0.741; ). In both cases ΔSUV does not appear to be a good predictive tool. Logistic regression confirmed the better predictive role of SUVmax2 for the (y)pTNM (odds ratio = 1.58) and SUVmean2 for the TRG (odds ratio = 1.87). Conclusions. 18F-FDG PET/CT can evaluate response to nCRT in LRC, even if more studies are required to define the most significant parameter for predicting pathologic tumor changes. Artor Niccoli-Asabella, Corinna Altini, Raffaele De Luca, Margherita Fanelli, Domenico Rubini, Cosimo Caliandro, Severino Montemurro, and Giuseppe Rubini Copyright © 2014 Artor Niccoli-Asabella et al. All rights reserved. Value of Fused 18F-Choline-PET/MRI to Evaluate Prostate Cancer Relapse in Patients Showing Biochemical Recurrence after EBRT: Preliminary Results Wed, 30 Apr 2014 08:09:56 +0000 Purpose. We compared the accuracy of 18F-Choline-PET/MRI with that of multiparametric MRI (mMRI), 18F-Choline-PET/CT, 18F-Fluoride-PET/CT, and contrast-enhanced CT (CeCT) in detecting relapse in patients with suspected relapse of prostate cancer (PC) after external beam radiotherapy (EBRT). We assessed the association between standard uptake value (SUV) and apparent diffusion coefficient (ADC). Methods. We evaluated 21 patients with biochemical relapse after EBRT. Patients underwent 18F-Choline-PET/contrast-enhanced (Ce)CT, 18F-Fluoride-PET/CT, and mMRI. Imaging coregistration of PET and mMRI was performed. Results. 18F-Choline-PET/MRI was positive in 18/21 patients, with a detection rate (DR) of 86%. DRs of 18F-Choline-PET/CT, CeCT, and mMRI were 76%, 43%, and 81%, respectively. In terms of DR the only significant difference was between 18F-Choline-PET/MRI and CeCT. On lesion-based analysis, the accuracy of 18F-Choline-PET/MRI, 18F-Choline-PET/CT, CeCT, and mMRI was 99%, 95%, 70%, and 85%, respectively. Accuracy, sensitivity, and NPV of 18F-Choline-PET/MRI were significantly higher than those of both mMRI and CeCT. On whole-body assessment of bone metastases, the sensitivity of 18F-Choline-PET/CT and 18F-Fluoride-PET/CT was significantly higher than that of CeCT. Regarding local and lymph node relapse, we found a significant inverse correlation between ADC and SUV-max. Conclusion. 18F-Choline-PET/MRI is a promising technique in detecting PC relapse. Arnoldo Piccardo, Francesco Paparo, Riccardo Picazzo, Mehrdad Naseri, Paolo Ricci, Andrea Marziano, Lorenzo Bacigalupo, Ennio Biscaldi, Gian Andrea Rollandi, Filippo Grillo-Ruggieri, and Mohsen Farsad Copyright © 2014 Arnoldo Piccardo et al. All rights reserved. Biological Evaluation of 131I- and CF750-Labeled Dmab(scFv)-Fc Antibodies for Xenograft Imaging of CD25-Positive Tumors Sun, 27 Apr 2014 00:00:00 +0000 A Dmab(scFv)-Fc antibody containing the single chain variable fragment of a humanized daclizumab antibody and the Fc fragment of a human IgG1 antibody was produced via recombinant expression in Pichia pastoris. The Dmab(scFv)-Fc antibody forms a dimer in solution, and it specifically binds CD25-positive tumor cells and tumor tissues. For tumor imaging, the Dmab(scFv)-Fc antibody was labeled with the 131I isotope and CF750 fluorescent dye, respectively. After intravenous injection of mice bearing CD25-positive tumor xenografts, tumor uptake of the 131I-Dmab(scFv)-Fc antibody was visible at 1 h, and clear images were obtained at 5 h using SPECT/CT. After systemic administration of the CF750-Dmab(scFv)-Fc antibody, tumor uptake was present as early as 1 h, and tumor xenografts could be kinetically imaged within 9 h after injection. These results indicate that the Dmab(scFv)-Fc antibody rapidly and specifically targets CD25-positive tumor cells, suggesting the potential of this antibody as an imaging agent for the diagnosis of lymphomatous-type ATLL. Qing Fan, Huawei Cai, Hao Yang, Lin Li, Cen Yuan, Xiaofeng Lu, and Lin Wan Copyright © 2014 Qing Fan et al. All rights reserved. Role of 99mTc-ECD SPECT in the Management of Children with Craniosynostosis Wed, 16 Apr 2014 16:45:59 +0000 Purpose of the Report. There is a paucity of data on correlation of various imaging modalities with clinical findings in craniosynostosis. Moreover, no study has specifically reported the role of -ECD SPECT in a large number of subjects with craniosynostosis. Materials and Methods. We prospectively analyzed a cohort of 85 patients with craniosynostosis from year 2007 to 2012. All patients underwent evaluation with -ECD SPECT and the results were correlated with radiological and surgical findings. Results. -ECD SPECT revealed regional perfusion abnormalities in the cerebral hemisphere corresponding to the fused sutures preoperatively that disappeared postoperatively in all the cases. Corresponding to this, the mean mental performance quotient (MPQ) increased significantly postoperatively only in those children with absent perfusion defect postoperatively. Conclusions. Our study suggests that early surgery and release of craniosynostosis in patients with preoperative perfusion defects (absent on -ECD SPECT study) are beneficial, as theylead to improved MPQ after surgery. Mayadhar Barik, Minu Bajpai, Rashmi Ranajn Das, Arun Malhotra, Shasanka Shekhar Panda, Manas Kumar Sahoo, and Sadanand Dwivedi Copyright © 2014 Mayadhar Barik et al. All rights reserved. Bimodal Imaging Probes for Combined PET and OI: Recent Developments and Future Directions for Hybrid Agent Development Wed, 16 Apr 2014 12:13:32 +0000 Molecular imaging—and especially positron emission tomography (PET)—has gained increasing importance for diagnosis of various diseases and thus experiences an increasing dissemination. Therefore, there is also a growing demand for highly affine PET tracers specifically accumulating and visualizing target structures in the human body. Beyond the development of agents suitable for PET alone, recent tendencies aim at the synthesis of bimodal imaging probes applicable in PET as well as optical imaging (OI), as this combination of modalities can provide clinical advantages. PET, due to the high tissue penetration of the -radiation emitted by PET nuclides, allows a quantitative imaging able to identify and visualize tumors and metastases in the whole body. OI on the contrary visualizes photons exhibiting only a limited tissue penetration but enables the identification of tumor margins and infected lymph nodes during surgery without bearing a radiation burden for the surgeon. Thus, there is an emerging interest in bimodal agents for PET and OI in order to exploit the potential of both imaging techniques for the imaging and treatment of tumor diseases. This short review summarizes the available hybrid probes developed for dual PET and OI and discusses future directions for hybrid agent development. Uwe Seibold, Björn Wängler, Ralf Schirrmacher, and Carmen Wängler Copyright © 2014 Uwe Seibold et al. All rights reserved. Selective Changes of Resting-State Brain Oscillations in aMCI: An fMRI Study Using ALFF Mon, 14 Apr 2014 00:00:00 +0000 Mild cognitive impairment (MCI) refers to a transitional state between normal aging and dementia and is a syndrome with cognitive decline greater than expected for an individual’s age and educational level. As a subtype of MCI, amnestic mild cognitive impairment (aMCI) most often leads to Alzheimer’s disease. This study aims to elucidate the altered brain activation in patients with aMCI using resting-state functional magnetic resonance. We observed Frequency-dependent changes in the amplitude of low-frequency fluctuations in aMCI patients (), and normal subjects (). At the same time, we took gray matter volume as a covariate. We found that aMCI patients had decreased amplitude of low-frequency fluctuation signal in left superior temporal gyrus, right middle temporal gyrus, right inferior parietal lobe, and right postcentral gyrus compared to the control group. Specially, aMCI patients showed increased signal in left superior and middle frontal gyrus. Our results suggested that increased activation in frontal lobe of aMCI patients may indicate effective recruitment of compensatory brain resources. This finding and interpretation may lead to the better understanding of cognitive changes of aMCI. Zhilian Zhao, Jie Lu, Xiuqin Jia, Wang Chao, Ying Han, Jianping Jia, and Kuncheng Li Copyright © 2014 Zhilian Zhao et al. All rights reserved. Role of PET and SPECT in the Study of Amyotrophic Lateral Sclerosis Thu, 10 Apr 2014 08:28:18 +0000 Amyotrophic lateral sclerosis has been defined as a “heterogeneous group of neurodegenerative syndromes characterized by progressive muscle paralysis caused by the degeneration of motor neurons allocated in primary motor cortex, brainstem, and spinal cord.” A comprehensive diagnostic workup for ALS usually includes several electrodiagnostic, clinical laboratory and genetic tests. Neuroimaging exams, such as computed tomography, magnetic resonance imaging and spinal cord myelogram, may also be required. Nuclear medicine, with PET and SPECT, may also play a role in the evaluation of patients with ALS, and provide additional information to the clinicians. This paper aims to offer to the reader a comprehensive review of the different radiotracers for the assessment of the metabolism of glucose (FDG), the measurement of cerebral blood flow (CBF), or the evaluation of neurotransmitters, astrocytes, and microglia by means of newer and not yet clinically diffuse radiopharmaceuticals. Angelina Cistaro, Vincenzo Cuccurullo, Natale Quartuccio, Marco Pagani, Maria Consuelo Valentini, and Luigi Mansi Copyright © 2014 Angelina Cistaro et al. All rights reserved. Early Monitoring Antiangiogenesis Treatment Response of Sunitinib in U87MG Tumor Xenograft by 18F-FLT MicroPET/CT Imaging Wed, 09 Apr 2014 14:10:30 +0000 Aim. It was aimed to monitor early treatment response of Sunitinib in U87MG models mimicking glioblastoma multiforme by longitudinal 18F-FLT microPET/CT imaging in this study. Methods. U87MG tumor mice were intragastrically injected with Sunitinib at a dose of 80 mg/kg for consecutive 7 days. 18F-FLT microPET/CT scans were acquired on days 0, 1, 3, 7, and 13 after therapy. Tumor sizes and body weight were measured. Tumor samples were collected for immunohistochemical analysis of proliferation and microvessel density (MVD) with anti-Ki67 and anti-CD31, respectively. Results. The uptake ratios of tumor to the contralateral muscle (T/M) of 18F-FLT in the Sunitinib group decreased from baseline to day 3 (T/M0 = 2.98 ± 0.33; T/M3 = 2.23 ± 0.36; ), reached the bottom on day 7 (T/M7 = 1.96 ± 0.35; ), and then recovered on day 13. The T/M of 18F-FLT uptake in the control group remained around 3.0. There was no difference for the tumor size between both groups until day 11. 18F-FLT uptakes of tumor were correlated with Ki67 staining index and MVD. Conclusion. Early therapy response to Sunitinib could be predicted via 18F-FLT PET, which will contribute to monitoring antiangiogenesis treatment. Xiao Bao, Ming-Wei Wang, Yong-Ping Zhang, and Ying-Jian Zhang Copyright © 2014 Xiao Bao et al. All rights reserved. Erratum to “Estimation of the Lateral Ventricles Volumes from a 2D Image and Its Relationship with Cerebrospinal Fluid Flow” Wed, 02 Apr 2014 06:12:52 +0000 Bader Chaarani, Cyrille Capel, Jadwiga Zmudka, Joel Daouk, Anthony Fichten, Catherine Gondry-Jouet, Roger Bouzerar, and Olivier Balédent Copyright © 2014 Bader Chaarani et al. All rights reserved. SPECT- and PET-Based Approaches for Noninvasive Diagnosis of Acute Renal Allograft Rejection Tue, 01 Apr 2014 12:48:06 +0000 Molecular imaging techniques such as single photon emission computed tomography (SPECT) or positron emission tomography are promising tools for noninvasive diagnosis of acute allograft rejection (AR). Given the importance of renal transplantation and the limitation of available donors, detailed analysis of factors that affect transplant survival is important. Episodes of acute allograft rejection are a negative prognostic factor for long-term graft survival. Invasive core needle biopsies are still the “goldstandard” in rejection diagnostics. Nevertheless, they are cumbersome to the patient and carry the risk of significant graft injury. Notably, they cannot be performed on patients taking anticoagulant drugs. Therefore, a noninvasive tool assessing the whole organ for specific and fast detection of acute allograft rejection is desirable. We herein review SPECT- and PET-based approaches for noninvasive molecular imaging-based diagnostics of acute transplant rejection. Helga Pawelski, Uta Schnöckel, Dominik Kentrup, Alexander Grabner, Michael Schäfers, and Stefan Reuter Copyright © 2014 Helga Pawelski et al. All rights reserved. Hypothalamus-Anchored Resting Brain Network Changes before and after Sertraline Treatment in Major Depression Thu, 20 Mar 2014 00:00:00 +0000 Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline) on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect. Rui Yang, Hongbo Zhang, Xiaoping Wu, Junle Yang, Mingyue Ma, Yanjun Gao, Hongsheng Liu, and Shengbin Li Copyright © 2014 Rui Yang et al. All rights reserved. A Survey of FDG- and Amyloid-PET Imaging in Dementia and GRADE Analysis Wed, 19 Mar 2014 13:47:54 +0000 PET based tools can improve the early diagnosis of Alzheimer’s disease (AD) and differential diagnosis of dementia. The importance of identifying individuals at risk of developing dementia among people with subjective cognitive complaints or mild cognitive impairment has clinical, social, and therapeutic implications. Within the two major classes of AD biomarkers currently identified, that is, markers of pathology and neurodegeneration, amyloid- and FDG-PET imaging represent decisive tools for their measurement. As a consequence, the PET tools have been recognized to be of crucial value in the recent guidelines for the early diagnosis of AD and other dementia conditions. The references based recommendations, however, include large PET imaging literature based on visual methods that greatly reduces sensitivity and specificity and lacks a clear cut-off between normal and pathological findings. PET imaging can be assessed using parametric or voxel-wise analyses by comparing the subject’s scan with a normative data set, significantly increasing the diagnostic accuracy. This paper is a survey of the relevant literature on FDG and amyloid-PET imaging aimed at providing the value of quantification for the early and differential diagnosis of AD. This allowed a meta-analysis and GRADE analysis revealing high values for PET imaging that might be useful in considering recommendations. Perani Daniela, Schillaci Orazio, Padovani Alessandro, Nobili Flavio Mariano, Iaccarino Leonardo, Della Rosa Pasquale Anthony, Frisoni Giovanni, and Caltagirone Carlo Copyright © 2014 Perani Daniela et al. All rights reserved. Current and Future Lymphatic Imaging Modalities for Tumor Staging Sun, 16 Mar 2014 11:14:01 +0000 Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review. Ghulam Murtaza, Kuo Gao, Tiegang Liu, Imran Tariq, Ashif Sajjad, Muhammad Rouf Akram, Meiying Niu, Guokai Liu, Zahid Mehmood, and Guihua Tian Copyright © 2014 Ghulam Murtaza et al. All rights reserved. Functional MRI Study of Working Memory Impairment in Patients with Symptomatic Carotid Artery Disease Thu, 20 Feb 2014 11:32:09 +0000 The neuropsychological tests in patients with internal carotid artery (ICA) demonstrated cognitive deficits associated with frontal lobe dysfunction, but the pathophysiological mechanism of memory impairment is not fully understood. This study evaluated relationship between degree of ICA stenosis and frontal activations induced by working memory (WM) task using fMRI. The fMRI data of 21 patients with unilateral ICA stenosis (left/right, 11/10) and 21 controls were analyzed. In comparison with controls, ICA patients demonstrated significant activations in middle frontal gyrus (MFG) bilaterally, particularly in left MFG. In right ICA stenosis, there was slightly less MFG activation than that of controls. Importantly, lower MFG activity was associated with higher stenosis of ipsilateral ICA. For left ICA stenosis, weaker activation in left MFG was negatively correlated with degree of stenosis. Similarly, for right ICA stenosis, there was a significant negative correlation between right ICA stenosis and weaker activation of right MFG. Cognitive impairments in ICA stenosis were associated with frontal lobe dysfunctions. Left ICA stenosis had worse WM impairments than right ICA stenosis, which was affected by the degree of stenosis. Shasha Zheng, Miao Zhang, Xiaoyi Wang, Qingfeng Ma, Hua Shu, Jie Lu, and Kuncheng Li Copyright © 2014 Shasha Zheng et al. All rights reserved. Loss of Microstructural Integrity in the Limbic-Subcortical Networks for Acute Symptomatic Traumatic Brain Injury Thu, 20 Feb 2014 08:47:29 +0000 Previous studies reported discrepant white matter diffusivity in mild traumatic brain injury (mTBI) on the base of Glasgow Coma Scale, which are unreliable for some TBI severity indicators and the frequency of missing documentation in the medical record. In the present study, we adopted the Mayo classification system for TBI severity. In this system, the mTBI is also divided into two groups as “probable and symptomatic” TBI. We aimed to investigate altered microstructural integrity in symptomatic acute TBI (<1 week) by using tract-based spatial statics (TBSS) approach. A total of 12 patients and 13 healthy volunteers were involved and underwent MRI scans including conventional scan, and SWI and DTI. All the patients had no visible lesions by using conventional and SWI neuroimaging techniques, while showing widespread declines in the fractional anisotropy (FA) of gray matter and white matter throughout the TBSS skeleton, particularly in the limbic-subcortical structures. By contrast, symptomatic TBI patients showed no significant enhanced changes in FA compared to the healthy controls. A better understanding of the acute changes occurring following symptomatic TBI may increase our understanding of neuroplasticity and continuing degenerative change, which, in turn, may facilitate advances in management and intervention. Yanan Zhu, Zhengjun Li, Lijun Bai, Yin Tao, Chuanzhu Sun, Min Li, Longmei Zheng, Bao Zhu, Jun Yao, Heping Zhou, and Ming Zhang Copyright © 2014 Yanan Zhu et al. All rights reserved. Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury Wed, 19 Feb 2014 12:43:30 +0000 Spinal cord injury (SCI) is a serious disease of the center nervous system (CNS). It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET), magnetic resonance imaging (MRI), optical imaging (i.e., bioluminescence imaging (BLI)) gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI. Fahuan Song, Mei Tian, and Hong Zhang Copyright © 2014 Fahuan Song et al. All rights reserved. New Researches and Application Progress of Commonly Used Optical Molecular Imaging Technology Mon, 17 Feb 2014 11:45:37 +0000 Optical molecular imaging, a new medical imaging technique, is developed based on genomics, proteomics and modern optical imaging technique, characterized by non-invasiveness, non-radiativity, high cost-effectiveness, high resolution, high sensitivity and simple operation in comparison with conventional imaging modalities. Currently, it has become one of the most widely used molecular imaging techniques and has been applied in gene expression regulation and activity detection, biological development and cytological detection, drug research and development, pathogenesis research, pharmaceutical effect evaluation and therapeutic effect evaluation, and so forth, This paper will review the latest researches and application progresses of commonly used optical molecular imaging techniques such as bioluminescence imaging and fluorescence molecular imaging. Zhi-Yi Chen, Yi-Xiang Wang, Feng Yang, Yan Lin, Qiu-Lan Zhou, and Yang-Ying Liao Copyright © 2014 Zhi-Yi Chen et al. All rights reserved. Advance of Molecular Imaging Technology and Targeted Imaging Agent in Imaging and Therapy Thu, 13 Feb 2014 12:42:12 +0000 Molecular imaging is an emerging field that integrates advanced imaging technology with cellular and molecular biology. It can realize noninvasive and real time visualization, measurement of physiological or pathological process in the living organism at the cellular and molecular level, providing an effective method of information acquiring for diagnosis, therapy, and drug development and evaluating treatment of efficacy. Molecular imaging requires high resolution and high sensitive instruments and specific imaging agents that link the imaging signal with molecular event. Recently, the application of new emerging chemical technology and nanotechnology has stimulated the development of imaging agents. Nanoparticles modified with small molecule, peptide, antibody, and aptamer have been extensively applied for preclinical studies. Therapeutic drug or gene is incorporated into nanoparticles to construct multifunctional imaging agents which allow for theranostic applications. In this review, we will discuss the characteristics of molecular imaging, the novel imaging agent including targeted imaging agent and multifunctional imaging agent, as well as cite some examples of their application in molecular imaging and therapy. Zhi-Yi Chen, Yi-Xiang Wang, Yan Lin, Jin-Shan Zhang, Feng Yang, Qiu-Lan Zhou, and Yang-Ying Liao Copyright © 2014 Zhi-Yi Chen et al. All rights reserved. Automated Identification of Dementia Using FDG-PET Imaging Sun, 02 Feb 2014 14:17:00 +0000 Parametric FDG-PET images offer the potential for automated identification of the different dementia syndromes. However, various existing image features and classifiers have their limitations in characterizing and differentiating the patterns of this disease. We reported a hybrid feature extraction, selection, and classification approach, namely, the GA-MKL algorithm, for separating patients with suspected Alzheimer’s disease and frontotemporal dementia from normal controls. In this approach, we extracted three groups of features to describe the average level, spatial variation, and asymmetry of glucose metabolic rates in 116 cortical volumes. An optimal combination of features, that is, capable of classifying dementia cases was identified by a genetic algorithm- (GA-) based method. The condition of each FDG-PET study was predicted by applying the selected features to a multikernel learning (MKL) machine, in which the weighting parameter of each kernel function can be automatically estimated. We compared our approach to two state-of-the-art dementia identification algorithms on a set of 129 clinical cases and improved the performance in separating the dementia types, achieving accuracy of 94.62%. There is a very good agreement between the proposed automated technique and the diagnosis made by clinicians. Yong Xia, Shen Lu, Lingfeng Wen, Stefan Eberl, Michael Fulham, and David Dagan Feng Copyright © 2014 Yong Xia et al. All rights reserved. F-18 Labeled Vasoactive Intestinal Peptide Analogue in the PET Imaging of Colon Carcinoma in Nude Mice Thu, 26 Dec 2013 10:52:55 +0000 As large amount of vasoactive intestinal peptide (VIP) receptors are expressed in various tumors and VIP-related diseases, radiolabeled VIP provides a potential PET imaging agent for VIP receptor. However, structural modification of VIP is required before being radiolabeled and used for VIP receptor imaging due to its poor in vivo stability. As a VIP analogue, [R8, 15, 21, L17]-VIP exhibited improved stability and receptor specificity in preliminary studies. In this study, F-18 labeled [, L17]-VIP was produced with the radiochemical yield being as high as (decay-for-corrected, ) achieved within 100 min, a specific activity of 255 GBq/μmol, and a radiochemical purity as high as 99% as characterized by radioactive HPLC, TLC, and SDS-Page radioautography. A biodistribution study in normal mice also demonstrated fast elimination of F-18 labeled [, L17]-VIP in the blood, liver, and gastrointestinal tracts. A further micro-PET imaging study in C26 colon carcinoma bearing mice confirmed the high tumor specificity, with the tumor/muscle radioactivity uptake ratio being as high as 3.03 at 60 min following injection, and no apparent radioactivity concentration in the intestinal tracts. In addition, blocking experiment and Western Blot test further confirmed its potential in PET imaging of VIP receptor-positive tumor. Dengfeng Cheng, Yuxia Liu, Hua Shen, Lifang Pang, Duanzhi Yin, Yongxian Wang, Shanqun Li, and Hongcheng Shi Copyright © 2013 Dengfeng Cheng et al. All rights reserved. Acoustic Droplet Vaporization in Biology and Medicine Wed, 20 Nov 2013 08:29:30 +0000 This paper reviews the literature regarding the use of acoustic droplet vaporization (ADV) in clinical applications of imaging, embolic therapy, and therapeutic delivery. ADV is a physical process in which the pressure waves of ultrasound induce a phase transition that causes superheated liquid nanodroplets to form gas bubbles. The bubbles provide ultrasonic imaging contrast and other functions. ADV of perfluoropentane was used extensively in imaging for preclinical trials in the 1990s, but its use declined rapidly with the advent of other imaging agents. In the last decade, ADV was proposed and explored for embolic occlusion therapy, drug delivery, aberration correction, and high intensity focused ultrasound (HIFU) sensitization. Vessel occlusion via ADV has been explored in rodents and dogs and may be approaching clinical use. ADV for drug delivery is still in preclinical stages with initial applications to treat tumors in mice. Other techniques are still in preclinical studies but have potential for clinical use in specialty applications. Overall, ADV has a bright future in clinical application because the small size of nanodroplets greatly reduces the rate of clearance compared to larger contrast agent bubbles and yet provides the advantages of ultrasonographic contrast, acoustic cavitation, and nontoxicity of conventional perfluorocarbon contrast agent bubbles. Chung-Yin Lin and William G. Pitt Copyright © 2013 Chung-Yin Lin and William G. Pitt. All rights reserved. Microfluidics for Synthesis of Peptide-Based PET Tracers Thu, 31 Oct 2013 15:08:49 +0000 Positron emission tomography (PET) is a powerful noninvasive tool for acquisition of the physiological parameters in human and animals with the help of PET tracers. Among all the PET tracers, radiolabeled peptides have been widely explored for cancer-related receptor imaging due to their high affinity and specificity to receptors. But radiochemistry procedures for production of peptide-based PET tracers are usually complex, which makes large-scale clinical studies relatively challenging. New radiolabeling technologies which could simplify synthesis and purification procedures, are extremely needed. Over the last decade, microfluidics and lab-on-a-chip (LOC) technology have boomed as powerful tools in the field of organic chemistry, which potentially provide significant help to the PET chemistry. In this minireview, microfluidic radiolabeling technology is described and its application for synthesis of peptide-based PET tracers is summarized and discussed. Yang Liu, Mei Tian, and Hong Zhang Copyright © 2013 Yang Liu et al. All rights reserved. NSOM/QD-Based Visualization of GM1 Serving as Platforms for TCR/CD3 Mediated T-Cell Activation Wed, 30 Oct 2013 15:35:19 +0000 Direct molecular imaging of nanoscale relationship between T-cell receptor complexes (TCR/CD3) and gangliosidosis GM1 before and after T-cell activation has not been reported. In this study, we made use of our expertise of near-field scanning optical microscopy(NSOM)/immune-labeling quantum dots- (QD-)based dual-color imaging system to visualize nanoscale profiles for distribution and organization of TCR/CD3, GM1, as well as their nanospatial relationship and their correlation with PKCθ signaling cascade during T-cell activation. Interestingly, after anti-CD3/anti-CD28 Ab co-stimulation, both TCR/CD3 and GM1 were clustered to form nanodomains; moreover, all of TCR/CD3 nanodomains were colocalized with GM1 nanodomains, indicating that the formation of GM1 nanodomains was greatly correlated with TCR/CD3 mediated signaling. Specially, while T-cells were pretreated with PKCθ signaling inhibitor rottlerin to suppress IL-2 cytokine production, no visible TCR/CD3 nanodomains appeared while a lot of GM1 nanodomains were still observed. However, while T-cells are pretreated with PKCαβ signaling inhibitor GÖ6976 to suppress calcium-dependent manner, all of TCR/CD3 nanodomains were still colocalized with GM1 nanodomains. These findings possibly support the notion that the formation of GM1 nanodomains indeed serves as platforms for the recruitment of TCR/CD3 nanodomains, and TCR/CD3 nanodomains are required for PKCθ signaling cascades and T-cell activation Liyun Zhong, Zhun Zhang, Xiaoxu Lu, Shengde Liu, Crystal Y. Chen, and Zheng W. Chen Copyright © 2013 Liyun Zhong et al. All rights reserved. Abacus Training Modulates the Neural Correlates of Exact and Approximate Calculations in Chinese Children: An fMRI Study Wed, 30 Oct 2013 09:10:27 +0000 Exact (EX) and approximate (AP) calculations rely on distinct neural circuits. However, the training effect on the neural correlates of EX and AP calculations is largely unknown, especially for the AP calculation. Abacus-based mental calculation (AMC) is a particular arithmetic skill that can be acquired by long-term abacus training. The present study investigated whether and how the abacus training modulates the neural correlates of EX and AP calculations by functional magnetic resonance imaging (fMRI). Neural activations were measured in 20 abacus-trained and 19 nontrained Chinese children during AP and EX calculation tasks. Our results demonstrated that: (1) in nontrained children, similar neural regions were activated in both tasks, while the size of activated regions was larger in AP than those in the EX; (2) in abacus-trained children, no significant difference was found between these two tasks; (3) more visuospatial areas were activated in abacus-trained children under the EX task compared to the nontrained. These results suggested that more visuospatial strategies were used by the nontrained children in the AP task compared to the EX; abacus-trained children adopted a similar strategy in both tasks; after long-term abacus training, children were more inclined to apply a visuospatial strategy during processing EX calculations. Fenglei Du, Feiyan Chen, Yongxin Li, Yuzheng Hu, Mei Tian, and Hong Zhang Copyright © 2013 Fenglei Du et al. All rights reserved. Molecular Imaging-Guided Theranostics and Personalized Medicine Thu, 24 Oct 2013 19:17:02 +0000 David J. Yang, Fong Y. Tsai, Tomio Inoue, Mei-Hsiu Liao, Fan-Lin Kong, and Shaoli Song Copyright © 2013 David J. Yang et al. All rights reserved. Multimodality Molecular Imaging of Stem Cells Therapy for Stroke Tue, 08 Oct 2013 17:22:44 +0000 Stem cells have been proposed as a promising therapy for treating stroke. While several studies have demonstrated the therapeutic benefits of stem cells, the exact mechanism remains elusive. Molecular imaging provides the possibility of the visual representation of biological processes at the cellular and molecular level. In order to facilitate research efforts to understand the stem cells therapeutic mechanisms, we need to further develop means of monitoring these cells noninvasively, longitudinally and repeatedly. Because of tissue depth and the blood-brain barrier (BBB), in vivo imaging of stem cells therapy for stroke has unique challenges. In this review, we describe existing methods of tracking transplanted stem cells in vivo, including magnetic resonance imaging (MRI), nuclear medicine imaging, and optical imaging (OI). Each of the imaging techniques has advantages and drawbacks. Finally, we describe multimodality imaging strategies as a more comprehensive and potential method to monitor transplanted stem cells for stroke. Fangfang Chao, Yehua Shen, Hong Zhang, and Mei Tian Copyright © 2013 Fangfang Chao et al. All rights reserved. Changes of Regulatory T and B Cells in Patients with Papillary Thyroid Carcinoma after 131I Radioablation: A Preliminary Study Tue, 08 Oct 2013 11:23:42 +0000 Introduction. Lymphocytic infiltration and specific lymphocytes subsets may play important roles in papillary thyroid carcinoma (PTC) progression and prognosis. In this study, we try to understand the influence of 131I radioablation on the important lymphocytes subtypes of regulatory T and B cells (Tregs and Bregs). Methods. Peripheral blood mononuclear cells from 30 PTC patients before and after 131I therapy, and 20 healthy donors were collected. The expression of Tregs (CD4+CD25+) and B cell (CD5+CD19+) and production and secretion of interleukin 10 (IL-10) were analyzed by FACS and ELISA assay, respectively. Results. For Tregs percentage in peripheral blood lymphocytes, there was no difference between pretreatment and control and between posttreatment and control. Compared with pretherapy, increased Tregs infiltration was noted in posttherapy (). Although no difference was between pretreatment and control, compared with these two groups, decreased CD19+ and CD5+CD19+ B cell percentage in posttreatment was observed (). Among these groups, no significant difference was displayed in intracellular IL-10 production and extracellular IL-10 secretion. Conclusions. 131I Radioablation increased Tregs and decreased CD19+ and CD5+CD19+ B cells percentage after treatment. However, it has no effect on IL-10 and lymphocytes in peripheral blood. Therefore, longer follow-up of Tregs and Bregs should be further investigated. Lei Jiang, Yanxia Zhan, Yusen Gu, Yi Ye, Yunfeng Cheng, and Hongcheng Shi Copyright © 2013 Lei Jiang et al. All rights reserved. Molecular Imaging in Traditional Chinese Medicine Therapy for Neurological Diseases Mon, 07 Oct 2013 17:32:58 +0000 With the speeding tendency of aging society, human neurological disorders have posed an ever increasing threat to public health care. Human neurological diseases include ischemic brain injury, Alzheimer’s disease, Parkinson’s disease, and spinal cord injury, which are induced by impairment or specific degeneration of different types of neurons in central nervous system. Currently, there are no more effective treatments against these diseases. Traditional Chinese medicine (TCM) is focused on, which can provide new strategies for the therapy in neurological disorders. TCM, including Chinese herb medicine, acupuncture, and other nonmedication therapies, has its unique therapies in treating neurological diseases. In order to improve the treatment of these disorders by optimizing strategies using TCM and evaluate the therapeutic effects, we have summarized molecular imaging, a new promising technology, to assess noninvasively disease specific in cellular and molecular levels of living models in vivo, that was applied in TCM therapy for neurological diseases. In this review, we mainly focus on applying diverse molecular imaging methodologies in different TCM therapies and monitoring neurological disease, and unveiling the mysteries of TCM. Zefeng Wang, Haitong Wan, Jinhui Li, Hong Zhang, and Mei Tian Copyright © 2013 Zefeng Wang et al. All rights reserved. A Partial Volume Effect Correction Tailored for 18F-FDG-PET Oncological Studies Thu, 19 Sep 2013 18:20:26 +0000 We have developed, optimized, and validated a method for partial volume effect (PVE) correction of oncological lesions in positron emission tomography (PET) clinical studies, based on recovery coefficients (RC) and on PET measurements of lesion-to-background ratio () and of lesion metabolic volume. An operator-independent technique, based on an optimised threshold of the maximum lesion uptake, allows to define an isocontour around the lesion on PET images in order to measure both lesion radioactivity uptake and lesion metabolic volume. RC are experimentally derived from PET measurements of hot spheres in hot background, miming oncological lesions. RC were obtained as a function of PET measured sphere-to-background ratio and PET measured sphere metabolic volume, both resulting from the threshold-isocontour technique. PVE correction of lesions of a diameter ranging from 10 mm to 40 mm and for measured from 2 to 30 was performed using measured RC curves tailored at answering the need to quantify a large variety of real oncological lesions by means of PET. Validation of the PVE correction method resulted to be accurate (>89%) in clinical realistic conditions for lesion diameter > 1 cm, recovering >76% of radioactivity for lesion diameter < 1 cm. Results from patient studies showed that the proposed PVE correction method is suitable and feasible and has an impact on a clinical environment. F. Gallivanone, C. Canevari, L. Gianolli, C. Salvatore, P. A. Della Rosa, M. C. Gilardi, and I. Castiglioni Copyright © 2013 F. Gallivanone et al. All rights reserved. Pre- and Postsynaptic Dopamine SPECT in Idiopathic Parkinsonian Diseases: A Follow-Up Study Thu, 19 Sep 2013 10:29:02 +0000 We prospectively evaluated the diagnostic contribution of 123I-FP-Cit (DAT) and 123I-IBZM (IBZM) SPECT in 29 patients with Parkinson's disease (PD) ( years) and 28 patients with atypical parkinsonian diseases (APD) ( years). Twelve had multiple system atrophy (MSA) and 16 progressive supranuclear palsy (PSP). Sixteen age-matched healthy controls (HC) were included. DAT and IBZM SPECTs were made at baseline and after 1 year in all PD patients and in 20 (DAT) and 18 (IBZM) of the APD patients, and after 3 years in 22 (DAT) and 17 (IBZM) of the PD patients and in 10 (DAT) and 10 (IBZM) of the APD patients. The relative DAT uptake decrease was faster in PD and PSP than in HC and MSA. In PSP the DAT uptake was lower than in MSA after 1 year but not after 3 years. Baseline IBZM uptake was not significantly different between patients and HC or between PD and APD. One year after initiated dopaminergic treatment the mean IBZM uptake in the MSA patients remained high compared to PSP and after 3 years compared to PD, PSP, and HC. Thus, the pattern of uptake of these ligands over time may be of value in discriminating between these diagnoses. Susanna Jakobson Mo, Jan Linder, Lars Forsgren, Henrik Holmberg, Anne Larsson, and Katrine Riklund Copyright © 2013 Susanna Jakobson Mo et al. All rights reserved. Somatostatin Receptor-Based Molecular Imaging and Therapy for Neuroendocrine Tumors Wed, 11 Sep 2013 08:36:04 +0000 Neuroendocrine tumors (NETs) are tumors originated from neuroendocrine cells in the body. The localization and the detection of the extent of NETs are important for diagnosis and treatment, which should be individualized according to the tumor type, burden, and symptoms. Molecular imaging of NETs with high sensitivity and specificity is achieved by nuclear medicine method using single photon-emitting and positron-emitting radiopharmaceuticals. Somatostatin receptor imaging (SRI) using SPECT or PET as a whole-body imaging technique has become a crucial part of the management of NETs. The radiotherapy with somatostatin analogues labeled with therapeutic beta emitters, such as lutetium-177 or yttrium-90, has been proved to be an option of therapy for patients with unresectable and metastasized NETs. Molecular imaging can deliver an important message to improve the outcome for patients with NETs by earlier diagnosis, better choice of the therapeutic method, and evaluation of the therapeutic response. Ling Wang, Kun Tang, Qi Zhang, Huanbin Li, Zhengwei Wen, Hongzheng Zhang, and Hong Zhang Copyright © 2013 Ling Wang et al. All rights reserved. Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173 Sun, 08 Sep 2013 15:54:23 +0000 Purpose. The radioligand [11C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R). The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR). Procedures. Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney. To achieve IR, acute ischemia was created with a balloon inserted into the left renal artery and inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the balloon. Blood chemistries, urine specific gravity and PH values, and circulating hormones of the renin angiotensin system were measured and PET imaging was performed one week after IR. Cortical time-activity curves obtained from a 90 min [11C]KR31173 dynamic PET study were processed with a compartmental model that included two tissue compartments connected in parallel. Radioligand binding quantified by radioligand retention (80 min value to maximum value ratio) was compared to the binding parameters derived from the compartmental model. A binding ratio was calculated as , where and represented the distribution volumes of specific binding and nonspecific binding. Receptor binding was also determined by autoradiography in vitro. Results. Correlations between rate constants and binding parameters derived by the convolution and deconvolution curve fittings were significant . Also significant was the correlation between the retention parameter derived from the tissue activity curve () and the retention parameter derived from the impulse response function (). Furthermore, significant correlations were found between these two retention parameters and DVR. Measurements with PET showed no significant changes in the radioligand binding parameters caused by IR, and these in vivo findings were confirmed by autoradiography performed in vitro. Conclusions. Correlations between various binding parameters support the concept of the parallel connectivity compartmental model. If an arterial input function cannot be obtained, simple radioligand retention may be adequate for estimation of in vivo radioligand binding. Nedim C. M. Gulaldi, Jinsong Xia, Tao Feng, Kelvin Hong, William B. Mathews, Dawn Ruben, Ihab R. Kamel, Benjamin M. W. Tsui, and Zsolt Szabo Copyright © 2013 Nedim C. M. Gulaldi et al. All rights reserved. Effects of Anesthesia and Species on the Uptake or Binding of Radioligands In Vivo in the Göttingen Minipig Sun, 08 Sep 2013 12:05:00 +0000 Progress in neuroscience research often involves animals, as no adequate alternatives exist to animal models of living systems. However, both the physiological characteristics of the species used and the effects of anesthesia raise questions of common concern. Here, we demonstrate the confounding influences of these effects on tracer binding in positron emission tomography (PET). We determined the effects of two routinely used anesthetics (isoflurane and propofol) on the binding of two tracers of monoamine function, []SCH23390, a tracer of the dopamine D1 and D5 receptors, and the alpha2-adrenoceptor antagonist, []yohimbine, in Göttingen minipigs. The kinetics of SCH23390 in the pigs differed from those of our earlier studies in primates. With two different graphical analyses of uptake of SCH23390, the initial clearance values of this tracer were higher with isoflurane than with propofol anesthesia, indicative of differences in blood flow, whereas no significant differences were observed for the volumes of distribution of yohimbine. The study underscores the importance of differences of anesthesia and species when the properties of radioligands are evaluated under different circumstances that may affect blood flow and tracer uptake. These differences must be considered in the choice of a particular animal species and mode of anesthesia for a particular application. Aage K. O. Alstrup, Anne M. Landau, James E. Holden, Steen Jakobsen, Anna C. Schacht, Helene Audrain, Gregers Wegener, Axel K. Hansen, Albert Gjedde, and Doris J. Doudet Copyright © 2013 Aage K. O. Alstrup et al. All rights reserved. In Vivo Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study Sat, 31 Aug 2013 15:21:34 +0000 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin commonly used to produce an animal model of Parkinson’s disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO) synthase- (nNOS-) derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess in vivo due to its extremely short biological half-life, and so in vivo evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, in vivo localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI), intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF) in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first in vivo evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. Although the observed CBF change may be independent of the toxicogenesis of MPTP, this transient hyperperfusion state may serve as an early indicator of neuroinflammation. Tiing Yee Siow, Chiao-Chi V. Chen, Nina Wan, Kai-Ping N. Chow, and Chen Chang Copyright © 2013 Tiing Yee Siow et al. All rights reserved. A Comparison between 18F-FDG PET/CT Imaging and Biological and Radiological Findings in Restaging of Hepatoblastoma Patients Mon, 26 Aug 2013 09:36:30 +0000 Background. In this study we retrospectively evaluated if 18F-FDG-PET/CT provided incremental diagnostic information over CI in a group of hepatoblastoma patients performing restaging. Procedure. Nine patients (mean age: 5.9 years; range: 3.1–12 years) surgically treated for hepatoblastoma were followed up by clinical examination, serum -FP monitoring, and US. CI (CT or MRI) and PET/CT were performed in case of suspicion of relapse. Fine-needle aspiration biopsies (FNAB) were carried out for final confirmation if the results of CI, PET/CT, and/or -FP levels were suggestive of relapse. PET/CT and CI findings were analyzed for comparison purposes, using FNAB as reference standard. Results. -FP level was suggestive of disease recurrence in 8/9 patients. Biopsy was performed in 8/9 cases. CI and PET/CT resulted to be concordant in 5/9 patients (CI identified recurrence of disease, but 18F-FDG-PET/CT provided a better definition of disease extent); in 4/9 cases, CI diagnostic information resulted in negative findings, whereas PET/CT correctly detected recurrence of disease. 18F-FDG-PET/CT showed an agreement of 100% (8/8) with FNAB results. Conclusions. 18F-FDG-PET/CT scan seems to better assess HB patients with respect to CI and may provide incremental diagnostic value in the restaging of this group of patients. Angelina Cistaro, Giorgio Treglia, Manuela Pagano, Piercarlo Fania, Valentina Bova, Maria Eleonora Basso, Franca Fagioli, Umberto Ficola, and Natale Quartuccio Copyright © 2013 Angelina Cistaro et al. All rights reserved. Magnetic Resonance Imaging of Cardiovascular Fibrosis and Inflammation: From Clinical Practice to Animal Studies and Back Thu, 22 Aug 2013 10:06:20 +0000 Late gadolinium enhancement is the technique of choice for detecting myocardial fibrosis. Although this technique is used in a wide range of cardiovascular pathologies, ischemic cardiomyopathy and the workup for myocarditis and other cardiomyopathies make up a significant proportion of the total indications. Multiple studies during the last decade have demonstrated its utility to adequately characterize myocardial tissue and offer diagnostic and prognostic information. Recent T1 mapping techniques aim to overcome the limitations of late gadolinium enhancement to assess diffuse fibrosis. 19F magnetic resonance has recently emerged as a promising technique for the assessment of inflammation. In the following review we will discuss the basic aspects of fibrosis assessment with MR and its utility for diagnostic and prognostic evaluation. We will also address the topic of cardiovascular inflammation imaging with 19F as a potential new development that may broaden the indications for MR in the future. Adelina Doltra, Philipp Stawowy, Thore Dietrich, Christopher Schneeweis, Eckart Fleck, and Sebastian Kelle Copyright © 2013 Adelina Doltra et al. All rights reserved. The Predictive Value of Interim and Final [18F] Fluorodeoxyglucose Positron Emission Tomography after Rituximab-Chemotherapy in the Treatment of Non-Hodgkin's Lymphoma: A Meta-Analysis Wed, 14 Aug 2013 10:49:15 +0000 Background and Purpose. The aim of this study is to determine the prognostic value of interim and final FDG-PET in major histotypes of B-cell NHL patients treated with rituximab containing-chemotherapy. Methods. We searched for articles published in English, limited to lymphoma, rituximab, and FDG-PET, and dedicated to deal with the impact on progression and survival. The log hazard ratios (HR) and their variances were estimated. Results. A PubMed and Scopus review of published trials identified 13 studies of Progression-free survival (PFS) and overall survival (OS) which were set as the main outcome measures. The combined HRs of I-PET for PFS and OS in DLBCL were 4.4 () and 3.99 (), respectively. The combined HRs of F-PET for PFS and OS in DLBCL were 5.91 () and 6.75 (), respectively. Regarding to non-DLBCL with F-PET, the combined HRs of F-PET for PFS and OS were 4.05 () and 5.1 (), respectively. No publication bias existed. Conclusion. In DLBCL, both I-PET and F-PET can be performed for survival and progression analysis. But in other B-cell subtypes such as follicular lymphoma (FL) and mantle cell lymphoma (MCL), it would be necessary to perform F-PET for predictive purposes. Yuyuan Zhu, Jianda Lu, Xin Wei, Shaoli Song, and Gang Huang Copyright © 2013 Yuyuan Zhu et al. All rights reserved. Effect of Low Refocusing Angle in T1-Weighted Spin Echo and Fast Spin Echo MRI on Low-Contrast Detectability: A Comparative Phantom Study at 1.5 and 3 Tesla Tue, 06 Aug 2013 13:01:29 +0000 MRI tissue contrast is not well preserved at high field. In this work, we used a phantom with known, intrinsic contrast (3.6%) for model tissue pairs to test the effects of low angle refocusing pulses and magnetization transfer from adjacent slices on intrinsic contrast at 1.5 and 3 Tesla. Only T1-weighted spin echo sequences were tested since for such sequences the contrast loss, tissue heating, and image quality degradation at high fields seem to present significant diagnostic and quality issues. We hypothesized that the sources of contrast loss could be attributed to low refocusing angles that do not fulfill the Hahn spin echo conditions or to magnetization transfer effects from adjacent slices in multislice imaging. At 1.5 T the measured contrast was 3.6% for 180° refocusing pulses and 2% for 120° pulses, while at 3 T, it was 4% for 180° and only 1% for 120° refocusing pulses. There was no significant difference between single slice and multislice imaging suggesting little or no role played by magnetization transfer in the phantom chosen. Hence, one may conclude that low angle refocusing pulses not fulfilling the Hahn spin echo conditions are primarily responsible for significant deterioration of T1-weighted spin echo image contrast in high-field MRI. Subhendra N. Sarkar, Jason L. Mangosing, and Pooja R. Sarkar Copyright © 2013 Subhendra N. Sarkar et al. All rights reserved. Nonrigid Image Registration in Digital Subtraction Angiography Using Multilevel B-Spline Mon, 22 Jul 2013 08:04:49 +0000 We address the problem of motion artifact reduction in digital subtraction angiography (DSA) using image registration techniques. Most of registration algorithms proposed for application in DSA, have been designed for peripheral and cerebral angiography images in which we mainly deal with global rigid motions. These algorithms did not yield good results when applied to coronary angiography images because of complex nonrigid motions that exist in this type of angiography images. Multiresolution and iterative algorithms are proposed to cope with this problem, but these algorithms are associated with high computational cost which makes them not acceptable for real-time clinical applications. In this paper we propose a nonrigid image registration algorithm for coronary angiography images that is significantly faster than multiresolution and iterative blocking methods and outperforms competing algorithms evaluated on the same data sets. This algorithm is based on a sparse set of matched feature point pairs and the elastic registration is performed by means of multilevel B-spline image warping. Experimental results with several clinical data sets demonstrate the effectiveness of our approach. Mansour Nejati, Saeid Sadri, and Rassoul Amirfattahi Copyright © 2013 Mansour Nejati et al. All rights reserved. Molecular Imaging of Nonsmall Cell Lung Carcinomas Expressing Active Mutant EGFR Kinase Using PET with [124I]-Morpholino-IPQA Wed, 17 Jul 2013 09:13:32 +0000 Mutations in the kinase domain of epidermal growth factor receptor (EGFR) have high levels of basal receptor phosphorylation and are associated with clinical responsiveness to Iressa in patients with nonsmall cell lung cancer (NSCLC). This study aimed to assess the feasibility of morpholino-[124I]IPQA derivative as an in vivo PET imaging tool for the expression of different EGFR mutants in NSCLC. In vitro radiotracer accumulation and washout studies demonstrated a rapid accumulation and progressive retention after washout of morpholino-[131I]IPQA derivative in high EGFR-expressing H1299 NSCLC derivative cell lines (L858R and E746-A750 del cell lines), but not in EGFR-transfected H1299 cell line and vector-transfected H1299 cell line. Using the morpholino-[124I]IPQA derivative, we obtained noninvasive microPET images of EGFR activity in L858R and E746-A750 del subcutaneous tumor xenografts, but not in subcutaneous tumor xenografts grown form control cell line. Different EGFR mutant (activity) tumors have a different morpholino-[∗I]IPQA derivative uptake. However, it still needs to modify the structure of IPQA to increase its water solubility and reduce hepatobiliary clearance. Morpholino-[124I]IPQA derivative may be a potential probe for selection of the candidate patients suffering from NSCLC for the small molecule tyrosine kinase inhibitor therapy (e.g., Iressa) in the future. Skye Hsin-Hsien Yeh, Chien-Feng Lin, Fan-Lin Kong, Hsin-Ell Wang, Ya-Ju Hsieh, Juri G. Gelovani, and Ren-Shyan Liu Copyright © 2013 Skye Hsin-Hsien Yeh et al. All rights reserved. Synthesis and Biological Evaluation of O-[3-18F-fluoropropyl]-α-methyl Tyrosine in Mesothelioma-Bearing Rodents Tue, 09 Jul 2013 09:34:45 +0000 Radiolabeled tyrosine analogs enter cancer cells via upregulated amino acid transporter system and have been shown to be superior to 18F-fluoro-2-deoxy-D-glucose (18F-FDG) in differential diagnosis in cancers. In this study, we synthesized O-[3-19F-fluoropropyl]-α-methyl tyrosine (19F-FPAMT) and used manual and automated methods to synthesize O-[3-18F-fluoropropyl]-α-methyl tyrosine (18F-FPAMT) in three steps: nucleophilic substitution, deprotection of butoxycarbonyl, and deesterification. Manual and automated synthesis methods produced 18F-FPAMT with a radiochemical purity >96%. The decay-corrected yield of 18F-FPAMT by manual synthesis was 34% at end-of-synthesis (88 min). The decay-corrected yield of 18F-FPAMT by automated synthesis was 15% at end-of-synthesis (110 min). 18F-FDG and 18F-FPAMT were used for in vitro and in vivo studies to evaluate the feasibility of 18F-FPAMT for imaging rat mesothelioma (IL-45). In vitro studies comparing 18F-FPAMT with 18F-FDG revealed that 18F-FDG had higher uptake than that of 18F-FPAMT, and the uptake ratio of 18F-FPAMT reached the plateau after being incubated for 60 min. Biodistribution studies revealed that the accumulation of 18F-FPAMT in the heart, lungs, thyroid, spleen, and brain was significantly lower than that of 18F-FDG. There was poor bone uptake in 18F-FPAMT for up to 3 hrs suggesting its in vivo stability. The imaging studies showed good visualization of tumors with 18F-FPAMT. Together, these results suggest that 18F-FPAMT can be successfully synthesized and has great potential in mesothelioma imaging. I-Hong Shih, Fan-Lin Kong, Mohammad S. Ali, Yinhan Zhang, Dong-Fang Yu, Xudong Duan, and David J. Yang Copyright © 2013 I-Hong Shih et al. All rights reserved. Affinity Labeling of Membrane Receptors Using Tissue-Penetrating Radiations Thu, 27 Jun 2013 14:05:59 +0000 Photoaffinity labeling, a useful in vivo biochemical tool, is limited when applied in vivo because of the poor tissue penetration by ultraviolet (UV) photons. This study investigates affinity labeling using tissue-penetrating radiation to overcome the tissue attenuation and irreversibly label membrane receptor proteins. Using X-ray (115 kVp) at low doses (<50 cGy or Rad), specific and irreversible binding was found on striatal dopamine transporters with 3 photoaffinity ligands for dopamine transporters, to different extents. Upon X-ray exposure (115 kVp), RTI-38 and RTI-78 ligands showed irreversible and specific binding to the dopamine transporter similar to those seen with UV exposure under other conditions. Similarly, gamma rays at higher energy (662 keV) also affect irreversible binding of photoreactive ligands to peripheral benzodiazepine receptors (by PK14105) and to the dopamine (D2) membrane receptors (by azidoclebopride), respectively. This study reports that X-ray and gamma rays induced affinity labeling of membrane receptors in a manner similar to UV with photoreactive ligands of the dopamine transporter, D2 dopamine receptor (D2R), and peripheral benzodiazepine receptor (PBDZR). It may provide specific noninvasive irreversible block or stimulation of a receptor using tissue-penetrating radiation targeting selected anatomic sites. Franklin C. Wong, John Boja, Beng Ho, Michael J. Kuhar, and Dean F. Wong Copyright © 2013 Franklin C. Wong et al. All rights reserved. Kidney Dosimetry in 177Lu and 90Y Peptide Receptor Radionuclide Therapy: Influence of Image Timing, Time-Activity Integration Method, and Risk Factors Thu, 20 Jun 2013 18:03:39 +0000 Kidney dosimetry in 177Lu and 90Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with 177Lu DOTATATE and 30 with 177Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for 177Lu therapy and 70 h for 90Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (-test, ), with DOTATATE affecting an increase of 25% compared to DOTATOC (-test, ). F. Guerriero, M. E. Ferrari, F. Botta, F. Fioroni, E. Grassi, A. Versari, A. Sarnelli, M. Pacilio, E. Amato, L. Strigari, L. Bodei, G. Paganelli, M. Iori, G. Pedroli, and M. Cremonesi Copyright © 2013 F. Guerriero et al. All rights reserved. The Adjunctive Digital Breast Tomosynthesis in Diagnosis of Breast Cancer Mon, 17 Jun 2013 15:50:08 +0000 Purpose. To compare the diagnostic performance of digital breast tomosynthesis (DBT) and digital mammography (DM) for breast cancers. Materials and Methods. Fifty-seven female patients with pathologically proved breast cancer were enrolled. Three readers gave a subjective assessment superiority of the index lesions (mass, focal asymmetry, architectural distortion, or calcifications) and a forced BIRADS score, based on DM reading alone and with additional DBT information. The relevance between BIRADS category and index lesions of breast cancer was compared by chi-square test. Result. A total of 59 breast cancers were reviewed, including 17 (28.8%) mass lesions, 12 (20.3%) focal asymmetry/density, 6 (10.2%) architecture distortion, 23 (39.0%) calcifications, and 1 (1.7%) intracystic tumor. Combo DBT was perceived to be more informative in 58.8% mass lesions, 83.3% density, 94.4% architecture distortion, and only 11.6% calcifications. As to the forced BIRADS score, 84.4% BIRADS 0 on DM was upgraded to BIRADS 4 or 5 on DBT, whereas only 27.3% BIRADS 4A on DM was upgraded on DBT, as BIRADS 4A lesions were mostly calcifications. A significant value (<0.001) between the BIRADS category and index lesions was noted. Conclusion. Adjunctive DBT gives exquisite information for mass lesion, focal asymmetry, and/or architecture distortion to improve the diagnostic performance in mammography. Tsung-Lung Yang, Huei-Lung Liang, Chen-Pin Chou, Jer-Shyung Huang, and Huay-Ben Pan Copyright © 2013 Tsung-Lung Yang et al. All rights reserved. Comparison of 99mTc-N-DBODC5 and 99mTc-MIBI of Myocardial Perfusion Imaging for Diagnosis of Coronary Artery Disease Tue, 11 Jun 2013 11:28:48 +0000 Despite recent advances in therapeutic and diagnostic approaches, coronary artery disease (CAD) and its related cardiac disorders represent the most common cause of death in the United States. Nuclear myocardial perfusion imaging (MPI) technologies play a pivotal role in the diagnosis and treatment design for CAD. Recently, in order to develop improved MPI agents for diagnosis of CAD, 99mTc-[bis(dimethoxypropylphosphinoethyl)-ethoxyethyl-amine(PNP5)]-[bis(N-ethoxyethyl)dithiocarbamato(DBODC)]nitride(N-DBODC5)(99mTc-N-DBODC5) with a faster liver clearance than conventional single-photon emission computed tomography (SPECT) imaging agents (technetium 99m sestamibi (99mTc-MIBI) or technetium 99m tetrofosmin) has been introduced. In preclinical and phase I studies, 99mTc-N-DBODC5 has shown characteristics of an essentially ideal MPI tracer. Importantly, however, there is no data to support the use of 99mTc-N-DBODC5 to evaluate myocardial ischemia in patients with suspected CAD. The present study was designed to assess the clinical value of this agent; the findings of stress and rest MPI after the administration of this agent were compared to those of stress and rest 99mTc-MIBI, as well as those of coronary angiography, with respect to the detection of CAD. Our findings indicated the usefulness of 99mTc-N-DBODC5 as a promising MPI agent. Haiyan Ma, Sijin Li, Zhifang Wu, Jianzhong Liu, Haiyan Liu, and Xiaoshan Guo Copyright © 2013 Haiyan Ma et al. All rights reserved. Managing Lymphoma with Non-FDG Radiotracers: Current Clinical and Preclinical Applications Thu, 06 Jun 2013 14:25:56 +0000 Nuclear medicine imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have played a prominent role in lymphoma management. PET with [18F]Fluoro-2-deoxy-D-glucose (FDG) is the most commonly used tool for lymphoma imaging. However, FDG-PET has several limitations that give the false positive or false negative diagnosis of lymphoma. Therefore, development of new radiotracers with higher sensitivity, specificity, and different uptake mechanism is in great demand in the management of lymphoma. This paper reviews non-FDG radiopharmaceuticals that have been applied for PET and SPECT imaging in patients with different types of lymphoma, with attention to diagnosis, staging, therapy response assessment, and surveillance for disease relapse. In addition, we introduce three radiolabeled anti-CD20 antibodies for radioimmunotherapy, which is another important arm for lymphoma treatment and management. Finally, the relatively promising radiotracers that are currently under preclinical development are also discussed in this paper. Fan-Lin Kong, Richard J. Ford, and David J. Yang Copyright © 2013 Fan-Lin Kong et al. All rights reserved. Clinical Application of Magnetic Resonance Imaging in Management of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy Wed, 05 Jun 2013 14:57:12 +0000 Neoadjuvant chemotherapy (NAC), also termed primary, induction, or preoperative chemotherapy, is traditionally used to downstage inoperable breast cancer. In recent years it has been increasingly used for patients who have operable cancers in order to facilitate breast-conserving surgery, achieve better cosmetic outcome, and improve prognosis by reaching pathologic complete response (pCR). Many studies have demonstrated that magnetic resonance imaging (MRI) can assess residual tumor size after NAC, and that provides critical information for planning of the optimal surgery. NAC also allows for timely adjustment of administered drugs based on response, so ineffective regimens could be terminated early to spare patients from unnecessary toxicity while allowing other effective regimens to work sooner. This review article summarizes the clinical application of MRI during NAC. The use of different MR imaging methods, including dynamic contrast-enhanced MRI, proton MR spectroscopy, and diffusion-weighted MRI, to monitor and evaluate the NAC response, as well as how changes of parameters measured at an early time after initiation of a drug regimen can predict final treatment outcome, are reviewed. MRI has been proven a valuable tool and will continue to provide important information facilitating individualized image-guided treatment and personalized management for breast cancer patients undergoing NAC. Jeon-Hor Chen and Min-Ying Su Copyright © 2013 Jeon-Hor Chen and Min-Ying Su. All rights reserved. Advanced MR Imaging of Gliomas: An Update Tue, 04 Jun 2013 08:37:21 +0000 Recent advances in the treatment of cerebral gliomas have increased the demands on noninvasive neuroimaging for the diagnosis, therapeutic planning, tumor monitoring, and patient outcome prediction. In the meantime, improved magnetic resonance (MR) imaging techniques have shown much potentials in evaluating the key pathological features of the gliomas, including cellularity, invasiveness, mitotic activity, angiogenesis, and necrosis, hence, further shedding light on glioma grading before treatment. In this paper, an update of advanced MR imaging techniques is reviewed, and their potential roles as biomarkers of tumor grading are discussed. Hung-Wen Kao, Shih-Wei Chiang, Hsiao-Wen Chung, Fong Y. Tsai, and Cheng-Yu Chen Copyright © 2013 Hung-Wen Kao et al. All rights reserved. The Potential Roles of 18F-FDG-PET in Management of Acute Stroke Patients Wed, 15 May 2013 15:26:33 +0000 Extensive efforts have recently been devoted to developing noninvasive imaging tools capable of delineating brain tissue viability (penumbra) during acute ischemic stroke. These efforts could have profound clinical implications for identifying patients who may benefit from tPA beyond the currently approved therapeutic time window and/or patients undergoing neuroendovascular treatments. To date, the DWI/PWI MRI and perfusion CT have received the most attention for identifying ischemic penumbra. However, their routine use in clinical settings remains limited. Preclinical and clinical PET studies with [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) have consistently revealed a decreased 18F-FDG uptake in regions of presumed ischemic core. More importantly, an elevated 18F-FDG uptake in the peri-ischemic regions has been reported, potentially reflecting viable tissues. To this end, this paper provides a comprehensive review of the literature on the utilization of 14C-2-DG and 18F-FDG-PET in experimental as well as human stroke studies. Possible cellular mechanisms and physiological underpinnings attributed to the reported temporal and spatial uptake patterns of 18F-FDG are addressed. Given the wide availability of 18F-FDG in routine clinical settings, 18F-FDG PET may serve as an alternative, non-invasive tool to MRI and CT for the management of acute stroke patients. Adomas Bunevicius, Hong Yuan, and Weili Lin Copyright © 2013 Adomas Bunevicius et al. All rights reserved. Toward the Era of a One-Stop Imaging Service Using an Angiography Suite for Neurovascular Disorders Tue, 14 May 2013 10:12:04 +0000 Transportation of patients requiring multiple diagnostic and imaging-guided therapeutic modalities is unavoidable in current radiological practice. This clinical scenario causes time delays and increased risk in the management of stroke and other neurovascular emergencies. Since the emergence of flat-detector technology in imaging practice in recent decades, studies have proven that flat-detector X-ray angiography in conjunction with contrast medium injection and specialized reconstruction algorithms can provide not only high-quality and high-resolution CT-like images but also functional information. This improvement in imaging technology allows quantitative assessment of intracranial hemodynamics and, subsequently in the same imaging session, provides treatment guidance for patients with neurovascular disorders by using only a flat-detector angiographic suite—a so-called one-stop quantitative imaging service (OSIS). In this paper, we review the recent developments in the field of flat-detector imaging and share our experience of applying this technology in neurovascular disorders such as acute ischemic stroke, cerebral aneurysm, and stenoocclusive carotid diseases. Sheng-Che Hung, Chung-Jung Lin, Wan-Yuo Guo, Feng-Chi Chang, Chao-Bao Luo, Michael Mu-Huo Teng, and Cheng-Yen Chang Copyright © 2013 Sheng-Che Hung et al. All rights reserved. Molecular Imaging of Hepatocellular Carcinoma Xenografts with Epidermal Growth Factor Receptor Targeted Affibody Probes Sun, 21 Apr 2013 10:19:27 +0000 Hepatocellular carcinoma (HCC) is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR) has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET) or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo. Ping Zhao, Xiaoyang Yang, Shibo Qi, Hongguang Liu, Han Jiang, Susan Hoppmann, Qizhen Cao, Mei-Sze Chua, Samuel K. So, and Zhen Cheng Copyright © 2013 Ping Zhao et al. All rights reserved. Pharmacodynamic Analysis of Magnetic Resonance Imaging-Monitored Focused Ultrasound-Induced Blood-Brain Barrier Opening for Drug Delivery to Brain Tumors Sun, 31 Mar 2013 10:57:15 +0000 Microbubble-enhanced focused ultrasound (FUS) can enhance the delivery of therapeutic agents into the brain for brain tumor treatment. The purpose of this study was to investigate the influence of brain tumor conditions on the distribution and dynamics of small molecule leakage into targeted regions of the brain after FUS-BBB opening. A total of 34 animals were used, and the process was monitored by 7T-MRI. Evans blue (EB) dye as well as Gd-DTPA served as small molecule substitutes for evaluation of drug behavior. EB was quantified spectrophotometrically. Spin-spin (R1) relaxometry and area under curve (AUC) were measured by MRI to quantify Gd-DTPA. We found that FUS-BBB opening provided a more significant increase in permeability with small tumors. In contrast, accumulation was much higher in large tumors, independent of FUS. The AUC values of Gd-DTPA were well correlated with EB delivery, suggesting that Gd-DTPA was a good indicator of total small-molecule accumulation in the target region. The peripheral regions of large tumors exhibited similar dynamics of small-molecule leakage after FUS-BBB opening as small tumors, suggesting that FUS-BBB opening may have the most significant permeability-enhancing effect on tumor peripheral. This study provides useful information toward designing an optimized FUS-BBB opening strategy to deliver small-molecule therapeutic agents into brain tumors. Po-Chun Chu, Wen-Yen Chai, Han-Yi Hsieh, Jiun-Jie Wang, Shiaw-Pyng Wey, Chiung-Yin Huang, Kuo-Chen Wei, and Hao-Li Liu Copyright © 2013 Po-Chun Chu et al. All rights reserved. Significance of Coronary Calcification for Prediction of Coronary Artery Disease and Cardiac Events Based on 64-Slice Coronary Computed Tomography Angiography Sun, 17 Mar 2013 15:26:50 +0000 This work aims to validate the clinical significance of coronary artery calcium score (CACS) in predicting coronary artery disease (CAD) and cardiac events in 100 symptomatic patients (aged 37–87 years, mean 62.5, 81 males) that were followed up for a mean of 5 years. Our results showed that patients with CAD and cardiac events had significantly higher CACS than those without CAD and cardiac events, respectively. The corresponding data were versus () for CAD, and versus () for cardiac events. Of 72 patients with CAD, cardiac events were found in 56 (77.7%) patients. The prevalence of cardiac events in our cohort was 13.3% for calcium score 0, 50% for score 11–100, 56% for score 101–400, 68.7% for score 401–1,000, and 75.0% for score >1000. Increased CACS (>100) was also associated with an increased frequency of multi-vessel disease. Nonetheless, 3 (20%) out of 15 patients with zero CACS had single-vessel disease. Significant correlation () was observed between CACS and CAD on a vessel-based analysis for coronary arteries. It is concluded that CACS is significantly correlated with CAD and cardiac events. Yuan-Chang Liu, Zhonghua Sun, Pei-Kwei Tsay, Tiffany Chan, I-Chang Hsieh, Chun-Chi Chen, Ming-Shien Wen, and Yung-Liang Wan Copyright © 2013 Yuan-Chang Liu et al. All rights reserved. Long-Term Left Ventricular Remodelling in Rat Model of Nonreperfused Myocardial Infarction: Sequential MR Imaging Using a 3T Clinical Scanner Thu, 04 Oct 2012 08:52:48 +0000 Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-term left ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long-term LVR after MI. Muhammad G. Saleh, Sarah-Kate Sharp, Alkathafi Alhamud, Bruce S. Spottiswoode, Andre J. W. van der Kouwe, Neil H. Davies, Thomas Franz, and Ernesta M. Meintjes Copyright © 2012 Muhammad G. Saleh et al. All rights reserved. Molecular Imaging-Guided Theranostics and Personalized Medicine Wed, 18 Jul 2012 15:17:43 +0000 Hong Zhang, Mei Tian, Enzhong Li, Yasuhisa Fujibayashi, Lie-Hang Shen, and David J. Yang Copyright © 2012 Hong Zhang et al. All rights reserved. Detection of Canonical Hedgehog Signaling in Breast Cancer by 131-Iodine-Labeled Derivatives of the Sonic Hedgehog Protein Thu, 28 Jun 2012 08:48:28 +0000 Activation of hedgehog (HH) pathway signaling is observed in many tumors. Due to a feedback loop, the HH receptor Patched (PTCH-1) is overexpressed in tumors with activated HH signaling. Therefore, we sought to radiolabel the PTCH-1 ligand sonic (SHH) for detection of cancer cells with canonical HH activity. Receptor binding of 131I-SHH was increased in cell lines with high HH pathway activation. Our findings also show that PTCH-1 receptor expression is decreased upon treatment with HH signaling inhibitors, and receptor binding of 131I-SHH is significantly decreased following treatment with cyclopamine. In vivo imaging and biodistribution studies revealed significant accumulation of 131I-SHH within tumor tissue as compared to normal organs. Tumor-to-muscle ratios were approximately 8 : 1 at 5 hours, while tumor to blood and tumor to bone were 2 : 1 and 5 : 1, respectively. Significant uptake was also observed in liver and gastrointestinal tissue. These studies show that 131I-SHH is capable of in vivo detection of breast tumors with high HH signaling. We further demonstrate that the hedgehog receptor PTCH-1 is downregulated upon treatment with hedgehog inhibitors. Our data suggests that radiolabeled SHH derivatives may provide a method to determine response to SHH-targeted therapies. Jennifer Sims-Mourtada, David Yang, Izabela Tworowska, Richard Larson, Daniel Smith, Ning Tsao, Lynn Opdenaker, Firas Mourtada, and Wendy Woodward Copyright © 2012 Jennifer Sims-Mourtada et al. All rights reserved. Effectiveness of Myocardial Contrast Echocardiography Quantitative Analysis during Adenosine Stress versus Visual Analysis before Percutaneous Therapy in Acute Coronary Pain: A Coronary Artery TIMI Grading Comparing Study Wed, 13 Jun 2012 13:42:48 +0000 The study aim was to compare two different stress echocardiography interpretation techniques based on the correlation with thrombosis in myocardial infarction (TIMI ) flow grading from acute coronary syndrome (ACS) patients. Forty-one patients with suspected ACS were studied before diagnostic coronary angiography with myocardial contrast echocardiography (MCE) at rest and at stress. The correlation of visual interpretation of MCE and TIMI flow grade was significant. The quantitative analysis (myocardial perfusion parameters: 𝐴, 𝛽, and 𝐴×𝛽) and TIMI flow grade were significant. MCE visual interpretation and TIMI flow grade had a high degree of agreement, on diagnosing myocardial perfusion abnormality. If one considers TIMI flow grade <3 as abnormal, MCE visual interpretation at rest had 73.1% accuracy with 58.2% sensitivity and 84.2% specificity and at stress had 80.4% accuracy with 76.6% sensitivity and 83.3% specificity. The MCE quantitative analysis has better accuracy with 100% of agreement with different level of TIMI flow grading. MCE quantitative analysis at stress has showed a direct correlation with TIMI flow grade, more significant than the visual interpretation technique. Further studies could measure the clinical relevance of this more objective approach to managing acute coronary syndrome patient before percutaneous coronary intervention (PCI). Lixia Yang, Yuming Mu, Luiz Augusto Quaglia, Qi Tang, Lina Guan, Chunmei Wang, and Ming Chi Shih Copyright © 2012 Lixia Yang et al. All rights reserved. In Vivo Visualization of Heterogeneous Intratumoral Distribution of Hypoxia-Inducible Factor-1𝜶 Activity by the Fusion of High-Resolution SPECT and Morphological Imaging Tests Tue, 12 Jun 2012 08:27:11 +0000 Purpose. We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α (HIF) activity in tumor tissues in vivo. Methods. We synthesized of 125I-IPOS, a 125I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of 125I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of 125I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtained in vivo SPECT-CT fusion images were compared with ex vivo images of excised tumors. Fusion imaging with MRI was also examined. Results. 125I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of 125I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of 125I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of 125I-IPOS. Conclusion. High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of 125I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activity in vivo. Hirofumi Fujii, Masayuki Yamaguchi, Kazumasa Inoue, Yasuko Mutou, Masashi Ueda, Hideo Saji, Shinae Kizaka-Kondoh, Noriyuki Moriyama, and Izumi O. Umeda Copyright © 2012 Hirofumi Fujii et al. All rights reserved. Development of 𝟗𝟗𝐦𝐓𝐜-N4-NIM for Molecular Imaging of Tumor Hypoxia Sun, 10 Jun 2012 15:26:45 +0000 The nitro group of 2-nitroimidazole (NIM) enters the tumor cells and is bioreductively activated and fixed in the hypoxia cells. 1,4,8,11-tetraazacyclotetradecane (N4) has shown to be a stable chelator for 99mTc. The present study was aimed to develop 99mTc-cyclam-2-nitroimidazole (99mTc-N4-NIM) for tumor hypoxia imaging. N4-NIM precursor was synthesized by reacting N4-oxalate and 1,3-dibromopropane-NIM, yielded 14% (total synthesis). Cell uptake of 99mTc-N4-NIM and 99mTc-N4 was obtained in 13762 rat mammary tumor cells and mesothelioma cells in 6-well plates. Tissue distribution of 99mTc-N4-NIM was evaluated in breast-tumor-bearing rats at 0.5–4 hrs. Tumor oxygen tension was measured using an oxygen probe. Planar imaging was performed in the tumor-bearing rat and rabbit models. Radiochemical purity of 99mTc-N4-NIM was >96% by HPLC. Cell uptake of 99mTc-N4-NIM was higher than 99mTc-N4 in both cell lines. Biodistribution of 99mTc-N4-NIM showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Oxygen tension in tumor tissue was 6–10 mmHg compared to 40–50 mmHg in normal muscle tissue. Planar imaging studies confirmed that the tumors could be visualized clearly with 99mTc-N4-NIM in animal models. Efficient synthesis of N4-NIM was achieved. 99mTc-N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy. Mohammad S. Ali, Fan-Lin Kong, Alex Rollo, Richard Mendez, Saady Kohanim, Daniel Lee Smith, and David J. Yang Copyright © 2012 Mohammad S. Ali et al. All rights reserved. Molecular Imaging of Mesothelioma with 99mTc-ECG and 68Ga-ECG Tue, 08 May 2012 10:44:35 +0000 We have developed ethylenedicysteine-glucosamine (ECG) as an alternative to 18F-fluoro-2-deoxy-D-glucose (18F-FDG) for cancer imaging. ECG localizes in the nuclear components of cells via the hexosamine biosynthetic pathway. This study was to evaluate the feasibility of imaging mesothelioma with 99mTc-ECG and 68Ga-ECG. ECG was synthesized from thiazolidine-4-carboxylic acid and 1,3,4,6-tetra-O-acetyl-2-amino-D-glucopyranose, followed by reduction in sodium and liquid ammonia to yield ECG (52%). ECG was chelated with 99mTc/tin (II) and 68Ga/69Ga chloride for in vitro and in vivo studies in mesothelioma. The highest tumor uptake of 99mTc-ECG is 0.47 at 30 min post injection, and declined to 0.08 at 240 min post injection. Tumor uptake (%ID/g), tumor/lung, tumor/blood, and tumor/muscle count density ratios for 99mTc-ECG (30–240 min) were 0.47±0.06 to 0.08±0.01; 0.71±0.07 to 0.85±0.04; 0.47±0.03 to 0.51±0.01, and 3.49±0.24 to 5.06±0.25; for 68Ga-ECG (15–60 min) were 0.70±0.06 to 0.92±0.08; 0.64±0.05 to 1.15±0.08; 0.42±0.03 to 0.67±0.07, and 3.84±0.52 to 7.00±1.42; for 18F-FDG (30–180 min) were 1.86±0.22 to 1.38±0.35; 3.18±0.44 to 2.92±0.34, 4.19±0.44 to 19.41±2.05 and 5.75±2.55 to 3.33±0.65, respectively. Tumor could be clearly visualized with 99mTc-ECG and 68Ga-ECG in mesothelioma-bearing rats. 99mTc-ECG and 68Ga-ECG showed increased uptake in mesothelioma, suggesting they may be useful in diagnosing mesothelioma and also monitoring therapeutic response. Yin-Han Zhang, Jerry Bryant, Fan-Lin Kong, Dong-Fang Yu, Richard Mendez, E. Edmund Kim, and David J. Yang Copyright © 2012 Yin-Han Zhang et al. All rights reserved. Effect of Low Tube Voltage on Image Quality, Radiation Dose, and Low-Contrast Detectability at Abdominal Multidetector CT: Phantom Study Mon, 23 Apr 2012 16:07:31 +0000 Purpose. To investigate the effect of low tube voltage (80 kV) on image quality, radiation dose, and low-contrast detectability (LCD) at abdominal computed tomography (CT). Materials and Methods. A phantom containing low-contrast objects was scanned with a CT scanner at 80 and 120 kV, with tube current-time product settings at 150–650 mAs. The differences between image noise, contrast-to-noise ratio (CNR), and scores of LCD obtained with 80 kV at 150–650 mAs and those obtained with 120 kV at 300 mAs were compared respectively. Results. The image noise substantially increased with low tube voltage. However, with identical dose, use of 80 kV resulted in higher CNR compared with CNR at 120 kV. There were no statistically significant difference in CNR and scores of LCD between 120 kV at 300 mAs and 80 kV at 550–650 mAs (𝑃>0.05). The relative dose delivered at 80 kV ranged from 58% at 550 mAs to 68% at 650 mAs. Conclusion. With a reduction of the tube voltage from 120 kV to 80 kV at abdominal CT, the radiation dose can be reduced by 32% to 42% without degradation of CNR and LCD. Kun Tang, Ling Wang, Rui Li, Jie Lin, Xiangwu Zheng, and Guoquan Cao Copyright © 2012 Kun Tang et al. All rights reserved. 111In-Labeled Cystine-Knot Peptides Based on the Agouti-Related Protein for Targeting Tumor Angiogenesis Wed, 11 Apr 2012 13:25:43 +0000 Agouti-related protein (AgRP) is a 4-kDa cystine-knot peptide of human origin with four disulfide bonds and four solvent-exposed loops. The cell adhesion receptor integrin 𝛼v𝛽3 is an important tumor angiogenesis factor that determines the invasiveness and metastatic ability of many malignant tumors. AgRP mutants have been engineered to bind to integrin 𝛼v𝛽3 with high affinity and specificity using directed evolution. Here, AgRP mutants 7C and 6E were radiolabeled with 111In and evaluated for in vivo targeting of tumor integrin 𝛼v𝛽3 receptors. AgRP peptides were conjugated to the metal chelator 1, 4, 7, 10-tetra-azacyclododecane- N, N, N, N-tetraacetic acid (DOTA) and radiolabeled with 111In. The stability of the radiopeptides 111In-DOTA-AgRP-7C and 111In-DOTA-AgRP-6E was tested in phosphate-buffered saline (PBS) and mouse serum, respectively. Cell uptake assays of the radiolabeled peptides were performed in U87MG cell lines. Biodistribution studies were performed to evaluate the in vivo performance of the two resulting probes using mice bearing integrin-expressing U87MG xenograft tumors. Both AgRP peptides were easily labeled with 111In in high yield and radiochemical purity (>99%). The two probes exhibited high stability in phosphate-buffered saline and mouse serum. Compared with 111In-DOTA-AgRP-6E, 111In-DOTA-AgRP-7C showed increased U87MG tumor uptake and longer tumor retention (5.74±1.60 and 1.29±0.02%ID/g at 0.5 and 24 h, resp.), which was consistent with measurements of cell uptake. Moreover, the tumor uptake of 111In-DOTA-AgRP-7C was specifically inhibited by coinjection with an excess of the integrin-binding peptidomimetic c(RGDyK). Thus, 111In-DOTA-AgRP-7C is a promising probe for targeting integrin 𝛼v𝛽3 positive tumors in living subjects. Lei Jiang, Zheng Miao, Richard H. Kimura, Adam P. Silverman, Gang Ren, Hongguang Liu, Hankui Lu, Jennifer R. Cochran, and Zhen Cheng Copyright © 2012 Lei Jiang et al. All rights reserved. Usefulness of FDG, MET and FLT-PET Studies for the Management of Human Gliomas Wed, 11 Apr 2012 12:07:27 +0000 The use of positron imaging agents such as FDG, MET, and FLT is expected to lead the way for novel applications toward efficient malignancy grading and treatment of gliomas. In this study, the usefulness of FDG, MET and FLT-PET images was retrospectively reviewed by comparing their histopathological findings. FDG, MET, and FLT-PET were performed in 27 patients with WHO grade IV, 15 patients with WHO grade III, and 12 patients with WHO grade II during 5.5 years. The resulting PET images were compared by measuring SUVs and T/N ratios (tumor to normal tissue ratios). Although there were no significant differences in FDG-PET, there were significant differences in the T/N ratios in the MET-PET between WHO grades II and IV and in the FLT-PET between the WHO grades III and IV. In glioblastoma patients, the SUVs of the areas depicted by MRI in the MET-PET were different from those SUVs in the FLT-PET. Importantly, the areas with high SUVs in both MET-PET and FLT-PET were also high in Ki-67 index and were histologically highly malignant. PET imaging is a noninvasive modality that is useful in determining a tumor area for removal as well as improving preoperative diagnosis for gliomas. Keisuke Miyake, Aya Shinomiya, Masaki Okada, Tetsuhiro Hatakeyama, Nobuyuki Kawai, and Takashi Tamiya Copyright © 2012 Keisuke Miyake et al. All rights reserved. Recent Advances in Imaging of Dopaminergic Neurons for Evaluation of Neuropsychiatric Disorders Tue, 10 Apr 2012 11:40:51 +0000 Dopamine is the most intensely studied monoaminergic neurotransmitter. Dopaminergic neurotransmission plays an important role in regulating several aspects of basic brain function, including motor, behavior, motivation, and working memory. To date, there are numerous positron emission tomography (PET) and single photon emission computed tomography (SPECT) radiotracers available for targeting different steps in the process of dopaminergic neurotransmission, which permits us to quantify dopaminergic activity in the living human brain. Degeneration of the nigrostriatal dopamine system causes Parkinson’s disease (PD) and related Parkinsonism. Dopamine is the neurotransmitter that has been classically associated with the reinforcing effects of drug abuse. Abnormalities within the dopamine system in the brain are involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Dopamine receptors play an important role in schizophrenia and the effect of neuroleptics is through blockage of dopamine D2 receptors. This review will concentrate on the radiotracers that have been developed for imaging dopaminergic neurons, describe the clinical aspects in the assessment of neuropsychiatric disorders, and suggest future directions in the diagnosis and management of such disorders. Lie-Hang Shen, Mei-Hsiu Liao, and Yu-Chin Tseng Copyright © 2012 Lie-Hang Shen et al. All rights reserved. Molecular Imaging in Tracking Tumor Stem-Like Cells Tue, 10 Apr 2012 11:08:07 +0000 Cancer remains a major public health problem in many countries. It was found to contain a subset of cancer stem cells (CSCs) that are capable of proliferation and self-renewal, and differentiation into various types of cancer cells. CSCs often display characteristics of chemotherapy resistance and radiotherapy resistance. Numerous putative biomarkers of CSCs are currently identified including CD133, CD44, CD24, ALDH (aldehyde dehydrogenase), and ABCG2. Interestingly, no single marker is exclusively expressed by CSCs. Thus, the various combinations of different biomarkers will be possible to identify CSCs, and considerable work is being done to recognize new ones. In order to demonstrate the mechanisms of resistance and response to therapy and predict the outcome as well as prognosis, the ways to track and identify CSCs will be extremely important. The technologies of molecular imaging will reveal mechanisms of cancer progression and provide visual targets for novel therapeutics. Limited studies were investigated on the detection of various types of CSCs by molecular imaging. Although the tracking of circulating CSCs is still hampered by technological challenges, personalized diagnosis and therapies of cancers are expected to be established based on increased understanding of molecular imaging of cancer stem-like cells biomarkers. Tian Xia, Han Jiang, Chenrui Li, Mei Tian, and Hong Zhang Copyright © 2012 Tian Xia et al. All rights reserved. SPECT Molecular Imaging in Parkinson's Disease Sat, 24 Mar 2012 20:08:13 +0000 Parkinson's disease (PD) is a common disorder, and the diagnosis of Parkinson's disease is clinical and relies on the presence of characteristic motor symptoms. The accuracy of the clinical diagnosis of PD is still limited. Functional neuroimaging using SPECT technique is helpful in patients with first signs of parkinsonism. The changes detected may reflect the disease process itself and/or compensatory responses to the disease, or they may arise in association with disease- and/or treatment-related complications. This paper addresses the value of SPECT in early differential diagnosis of PD and its potential as a sensitive tool to assess the pathophysiology and progression, as well as the therapeutic efficacy of PD. Ling Wang, Qi Zhang, Huanbin Li, and Hong Zhang Copyright © 2012 Ling Wang et al. All rights reserved. Molecular Imaging in Therapeutic Efficacy Assessment of Targeted Therapy for Nonsmall Cell Lung Cancer Wed, 21 Mar 2012 16:04:43 +0000 Membrane distillation is a thermally driven membrane process for seawater desalination and purification at moderate temperatures and pressures. A hydrophobic micro-porous membrane is used in this process, which separates hot and cold water, allowing water vapor to pass through; while restricting the movement of liquid water, due to its hydrophobic nature. This paper provides an experimental investigation of heat and mass transfer in tubular membrane module for water desalination. Different operating parameters have been examined to determine the mass transport mechanism of water vapor. Based on the experimental results, the effects of operating parameters on permeate flux and the heat transfer analysis have been presented and discussed in details. Yanni Hu, Mei Tian, and Hong Zhang Copyright © 2012 Yanni Hu et al. All rights reserved. Efficiency of Ferritin as an MRI Reporter Gene in NPC Cells Is Enhanced by Iron Supplementation Tue, 20 Mar 2012 13:07:54 +0000 Background. An emerging MRI reporter, ferritin heavy chain (FTH1), is recently applied to enhance the contrast and increase the sensitivity of MRI in the monitoring of solid tumors. However, FTH1-overexpression-related cytotoxicity is required to be explored. Methods. By using the Tet-Off system, FTH1 overexpression was semi-quantitativiely and dynamicly regulated by doxycycline in a NPC cell line. Effects of FTH1 overexpression on the proliferation, cytotoxicity, apoptosis and migration of NPC cells were investigated in vitro, and MR relaxation rate was measured in vitro and in vivo. Results. In vitro and in vivo overexpression of FTH1 significantly increased the transverse relaxivity (𝑅2), which could be enhanced by iron supplementation. In vitro, overexpression of FTH1 reduced cell growth and migration, which were not reduced by iron supplementation. Furthermore, cells were subcutaneously inoculated into the nude mice. Results showed FTH1 overexpression decreased tumor growth in the absence of iron supplementation but not in the presence of iron supplementation. Conclusion. To maximize 𝑅2 and minimize the potential adverse effects, supplementation of iron at appropriate dose is recommended during the application of FTH1 as a reporter gene in the monitoring of NPC by MRI. Yupeng Feng, Qicai Liu, Junfeng Zhu, Fukang Xie, and Li Li Copyright © 2012 Yupeng Feng et al. All rights reserved. Multiple Metastasis-Like Bone Lesions in Scintigraphic Imaging Thu, 15 Mar 2012 13:34:41 +0000 Multiple benign osteolytic lesions are very hard to differentiate from disseminated bone metastasis. Whole-body bone scintigraphy (WBBS) with technetium-99m methylene diphosphonate (Tc-99m MDP) demonstrates multiple lesions with increased uptake in any bone involved. Even combined with medical history and multiple imaging results, such as MRI and CT, the clinical diagnosis of metastasis lesion remains as a challenge. These clinical characteristics are similar to multiple malignant bone metastases and therefore affect the following treatment procedures. In this paper, we analyzed multiple benign osteolytic lesions, like eosinophilic granuloma (EG), multiple myeloma (MM), disseminated tuberculosis, fibrous dysplasia, or enchondroma, occurring in our daily clinical work and concluded that additional attention should be paid before giving the diagnosis of multiple bone metastases. Ying Zhang, Chunlei Zhao, Hongbiao Liu, Haifeng Hou, and Hong Zhang Copyright © 2012 Ying Zhang et al. All rights reserved. Reduced Striatal Dopamine Transporters in People with Internet Addiction Disorder Tue, 13 Mar 2012 15:43:00 +0000 In recent years, internet addiction disorder (IAD) has become more prevalent worldwide and the recognition of its devastating impact on the users and society has rapidly increased. However, the neurobiological mechanism of IAD has not bee fully expressed. The present study was designed to determine if the striatal dopamine transporter (DAT) levels measured by 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) brain scans were altered in individuals with IAD. SPECT brain scans were acquired on 5 male IAD subjects and 9 healthy age-matched controls. The volume (V) and weight (W) of bilateral corpus striatum as well as the 99mTc-TRODAT-1 uptake ratio of corpus striatum/the whole brain (Ra) were calculated using mathematical models. It was displayed that DAT expression level of striatum was significantly decreased and the V, W, and Ra were greatly reduced in the individuals with IAD compared to controls. Taken together, these results suggest that IAD may cause serious damages to the brain and the neuroimaging findings further illustrate IAD is associated with dysfunctions in the dopaminergic brain systems. Our findings also support the claim that IAD may share similar neurobiological abnormalities with other addictive disorders. Haifeng Hou, Shaowe Jia, Shu Hu, Rong Fan, Wen Sun, Taotao Sun, and Hong Zhang Copyright © 2012 Haifeng Hou et al. All rights reserved. PET/CT in the Staging of the Non-Small-Cell Lung Cancer Wed, 07 Mar 2012 13:36:07 +0000 Lung cancer is a common disease and the leading cause of cancer-related death in many countries. Precise staging of patients with non-small-cell lung cancer plays an important role in determining treatment strategy and prognosis. Positron emission tomography/computed tomography (PET/CT), combining anatomic information of CT and metabolic information of PET, is emerging as a potential diagnosis and staging test in patients with non-small-cell lung cancer (NSCLC). The purpose of this paper is to discuss the value of integrated PET/CT in the staging of the non-small-cell lung cancer and its health economics. Fangfang Chao and Hong Zhang Copyright © 2012 Fangfang Chao and Hong Zhang. All rights reserved. Development of Tyrosine-Based Radiotracer 𝟗𝟗𝐦Tc-N4-Tyrosine for Breast Cancer Imaging Mon, 05 Mar 2012 13:58:32 +0000 The purpose of this study was to develop an efficient way to synthesize 99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-tyrosine (99mTc-N4-Tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Precursor N4-Tyrosine was synthesized using a 5-step procedure, and its total synthesis yield was 38%. It was successfully labeled with 99mTc with high radiochemical purity (>95%). Cellular uptake of 99mTc-N4-Tyrosine was much higher than that of 99mTc-N4 and the clinical gold standard 18F-2-deoxy-2-fluoro-glucose (18F-FDG) in rat breast tumor cells in vitro. Tissue uptake and dosimetry estimation in normal rats revealed that 99mTc-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that although 99mTc-N4-Tyrosine appeared to be inferior to 18F-FDG in distinguishing breast tumor tissue from chemical-induced inflammatory tissue, it had high tumor-to-muscle uptake ratios and could detect breast tumors clearly by planar scintigraphic imaging. 99mTc-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging. Fan-Lin Kong, Mohammad S. Ali, Alex Rollo, Daniel L. Smith, Yinhan Zhang, Dong-Fang Yu, and David J. Yang Copyright © 2012 Fan-Lin Kong et al. All rights reserved. Molecular Image-Guided Theranostic and Personalized Medicine Sun, 03 Jul 2011 10:00:05 +0000 Hong Zhang, Mei Tian, Carrio Ignasi, Zhen Cheng, Lie-Hang Shen, and David J. Yang Copyright © 2011 Hong Zhang et al. All rights reserved. Comparison of Cell Proliferation, Protein, and Glucose Metabolism in Musculoskeletal Tumors in a PET Study Thu, 16 Jun 2011 18:46:17 +0000 11C-choline and 18F-FAMT are known to correlate with tumor cell proliferation and amino acid metabolism. We investigated the ability of 11C-Choline and 18F-FAMT PET in diagnosis of musculoskeletal tumors in thirty-six patients in comparison of 18F-FDG PET. 11C-Choline and 18F-FDG PET were positive in all the malignant tumors (𝑛=13), whereas 18F-FAMT was positive in 11 tumors. The mean SUVs for malignant tumors were significantly higher than those for benign lesions in all three tracers imaging. A moderate correlation was found between 11C-Choline and 18F-FDG (𝑟=0.540, 𝑃<.05), or 18F-FAMT and FDG (𝑟=0.596, 𝑃<.05). The diagnostic sensitivity and specificity for malignancy were 91.7% and 71.4%, respectively, using 11C-choline with a SUV cut-off of 2.69. The sensitivity and specificity of 18F-FAMT for malignancy were 66.7% and 85.7%, respectively, using a SUV cut-off of 1.26. For 18F-FDG, using a SUV cut-off of 2.77, the sensitivity and specificity were 83.3% and 71.4%, respectively. According to ROC analysis, the ROC curves for 11C-Choline, 18F-FAMT, and 18F-FDG were 0.855, 0.734, and 0.847, respectively. 11C-Choline PET is superior in the visualization of musculoskeletal tumors with high contrast imaging, whereas the combination of 18F-FAMT and 18F-FDG PET provides valuable information for the preoperative planning in patients with musculoskeletal tumors. Mei Tian, Hong Zhang, and Keigo Endo Copyright © 2011 Mei Tian et al. All rights reserved. Chemiluminescent Nanomicelles for Imaging Hydrogen Peroxide and Self-Therapy in Photodynamic Therapy Wed, 15 Jun 2011 08:33:51 +0000 Hydrogen peroxide is a signal molecule of the tumor, and its overproduction makes a higher concentration in tumor tissue compared to normal tissue. Based on the fact that peroxalates can make chemiluminescence with a high efficiency in the presence of hydrogen peroxide, we developed nanomicelles composed of peroxalate ester oligomers and fluorescent dyes, called peroxalate nanomicelles (POMs), which could image hydrogen peroxide with high sensitivity and stability. The potential application of the POMs in photodynamic therapy (PDT) for cancer was also investigated. It was found that the PDT-drug-loaded POMs were sensitive to hydrogen peroxide, and the PDT drug could be stimulated by the chemiluminescence from the reaction between POMs and hydrogen peroxide, which carried on a self-therapy of the tumor without the additional laser light resource. Rui Chen, Luzhong Zhang, Jian Gao, Wei Wu, Yong Hu, and Xiqun Jiang Copyright © 2011 Rui Chen et al. All rights reserved. In Vitro Study on Apoptosis Induced by Strontium-89 in Human Breast Carcinoma Cell Line Thu, 09 Jun 2011 18:09:10 +0000 Many radiopharmaceuticals used for medical diagnosis and therapy are beta emitters; however, the mechanism of the cell death caused by beta-irradiation is not well understood. The objective of this study was to investigate the apoptosis of human breast carcinoma MCF-7 cell lines induced by Strontium-89 (89Sr) and its regulation and control mechanism. High-metastatic Breast Carcinoma MCF-7 cells were cultured in vitro using 89Sr with different radioactive concentration. The inhibition rate of cell proliferation was measured by MTT color matching method. The cell cycle retardation, apoptosis conditions, mitochondrion transmembrane potential difference and Fas expression were tested and analyzed. The genes P53 and bcl-2 expressions was also analyzed using immunity histochemical analysis. After being induced by 89Sr with various of radioactive concentration, it was found that the inhibition of cell proliferation of MCF-7 cells was obviously, the retardation of cell cycle occurred mainly in G2-M. It was also found that the obvious apoptosis occurred after being induced by 89Sr, the highest apoptosis rate reached 46.28%. The expressions of Fas acceptor and P53 gene increased, while bcl-2 gene expression decreasesd. These findings demonstrate that in the ranges of a certain radioactive concentration, the inhibition rate of MCF-7 cell proliferation and retardation of cell cycle had positive correlation with the concentration of 89Sr. And the mitochondrion transmembrane potential decrease would induce the apoptosis of MCF-7 cell notably, which were controlled by P53 and bcl-2 genes, involved with the Fas acceptor. Cheng Wang, Jing Wang, Han Jiang, Min Zhu, Baoguo Chen, and Weiguang Bao Copyright © 2011 Cheng Wang et al. All rights reserved. Direct Determination of ECD in ECD Kit: A Solid Sample Quantitation Method for Active Pharmaceutical Ingredient in Drug Product Thu, 09 Jun 2011 18:03:55 +0000 Technetium-99m ethyl cysteinate dimer (Tc-99m-ECD) is an essential imaging agent used in evaluating the regional cerebral blood flow in patients with cerebrovascular diseases. Determination of active pharmaceutical ingredient, that is, L-Cysteine, N, N′-1,2-ethanediylbis-, diethyl ester, dihydrochloride (ECD) in ECD Kit is a relevant requirement for the pharmaceutical quality control in processes of mass fabrication. We here presented a direct solid sample determination method of ECD in ECD Kit without sample dissolution to avoid the rapid degradation of ECD. An elemental analyzer equipped with a nondispersive infrared detector and a calibration curve of coal standard was used for the quantitation of sulfur in ECD Kit. No significant matrix effect was found. The peak area of coal standard against the amount of sulfur was linear over the range of 0.03–0.10 mg, with a correlation coefficient (𝑟) of 0.9993. Method validation parameters were achieved to demonstrate the potential of this method. Ming-Yu Chao, Kung-Tien Liu, Yi-Chih Hsia, Mei-Hsiu Liao, and Lie-Hang Shen Copyright © 2011 Ming-Yu Chao et al. All rights reserved. Ursolic Acid Inhibits Proliferation and Induces Apoptosis of Cancer Cells In Vitro and In Vivo Mon, 30 May 2011 09:52:57 +0000 The aims of the study are to explore the effect of ursolic acid (UA) on the growth of gastric cancer cell line BGC-803 and hepatocellular cancer cell H22 xenograft and to understand the mechanism. UA inhibits growth of BGC-803 cells in vitro in dose-dependent and time-dependent manner. Treated with UA in vivo, tumor cells can be arrested to G0/G1 stage. The apoptotic rate was significantly increased in tumor cells treated with UA both in vitro and in vivo. DNA fragmentation was found in BGC-803 cells exposed to UA. UA activated caspase-3, -8, and -9 and down regulated expression of Bcl-2 in BGC-803 cells. The expression of caspase-3 and -8 was elevated in tumor cells from xenograft treated with UA. 18F-FLT PET-CT imaging confirmed tumor model and UA effectiveness. Our results indicated that UA inhibits growth of tumor cells both in vitro and in vivo by decreasing proliferation of cells and inducing apoptosis. Xuemei Wang, Fan Zhang, Ling Yang, Ying Mei, Hai Long, Xiaowen Zhang, Jialing Zhang, Qimuge-Suyila, and Xiulan Su Copyright © 2011 Xuemei Wang et al. All rights reserved. Molecular Imaging, Pharmacokinetics, and Dosimetry of 111In-AMBA in Human Prostate Tumor-Bearing Mice Tue, 24 May 2011 10:14:28 +0000 Molecular imaging with promise of personalized medicine can provide patient-specific information noninvasively, thus enabling treatment to be tailored to the specific biological attributes of both the disease and the patient. This study was to investigate the characterization of DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA) in vitro, MicroSPECT/CT imaging, and biological activities of 111In-AMBA in PC-3 prostate tumor-bearing SCID mice. The uptake of 111In-AMBA reached highest with 3.87±0.65% ID/g at 8 h. MicroSPECT/CT imaging studies suggested that the uptake of 111In-AMBA was clearly visualized between 8 and 48 h postinjection. The distribution half-life (t1/2α) and the elimination half-life (t1/2β) of 111In-AMBA in mice were 1.53 h and 30.7 h, respectively. The 𝐶max and AUC of 111In-AMBA were 7.57% ID/g and 66.39 h∗% ID/g, respectively. The effective dose appeared to be 0.11 mSv/MBq-1. We demonstrated a good uptake of 111In-AMBA in the GRPR-overexpressed PC-3 tumor-bearing SCID mice. 111In-AMBA is a safe, potential molecular image-guided diagnostic agent for human GRPR-positive tumors, ranging from simple and straightforward biodistribution studies to improve the efficacy of combined modality anticancer therapy. Chung-Li Ho, I-Hsiang Liu, Yu-Hsien Wu, Liang-Cheng Chen, Chun-Lin Chen, Wan-Chi Lee, Cheng-Hui Chuang, Te-Wei Lee, Wuu-Jyh Lin, Lie-Hang Shen, and Chih-Hsien Chang Copyright © 2011 Chung-Li Ho et al. All rights reserved. Protein Expression of Mesenchymal Stem Cells after Transfection of pcDNA3.1−-hVEGF165 by Ultrasound-Targeted Microbubble Destruction Thu, 19 May 2011 11:39:59 +0000 Ultrasound-targeted microbubble destruction (UTMD) has been proposed as a new technique for organ-specific gene transfer and drug delivery. This study was performed to investigate the effect of UTMD on marrow mesenchymal stem cells (MSCs) transfected with pcDNA3.1−-hVEGF165.pcDNA3.1−-hVEGF165 were transfected into the third passage of MSCs, with or without UTMD under different ultrasound conditions. Protein expression was quantified by hVEGF165-ELISA kit after transfection for 24, 48, and 72 hours. UTMD-mediated transfection of MSCs yielded a significant protein expression. UTMD of mechanic index (MI) 0.6 for 90 seconds led to the highest level of protein expression. Zhaoxia Pu, Xiangdong You, Qiyuan Xu, Feng Gao, Xiaojie Xie, Hong Zhang, and Wang Jian'an Copyright © 2011 Zhaoxia Pu et al. All rights reserved. Technetium-99m-Labeled Autologous Serum Albumin: A Personal-Exclusive Source of Serum Component Thu, 28 Apr 2011 08:57:16 +0000 Technetium-99m human serum albumin (99mTc-HSA) is an important radiopharmaceutical required in nuclear medicine studies. However, the risk of transfusion-transmitted infection remains a major safety concern. Autopreparation of serum component acquired from patient provides a “personal-exclusive” source for radiolabeling. This paper is to evaluate the practicality of on-site elusion and subsequent radiolabeling efficacy for serum albumin. Results showed that the autologous elute contained more albumin fraction than serum without extraction procedure. Good radiochemical purity and stability were demonstrated after radiolabeling. Biodistribution study showed that labeled albumin accumulated immediately in the lung, liver, and kidney. It was cleared steadily and excreted in the urine. The biologic half-life was defined, and all samples passed the pyrogenicity and sterility tests. In conclusion, autoalbumin could be extracted and radiolabeled properly in a nuclear medicine setting. Moreover, the risk of transfusion-transmitted infection associated with nonautologous, multisource 99mTc-HSA agents can be reduced. Yuh-Feng Wang, Yi-Chun Chen, Dian-Kun Li, and Mei-Hua Chuang Copyright © 2011 Yuh-Feng Wang et al. All rights reserved. Investigation of a Potential Scintigraphic Tracer for Imaging Apoptosis: Radioiodinated Annexin V-Kunitz Protease Inhibitor Fusion Protein Wed, 27 Apr 2011 13:47:28 +0000 Radiolabeled annexin V (ANV) has been widely used for imaging cell apoptosis. Recently, a novel ANV-Kunitz-type protease inhibitor fusion protein, ANV-6L15, was found to be a promising probe for improved apoptosis detection based on its higher affinity to phosphatidylserine (PS) compared to native ANV. The present paper investigates the feasibility of apoptosis detection using radioiodinated ANV-6L15. Native ANV and ANV-6L15 were labeled with iodine-123 and iodine-125 using Iodogen method. The binding between the radioiodinated proteins and erythrocyte ghosts or chemical-induced apoptotic cells was examined. ANV-6L15 can be radioiodinated with high yield (40%−60%) and excellent radiochemical purity (>95%). 123I-ANV-6L15 exhibited a higher binding ratio to erythrocyte ghosts and apoptotic cells compared to 123I-ANV. The biodistribution of 123I-ANV-6L15 in mice was also characterized. 123I-ANV-6L15 was rapidly cleared from the blood. High uptake in the liver and the kidneys may limit the evaluation of apoptosis in abdominal regions. Our data suggest that radiolabled ANV-6L15 may be a better scintigraphic tracer than native ANV for apoptosis detection. Mei-Hsiu Liao, Tong-Rong Jan, Chao-Chih Chiang, Kuo-Chen Yen, Tse-Zung Liao, Ming-Wei Chen, Chin-Wen Chi, Tze-Chein Wun, Tzu-Chen Yen, and Shiaw-Pyng Wey Copyright © 2011 Mei-Hsiu Liao et al. All rights reserved. The Role of Molecular Imaging in the Diagnosis and Management of Neuropsychiatric Disorders Tue, 12 Apr 2011 15:40:08 +0000 Neuropsychiatric disorders are becoming a major socioeconomic burden to modern society. In recent years, a dramatic expansion of tools has facilitated the study of the molecular basis of neuropsychiatric disorders. Molecular imaging has enabled the noninvasive characterization and quantification of biological processes at the cellular, tissue, and organism levels in intact living subjects. This technology has revolutionized the practice of medicine and has become critical to quality health care. New advances in research on molecular imaging hold promise for personalized medicine in neuropsychiatric disorders, with adjusted therapeutic doses, predictable responses, reduced adverse drug reactions, early diagnosis, and personal health planning. In this paper, we discuss the development of radiotracers for imaging dopaminergic, serotonergic, and noradrenergic systems and β-amyloid plaques. We will underline the role of molecular imaging technologies in various neuropsychiatric disorders, describe their unique strengths and limitations, and suggest future directions in the diagnosis and management of neuropsychiatric disorders. Lie-Hang Shen, Yu-Chin Tseng, Mei-Hsiu Liao, and Ying-Kai Fu Copyright © 2011 Lie-Hang Shen et al. All rights reserved. Brown Adipose Tissue Can Be Activated or Inhibited within an Hour before 18F-FDG Injection: A Preliminary Study with MicroPET Sun, 10 Apr 2011 11:39:22 +0000 Brown adipose tissue (BAT) is emerging as a potential target for treating human obesity. It has been indicated that BAT is rich in innervations of sympathetic nerve control. Using 18F-FDG microPET imaging, this study aims at evaluating how factors related to sympathetic activation/inhibition changed BAT metabolism of mice. BAT 18F-FDG uptake were semiquantitatively evaluated in different groups of mice under temperature (cold or warm stimulus) or pharmacological interventions (norepinephrine, epinephrine, isoprenaline, or propranolol) and were compared with the corresponding controls. It was found that BAT activation can be stimulated by cold exposure (), norepinephrine (), or both () within an hour before 18F-FDG injection and can also be alleviated by warming up () or propranolol lavage (). This preliminary study indicated that BAT function could be evaluated by 18F-FDG PET imaging through short-term interventions, which paved the way for further investigation of the relationship between human obesity and BAT dysfunction. Chenxi Wu, Wuying Cheng, Haiqun Xing, Yonghong Dang, Fang Li, and Zhaohui Zhu Copyright © 2011 Chenxi Wu et al. All rights reserved. Synthesis and Evaluation of Amino Acid-Based Radiotracer 99mTc-N4-AMT for Breast Cancer Imaging Thu, 07 Apr 2011 15:56:25 +0000 Purpose. This study was to develop an efficient synthesis of 99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]--methyl tyrosine (99mTc-N4-AMT) and evaluate its potential in cancer imaging. Methods. N4-AMT was synthesized by reacting N4-oxalate and 3-bromopropyl AMT (N-BOC, ethyl ester). In vitro cellular uptake kinetics of 99mTc-N4-AMT was assessed in rat mammary tumor cells. Tissue distribution of the radiotracer was determined in normal rats at 0.5–4 h, while planar imaging was performed in mammary tumor-bearing rats at 30–120 min. Results. The total synthesis yield of N4-AMT was 14%. Cellular uptake of 99mTc-N4-AMT was significantly higher than that of 99mTc-N4. Planar imaging revealed that 99mTc-N4-AMT rendered greater tumor/muscle ratios than 99mTc-N4. Conclusions. N4-AMT could be synthesized with a considerably high yield. Our in vitro and in vivo data suggest that 99mTc-N4-AMT, a novel amino acid-based radiotracer, efficiently enters breast cancer cells, effectively distinguishes mammary tumors from normal tissues, and thus holds the promise for breast cancer imaging. Fan-Lin Kong, Mohammad S. Ali, Yinhan Zhang, Chang-Sok Oh, Dong-Fang Yu, Mithu Chanda, and David J. Yang Copyright © 2011 Fan-Lin Kong et al. All rights reserved. Diagnostic Value of I-131 NP-59 SPECT/CT Scintigraphy in Patients with Subclinical or Atypical Features of Primary Aldosteronism Thu, 07 Apr 2011 15:35:43 +0000 Accumulating evidence has shown the adverse effect of long-term hyperaldosteronism on cardiovascular morbidity that is independent of blood pressure. However, the diagnosis of primary aldosteronism (PA) remains a challenge for patients who present with subtle or atypical features or have chronic kidney disease (CKD). SPECT/CT has proven valuable in the diagnosis of a number of conditions. The aim of this study was to determine the usefulness of I-131 NP-59 SPECT/CT in patients with atypical presentations of PA and in those with CKD. The records of 15 patients with PA were retrospectively analyzed. NP-59 SPECT/CT was able to identify adrenal lesion(s) in CKD patients with suspected PA. Patients using NP-59 SPECT/CT imaging, compared with those not performing this procedure, significantly featured nearly normal serum potassium levels, normal aldosterone-renin ratio, and smaller adrenal size on CT and pathological examination and tended to feature stage 1 hypertension and non-suppressed plasma renin activity. These findings show that noninvasive NP-59 SPECT/CT is a useful tool for diagnosis in patients with subclinical or atypical features of PA and those with CKD. Yi-Chun Chen, Yu-Chieh Su, Chang-Kuo Wei, Jainn-Shiun Chiu, Chih-En Tseng, Shao-Jer Chen, and Yuh-Feng Wang Copyright © 2011 Yi-Chun Chen et al. All rights reserved. Development of 68Ga-Glycopeptide as an Imaging Probe for Tumor Angiogenesis Thu, 07 Apr 2011 10:29:24 +0000 Objective. This study was aimed to study tissue distribution and tumor imaging potential of 68Ga-glycopeptide (GP) in tumor-bearing rodents by PET. Methods. GP was synthesized by conjugating glutamate peptide and chitosan. GP was labeled with 68Ga chloride for in vitro and in vivo studies. Computer outlined region of interest (counts per pixel) of the tumor and muscle (at the symmetric site) was used to determine tumor-to-muscle count density ratios. To ascertain the feasibility of 68Ga-GP in tumor imaging in large animals, PET/CT imaging of 68Ga-GP and 18F-FDG were conducted in New Zealand white rabbits bearing VX2 tumors. Standard uptake value of tumors were determined by PET up to 45 min. To determine blood clearance and half-life of 68Ga-GP, blood samples were collected from 10 seconds to 20 min. Results. Radiochemical purity of 68Ga-GP determined by instant thin-layer chromatography was >95%. Tumor uptake values (SUV) for 68Ga-GP and 18F-FDG in New Zealand white rabbits bearing VX2 tumors were 3.25 versus 7.04. PET images in tumor-bearing rats and rabbits confirmed that 68Ga-GP could assess tumor uptake. From blood clearance curve, the half-life of 68Ga-GP was 1.84 hr. Conclusion Our data indicate that it is feasible to use 68Ga-GP to assess tumor angiogenesis. Ning Tsao, Chau-Hui Wang, Li-Jane Her, Kai-Yuan Tzen, Jing-Yi Chen, Dong-Fang Yu, and David J. Yang Copyright © 2011 Ning Tsao et al. All rights reserved. Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy Tue, 03 Aug 2010 07:57:35 +0000 Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers being able to deliver radionuclide payloads in a site or molecular selective manner to improve the efficacy and safety of cancer imaging and therapy. Radionuclides of auger electron-, -, -, and -radiation emitters have been surface-bioconjugated or after-loaded in nanoparticles to improve the efficacy and reduce the toxicity of cancer imaging and therapy in preclinical and clinical studies. This article provides a brief overview of current status of applications, advantages, problems, up-to-date research and development, and future prospects of nanotargeted radionuclides in cancer nuclear imaging and radiotherapy. Passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy are reviewed and summarized. Research on combing different modes of selective delivery of radionuclides through nanocarriers targeted delivery for tumor imaging and therapy offers the new possibility of large increases in cancer diagnostic efficacy and therapeutic index. However, further efforts and challenges in preclinical and clinical efficacy and toxicity studies are required to translate those advanced technologies to the clinical applications for cancer patients. Gann Ting, Chih-Hsien Chang, Hsin-Ell Wang, and Te-Wei Lee Copyright © 2010 Gann Ting et al. All rights reserved. Bioimaging of Nucleolin Aptamer-Containing 5-(N-benzylcarboxyamide)-2′-deoxyuridine More Capable of Specific Binding to Targets in Cancer Cells Mon, 01 Mar 2010 08:42:26 +0000 Chemically modified nucleotides have been developed and applied into SELEX procedure to find a novel type of aptamers to fit with targets of interest. In this study, we directly performed chemical modification of 5-(-benzylcarboxyamide)--deoxyuridine (called 5-BzdU) in the AS1411 aptamer, which binds to the nucleolin protein expressed in cancer cells. Forty-seven compounds of AS1411-containing Cy3-labeled 5-BzdU (called Cy3-(5-BzdU)-modified-AS1411) were synthesized by randomly substituting thymidines one to twelve in AS1411 with Cy3-labeled 5-BzdU. Both statistically quantified fluorescence measurements and confocal imaging analysis demonstrated at least three potential compounds of interest: number 12, 29 and 41 that significantly increased the targeting affinity to cancer cells but no significant activity from normal healthy cells. These results suggest that the position and number of substituents in AS1411 are critical parameters to improve the aptamer function. In this study, we demonstrated that chemical modification of the existing aptamers enhanced the binding and targeting affinity to targets of interest without additional SELEX procedures. Kyue Yim Lee, Hyungu Kang, Sung Ho Ryu, Dong Soo Lee, Jung Hwan Lee, and Soonhag Kim Copyright © 2010 Kyue Yim Lee et al. All rights reserved.