BioMed Research International: Molecular Imaging The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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 (𝑃=1.96×10−4), norepinephrine (𝑃=.002), or both (𝑃=2.19×10−6) within an hour before 18F-FDG injection and can also be alleviated by warming up (𝑃=.001) or propranolol lavage (𝑃=.027). 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]-𝛼-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-, 𝛼-, 𝛽-, and 𝛾-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-(𝑁-benzylcarboxyamide)-2-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.