International Journal of Molecular Imaging http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Comparison of 99mTc-Tetrofosmin and 99mTc-Sestamibi Uptake in Glioma Cell Lines: The Role of P-Glycoprotein Expression Mon, 10 Nov 2014 14:00:08 +0000 http://www.hindawi.com/journals/ijmi/2014/471032/ Tc-Tetrofosmin (Tc-TF) and Tc-Sestamibi (Tc-MIBI) are SPECT tracers that have been used for brain tumor imaging. Tumor’s multidrug resistance phenotype, namely, P-glycoprotein (p-gp), and the multidrug resistance related proteins (MRPs) expression have been suggested to influence both tracers’ uptake. In the present study we set out to compare Tc-MIBI uptake in high-grade glioma cell lines and to investigate the influence of gliomas p-gp expression on both tracers’ uptake. We used four glioma cell lines (U251MG, A172, U87MG, and T98G). The expression of p-gp protein was evaluated by flow cytometry. Twenty μCi (7.4·105 Bq) of Tc-TF and Tc-MIBI were used. The radioactivity in the cellular lysate was measured with a dose calibrator. P-gp was significantly expressed only in the U251MG cell line (). In all gliomas cell lines (U251MG, U87MG, A172, and T98G) the Tc-TF uptake was significantly higher than Tc-sestamibi. The U251MG cell line, in which significant p-gp expression was documented, exhibited the strongest uptake difference. Tc-TF uptake was higher than Tc-MIBI in all studied high-grade glioma cell lines. Thus, Tc-TF may be superior to Tc-MIBI for glioma imaging in vivo. George A. Alexiou, Xanthi Xourgia, Evrysthenis Vartholomatos, Spyridon Tsiouris, John A. Kalef-Ezra, Andreas D. Fotopoulos, and Athanasios P. Kyritsis Copyright © 2014 George A. Alexiou et al. All rights reserved. Beneficial Effect of Glucose Control on Atherosclerosis Progression in Diabetic ApoE−/− Mice: Shown by Rage Directed Imaging Mon, 14 Apr 2014 08:16:59 +0000 http://www.hindawi.com/journals/ijmi/2014/695391/ Objective. Receptor for advanced glycated endproducts (RAGE) plays an important role in atherogenesis in diabetes. We imaged RAGE to investigate the effect of glucose control to suppress RAGE and reduce atherosclerosis in apolipoprotein E null (apoE−/−) diabetic mice. Methods and Results. Thirty-three apoE−/− mice received streptozotocin and 6 weeks later 15 began treatment with insulin implants. Blood glucose measurements during study averaged: 140 ± 23 mg/dL (treated) and 354 ± 14 mg/dL (untreated). After 15 wk 30 mice were injected with ). Conclusions. These results support the importance of suppressing RAGE to reduce atherosclerotic complications of diabetes and value of molecular imaging to assess treatment effect. Yared Tekabe, Maria Kollaros, Qing Li, Geping Zhang, Chong Li, Ann Marie Schmidt, and Lynne L. Johnson Copyright © 2014 Yared Tekabe et al. All rights reserved. Lyophilized Kit for the Preparation of the PET Perfusion Agent [68Ga]-MAA Mon, 31 Mar 2014 11:57:41 +0000 http://www.hindawi.com/journals/ijmi/2014/269365/ Rapid developments in the field of medical imaging have opened new avenues for the use of positron emitting labeled microparticles. The radioisotope used in our research was 68Ga, which is easy to obtain from a generator and has good nuclear properties for PET imaging. Methods. Commercially available macroaggregated albumin (MAA) microparticles were suspended in sterile saline, centrifuged to remove the free albumin and stannous chloride, relyophilized, and stored for later labeling with 68Ga. Labeling was performed at different temperatures and times. 68Ga purification settings were also tested and optimized. Labeling yield and purity of relyophilized MAA microparticles were compared with those that were not relyophilized. Results. MAA particles kept their original size distribution after relyophilization. Labeling yield was 98% at 75°C when a 68Ga purification system was used, compared to 80% with unpurified 68Ga. Radiochemical purity was over 97% up to 4 hours after the labeling. The relyophilized MAA and labeling method eliminate the need for centrifugation purification of the final product and simplify the labeling process. Animal experiments demonstrated the high in vivo stability of the obtained PET agent with more than 95% of the activity remaining in the lungs after 4 hours. Alejandro Amor-Coarasa, Andrew Milera, Denny Carvajal, Seza Gulec, and Anthony J. McGoron Copyright © 2014 Alejandro Amor-Coarasa et al. All rights reserved. Longitudinal Imaging of Cancer Cell Metastases in Two Preclinical Models: A Correlation of Noninvasive Imaging to Histopathology Mon, 03 Mar 2014 00:00:00 +0000 http://www.hindawi.com/journals/ijmi/2014/102702/ Metastatic spread is the leading cause of death from cancer. Early detection of cancer at primary and metastatic sites by noninvasive imaging modalities would be beneficial for both therapeutic intervention and disease management. Noninvasive imaging modalities such as bioluminescence (optical), positron emission tomography (PET)/X-ray computed tomography (CT), and magnetic resonance imaging (MRI) can provide complementary information and accurately measure tumor growth as confirmed by histopathology. Methods. We validated two metastatic tumor models, MDA-MD-231-Luc and B16-F10-Luc intravenously injected, and 4T1-Luc cells orthotopically implanted into the mammary fat pad. Longitudinal whole body bioluminescence imaging (BLI) evaluated metastasis, and tumor burden of the melanoma cell line (B16-F10-Luc) was correlated with (PET)/CT and MRI. In addition, ex vivo imaging evaluated metastasis in relevant organs and histopathological analysis was used to confirm imaging. Results. BLI revealed successful colonization of cancer cells in both metastatic tumor models over a 4-week period. Furthermore, lung metastasis of B16-F10-Luc cells imaged by PET/CT at week four showed a strong correlation () with histopathology. The presence and degree of metastasis as determined by imaging correlated () well with histopathology findings. Conclusions. We validated two metastatic tumor models by longitudinal noninvasive imaging with good histopathology correlation. Pavan P. Adiseshaiah, Nimit L. Patel, Lilia V. Ileva, Joseph D. Kalen, Diana C. Haines, and Scott E. McNeil Copyright © 2014 Pavan P. Adiseshaiah et al. All rights reserved. Feasibility and Merits of Performing Preclinical Imaging on Clinical Radiology and Nuclear Medicine Systems Mon, 30 Dec 2013 18:16:20 +0000 http://www.hindawi.com/journals/ijmi/2013/923823/ Aim. Researchers have limited access to systems dedicated to imaging small laboratory animals. This paper aims to investigate the feasibility and merits of performing preclinical imaging on clinical systems. Materials and Methods. Scans were performed on rat and mouse models of diseases or injuries on four radiology systems, tomosynthesis, computed tomography (CT), positron emission tomography/computed tomography (PET-CT), and Magnetic Resonance Imaging (MRI), based on the availability at the author’s institute. Results. Tomosysthesis delineated soft tissue anatomy and hard tissue structure with superb contrast and spatial resolution at minimal scan time and effort. CT allowed high resolution volumetric visualization of bones. Molecular imaging with PET was useful for detecting cancerous tissue in mouse but at the expense of poor resolution. MRI depicted abnormal or intervened tissue at quality and resolution sufficient for experimental studies. The paper discussed limitations of the clinical systems in preclinical imaging as well as challenges regarding the need of additional gadgets, modifications, or upgrades required for longitudinally scanning animals under anesthesia while monitoring their vital signs. Conclusion. Clinical imaging technologies can potentially make cost-effective and efficient contributions to preclinical efforts in obtaining anatomical, structural, and functional information from the underlying tissue while minimally compromising the data quality in certain situations. Mehmet Bilgen Copyright © 2013 Mehmet Bilgen. All rights reserved. -NOTA-CHSg and -CHSg Labeled Microspheres for Lung Perfusion and Liver Radiomicrospheres Therapy Planning Mon, 30 Dec 2013 14:14:35 +0000 http://www.hindawi.com/journals/ijmi/2013/279872/ Fast biodegradable (12 h < half-life < 48 h) radioactive labeled microspheres are needed for PET and SPECT lung perfusion and radiomicrosphere therapy planning. An emulsion method was used to create 30.1 ±4.8 μm size range microspheres with biodegradable Chitosan glycol (CHSg). Microspheres were characterized and labeled with or as an alternative to MAA in perfusion PET and SPECT studies. Surface decoration of CHSg microspheres with p-SCN-Bn-NOTA was performed to increase   in vivo stability. was labeled directly to the CHSg microspheres. Labeling yield and in vitro radiochemical stability were evaluated. In vitro CHSg microsphere degradation half-life was ~24 hours in porcine blood. Labeled microspheres were injected into Sprague Dawley rats and biodistribution was determined after 2 and 4 hours. Both -CHSg and -NOTA-CHSg were quickly allocated in the lungs after injection. -CHSg showed 91.6 ± 6.5% and 83.2 ± 4.1% of the decay corrected injected activity remaining in the lungs after 2 and 4 hours, respectively. For the obtained -NOTA-CHSg microspheres, lung allocation was very high with 98.9 ± 0.2% and 95.6 ± 0.9% after 2 and 4 hours, respectively. The addition of p-SCN-Bn-NOTA acts as a radioprotectant eliminating the released activity from the lungs to the bladder protecting the other organs. Alejandro Amor-Coarasa, Andrew Milera, Denny Carvajal, Seza Gulec, Jared Leichner, and Anthony J. McGoron Copyright © 2013 Alejandro Amor-Coarasa et al. All rights reserved. What Is the Clinical Significance of FDG Unexpected Uptake in the Prostate in Patients Undergoing PET/CT for Other Malignancies? Sat, 28 Dec 2013 11:08:22 +0000 http://www.hindawi.com/journals/ijmi/2013/476786/ Purpose. To determine the clinical significance of unexpected, abnormal FDG uptake in the prostate in patients undergoing FDG-PET/CT for staging of other primary malignancies without a prior history of prostate carcinoma. Methods. Retrospective search of FDG-PET/CT studies to identify patients with unexpected, abnormal FDG uptake in the prostate gland, who underwent subsequent biopsy, was performed. 26 patients were identified. Images were reviewed to determine the pattern of uptake within the prostate (focal or diffuse) and maximum standardized uptake value (SUVmax). PSA and Gleason scores were recorded. Results. 15/26 (58%) patients were found to have prostate carcinoma. Gleason scores ranged from 6 to 9.9. There was no statistical difference in the pattern of uptake (focal versus diffuse) or the SUVmax. Serum PSA levels with cancer (range, 2–26.8 ng; mean, 10.2 ng) and those without cancer (range, 2–10.5 ng; mean, 2.2 ng) were statistically significant (, Wilcoxon rank sum test). Conclusions. Patients with abnormal uptake in the prostate have a 58% likelihood of occult prostate cancer. In the setting of elevated serum PSA levels, abnormal prostate uptake should therefore be viewed with suspicion and a urology consult should be obtained; however, it is irrelevant in patients with underlying aggressive malignancies. Priya Bhosale, Aparna Balachandran, Raghu Vikram, Chitra Viswanathan, Homer Macapinlac, Eric Rohren, and Ramanujan Prativadi Copyright © 2013 Priya Bhosale et al. All rights reserved. Region-Based Partial Volume Correction Techniques for PET Imaging: Sinogram Implementation and Robustness Tue, 17 Dec 2013 10:35:19 +0000 http://www.hindawi.com/journals/ijmi/2013/435959/ Background/Purpose. Limited spatial resolution of positron emission tomography (PET) requires partial volume correction (PVC). Region-based PVC methods are based on geometric transfer matrix implemented either in image-space (GTM) or sinogram-space (GTMo), both with similar performance. Although GTMo is slower, it more closely simulates the 3D PET image acquisition, accounts for local variations of point spread function, and can be implemented for iterative reconstructions. A recent image-based symmetric GTM (sGTM) has shown improvement in noise characteristics and robustness to misregistration over GTM. This study implements the sGTM method in sinogram space (sGTMo), validates it, and evaluates its performance. Methods. Two 3D sphere and brain digital phantoms and a physical sphere phantom were used. All four region-based PVC methods (GTM, GTMo, sGTM, and sGTMo) were implemented and their performance was evaluated. Results. All four PVC methods had similar accuracies. Both noise propagation and robustness of the sGTMo method were similar to those of sGTM method while they were better than those of GTMo method especially for smaller objects. Conclusion. The sGTMo was implemented and validated. The performance of the sGTMo in terms of noise characteristics and robustness to misregistration is similar to that of the sGTM method and improved compared to the GTMo method. Mike Sattarivand, Jennifer Armstrong, Gregory M. Szilagyi, Maggie Kusano, Ian Poon, and Curtis Caldwell Copyright © 2013 Mike Sattarivand et al. All rights reserved. Cholinergic Depletion in Alzheimer’s Disease Shown by [18F]FEOBV Autoradiography Sun, 10 Nov 2013 09:35:13 +0000 http://www.hindawi.com/journals/ijmi/2013/205045/ Rationale. Alzheimer’s Disease (AD) is a neurodegenerative condition characterized in part by deficits in cholinergic basalocortical and septohippocampal pathways. [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV), a Positron Emission Tomography ligand for the vesicular acetylcholine transporter (VAChT), is a potential molecular agent to investigate brain diseases associated with presynaptic cholinergic losses. Purpose. To demonstrate this potential, we carried out an [18F]FEOBV autoradiography study to compare postmortem brain tissues from AD patients to those of age-matched controls. Methods. [18F]FEOBV autoradiography binding, defined as the ratio between regional grey and white matter, was estimated in the hippocampus (13 controls, 8 AD) and prefrontal cortex (13 controls, 11 AD). Results. [18F]FEOBV binding was decreased by 33% in prefrontal cortex, 25% in CA3, and 20% in CA1. No changes were detected in the dentate gyrus of the hippocampus, possibly because of sprouting or upregulation toward the resilient glutamatergic neurons of the dentate gyrus. Conclusion. This is the first demonstration of [18F]FEOBV focal binding changes in cholinergic projections to the cortex and hippocampus in AD. Such cholinergic synaptic (and more specifically VAChT) alterations, in line with the selective basalocortical and septohippocampal cholinergic losses documented in AD, indicate that [18F]FEOBV is indeed a promising ligand to explore cholinergic abnormalities in vivo. Maxime J. Parent, Marc-Andre Bedard, Arturo Aliaga, Luciano Minuzzi, Naguib Mechawar, Jean-Paul Soucy, Esther Schirrmacher, Alexey Kostikov, Serge G. Gauthier, and Pedro Rosa-Neto Copyright © 2013 Maxime J. Parent et al. All rights reserved. The Influence of Hypoxia and pH on Bioluminescence Imaging of Luciferase-Transfected Tumor Cells and Xenografts Sun, 07 Jul 2013 13:18:41 +0000 http://www.hindawi.com/journals/ijmi/2013/287697/ Bioluminescence imaging (BLI) is a relatively new noninvasive technology used for quantitative assessment of tumor growth and therapeutic effect in living animal models. BLI involves the generation of light by luciferase-expressing cells following administration of the substrate luciferin in the presence of oxygen and ATP. In the present study, the effects of hypoxia, hypoperfusion, and pH on BLI signal (BLS) intensity were evaluated in vitro using cultured cells and in vivo using a xenograft model in nude mice. The intensity of the BLS was significantly reduced in the presence of acute and chronic hypoxia. Changes in cell density, viability, and pH also affected BLS. Although BLI is a convenient non-invasive tool for tumor assessment, these factors should be considered when interpreting BLS intensity, especially in solid tumors that could be hypoxic due to rapid growth, inadequate blood supply, and/or treatment. Ashraf A. Khalil, Mark J. Jameson, William C. Broaddus, Peck Sun Lin, Seth M. Dever, Sarah E. Golding, Elizabeth Rosenberg, Kristoffer Valerie, and Theodore D. Chung Copyright © 2013 Ashraf A. Khalil et al. All rights reserved. Evaluation of Nonradiative Clinical Imaging Techniques for the Longitudinal Assessment of Tumour Growth in Murine CT26 Colon Carcinoma Tue, 02 Jul 2013 08:59:28 +0000 http://www.hindawi.com/journals/ijmi/2013/983534/ Background and Objectives. To determine the most appropriate technique for tumour followup in experimental therapeutics, we compared ultrasound (US) and magnetic resonance imaging (MRI) to characterize ectopic and orthotopic colon carcinoma models. Methods. CT26 tumours were implanted subcutaneously (s.c.) in Balb/c mice for the ectopic model or into the caecum for the orthotopic model. Tumours were evaluated by histology, spectrofluorescence, MRI, and US. Results. Histology of CT26 tumour showed homogeneously dispersed cancer cells and blood vessels. The visualization of the vascular network using labelled albumin showed that CT26 tumours were highly vascularized and disorganized. MRI allowed high-resolution and accurate 3D tumour measurements and provided additional anatomical and functional information. Noninvasive US imaging allowed good delineation of tumours despite an hypoechogenic signal. Monitoring of tumour growth with US could be accomplished as early as 5 days after implantation with a shorter acquisition time (<5 min) compared to MRI. Conclusion. MRI and US afforded excellent noninvasive imaging techniques to accurately follow tumour growth of ectopic and orthotopic CT26 tumours. These two techniques can be appropriately used for tumour treatment followup, with a preference for US imaging, due to its short acquisition time and simplicity of use. Johanne Seguin, Bich-Thuy Doan, Heldmuth Latorre Ossa, Lauriane Jugé, Jean-Luc Gennisson, Mickaël Tanter, Daniel Scherman, Guy G. Chabot, and Nathalie Mignet Copyright © 2013 Johanne Seguin et al. All rights reserved. Synthesis of Clinical-Grade [18F]-Fluoroestradiol as a Surrogate PET Biomarker for the Evaluation of Estrogen Receptor-Targeting Therapeutic Drug Thu, 09 May 2013 11:57:31 +0000 http://www.hindawi.com/journals/ijmi/2013/278607/ 16α-[18F]-fluoroestradiol ([18F]FES), a steroid-based positron emission tomography (PET) tracer, has emerged as a dependable tracer for the evaluation and management of estrogen receptor-positive (ER+) breast cancer patients. We have developed a fully automatic, one-pot procedure for the synthesis of [18F]FES using the Eckert & Ziegler (E & Z) radiomodular system. After [18F]fluorination, the intermediate was hydrolyzed with 2.0 M HCl twice and neutralized with sodium bicarbonate. After high-performance liquid chromatography (HPLC) purification, the decay-corrected radiochemical yield and purity of [18F]FES were 40 ± 5.0% () and >97%, respectively. The product was stable up to 10 h. Total synthesis time including HPLC purification was 80 min. This new, fully automated rapid synthetic procedure provided high and reproducible yields of [18F]FES. Quality control (QC) tests showed that the [18F]FES produced by this method met all specifications for human injection. Manish Dixit, Jianfeng Shi, Ling Wei, George Afari, and Sibaprasad Bhattacharyya Copyright © 2013 Manish Dixit et al. All rights reserved. Rhenium-188 Production in Hospitals, by W-188/Re-188 Generator, for Easy Use in Radionuclide Therapy Tue, 09 Apr 2013 09:39:45 +0000 http://www.hindawi.com/journals/ijmi/2013/290750/ Rhenium-188 (Re-188) is a high energy -emitting radioisotope obtained from the tungsten-188/rhenium-188 (W-188/Re-188) generator, which has shown utility for a variety of therapeutic applications in nuclear medicine, oncology, and interventional radiology/cardiology. Re-188 decay is accompanied by a 155 keV predominant energy -emission, which could be detected by -cameras, for imaging, biodistribution, or absorbed radiation dose studies. Its attractive physical properties and its potential low cost associated with a long-lived parent make it an interesting option for clinical use. The setup and daily use of W-188/Re-188 generator in hospital nuclear medicine departments are discussed in detail. The clinical efficacy, for several therapeutic applications, of a variety of Re-188-labeled agents is demonstrated. The high energy of the -emission of Re-188 is particularly well suited for effective penetration in solid tumours. Its total radiation dose delivered to tissues is comparable to other radionuclides used in therapy. Furthermore, radiation safety and shielding requirements are an important subject of matter. In the case of bone metastases treatment, therapeutic ratios are presented in order to describe the efficacy of Re-188 usage. Maria Argyrou, Alexia Valassi, Maria Andreou, and Maria Lyra Copyright © 2013 Maria Argyrou et al. All rights reserved. Effects of ROI Placement on PET-Based Assessment of Tumor Response to Therapy Thu, 07 Mar 2013 07:46:01 +0000 http://www.hindawi.com/journals/ijmi/2013/132804/ Purpose. Quantitative PET response assessment during therapy requires regions of interest (ROI). Commonly, a fixed-size ROI is placed at the maximum uptake point in the pretreatment study. For intratreatment, the ROI is placed either at the maximum uptake point (ROIpeak) or at the same location as the pretreatment ROI (ROIsame). We have evaluated the effects of the ROI placement on response assessment. Methods. PET scans of 15 head and neck cancer patients were used to evaluate the effects of the two ROI methods on response assessment. Results. The average intratreatment ROIpeak uptake was 13.4% higher than the ROIsame uptake (range −14% to 38%). The average relative change in ROIpeak uptake was 7.9% lower than ROIsame uptake (range −5% to 36%), resulting in ambiguous tumour classification in 19% of the tumours. Conclusion. Quantitative PET response assessment using a fixed-size ROI is sensitive the ROI placement. The difference between ROIpeak and ROIsame could be substantial resulting in ambiguous response assessment. Although the fixed-size ROI is simple to implement, it is also prone to the limitations and should be used with caution. Clinical trial data are necessary to establish reliable thresholds for fixed-size ROI techniques and to evaluate their efficacy for response assessment. Mike Sattarivand, Curtis Caldwell, Ian Poon, Hany Soliman, and Katherine Mah Copyright © 2013 Mike Sattarivand et al. All rights reserved. Automatic Segmentation of Lung Carcinoma Using 3D Texture Features in 18-FDG PET/CT Tue, 26 Feb 2013 08:42:57 +0000 http://www.hindawi.com/journals/ijmi/2013/980769/ Target definition is the largest source of geometric uncertainty in radiation therapy. This is partly due to a lack of contrast between tumor and healthy soft tissue for computed tomography (CT) and due to blurriness, lower spatial resolution, and lack of a truly quantitative unit for positron emission tomography (PET). First-, second-, and higher-order statistics, Tamura, and structural features were characterized for PET and CT images of lung carcinoma and organs of the thorax. A combined decision tree (DT) with K-nearest neighbours (KNN) classifiers as nodes containing combinations of 3 features were trained and used for segmentation of the gross tumor volume. This approach was validated for 31 patients from two separate institutions and scanners. The results were compared with thresholding approaches, the fuzzy clustering method, the 3-level fuzzy locally adaptive Bayesian algorithm, the multivalued level set algorithm, and a single KNN using Hounsfield units and standard uptake value. The results showed the DTKNN classifier had the highest sensitivity of 73.9%, second highest average Dice coefficient of 0.607, and a specificity of 99.2% for classifying voxels when using a probabilistic ground truth provided by simultaneous truth and performance level estimation using contours drawn by 3 trained physicians. Daniel Markel, Curtis Caldwell, Hamideh Alasti, Hany Soliman, Yee Ung, Justin Lee, and Alexander Sun Copyright © 2013 Daniel Markel et al. All rights reserved. Comparison of Five Parathyroid Scintigraphic Protocols Mon, 21 Jan 2013 15:54:41 +0000 http://www.hindawi.com/journals/ijmi/2013/921260/ Objectives. We compared five parathyroid scintigraphy protocols in patients with primary (pHPT) and secondary hyperparathyroidism (sHPT) and studied the interobserver agreement. The dual-tracer method (c-sestamibi/123I) was used with three acquisition techniques (parallel-hole planar, pinhole planar, and SPECT/CT). The single-tracer method (c-sestamibi) was used with two acquisition techniques (double-phase parallel-hole planar, and SPECT/CT). Thus five protocols were used, resulting in five sets of images. Materials and Methods. Image sets of 51 patients were retrospectively graded by four experienced nuclear medicine physicians. The final study group consisted of 24 patients (21 pHPT, 3 sHPT) who had been operated upon. Surgical and histopathologic findings were used as the standard of comparison. Results. Thirty abnormal parathyroid glands were found in 24 patients. The sensitivities of the dual-tracer method (76.7–80.0%) were similar (). The sensitivities of the single-tracer method (13.3–31.6%) were similar (). All differences in sensitivity between these two methods were statistically significant (). The interobserver agreement was good. Conclusion. This study indicates that any dual-tracer protocol with c-sestamibi and 123I is superior for enlarged parathyroid gland localization when compared with single-tracer protocols using c-sestamibi alone. The parathyroid scintigraphy was found to be independent of the reporter. Virpi Tunninen, Pekka Varjo, Jukka Schildt, Aapo Ahonen, Tomi Kauppinen, Irina Lisinen, Anu Holm, Hannu Eskola, and Marko Seppänen Copyright © 2013 Virpi Tunninen et al. All rights reserved. In Vivo Tracking of Murine Adipose Tissue-Derived Multipotent Adult Stem Cells and Ex Vivo Cross-Validation Thu, 17 Jan 2013 14:41:30 +0000 http://www.hindawi.com/journals/ijmi/2013/426961/ Stem cells are characterized by the ability to renew themselves and to differentiate into specialized cell types, while stem cell therapy is believed to treat a number of different human diseases through either cell regeneration or paracrine effects. Herein, an in vivo and ex vivo near infrared time domain (NIR TD) optical imaging study was undertaken to evaluate the migratory ability of murine adipose tissue-derived multipotent adult stem cells [mAT-MASC] after intramuscular injection in mice. In vivo NIR TD optical imaging data analysis showed a migration of DiD-labelled mAT-MASC in the leg opposite the injection site, which was confirmed by a fibered confocal microendoscopy system. Ex vivo NIR TD optical imaging results showed a systemic distribution of labelled cells. Considering a potential microenvironmental contamination, a cross-validation study by multimodality approaches was followed: mAT-MASC were isolated from male mice expressing constitutively eGFP, which was detectable using techniques of immunofluorescence and qPCR. Y-chromosome positive cells, injected into wild-type female recipients, were detected by FISH. Cross-validation confirmed the data obtained by in vivo/ex vivo TD optical imaging analysis. In summary, our data demonstrates the usefulness of NIR TD optical imaging in tracking delivered cells, giving insights into the migratory properties of the injected cells. Chiara Garrovo, Natascha Bergamin, Dave Bates, Daniela Cesselli, Antonio Paolo Beltrami, Andrea Lorenzon, Roberto Ferrari, Carlo Alberto Beltrami, Vito Lorusso, and Stefania Biffi Copyright © 2013 Chiara Garrovo et al. All rights reserved. A Rationale for the Use of F18-FDG PET/CT in Fever and Inflammation of Unknown Origin Mon, 17 Dec 2012 11:52:26 +0000 http://www.hindawi.com/journals/ijmi/2012/165080/ This review focuses on the diagnostic value of hybrid F18-FDG Positron Emission Tomography/Computerized tomography (PET/CT) in fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Due to the wide range of possible causes both FUO and IUO remain a clinical challenge for both patients and physicians. In addition, the aetiology of IUO shows the same variation in diseases as the FUO spectrum and probably requires the same diagnostic approach as FUO. There are numerous historically used diagnostic approaches incorporating invasive and non-invasive, and imaging techniques, all with relative high specificity but limited sensitivity. This hampers the generalization of these diagnostic approaches. However, recently published reports show that F18-FDG PET/CT in FUO and IUO has a high sensitivity and a relative non-specificity for malignancy, infection and inflammation. This makes F18-FDG PET/CT an ideal diagnostic tool to start the diagnostic process and to guide subsequent focused diagnostic approaches with higher specificity. In addition, F18-FDG PET/CT has a relative high negative predictive value. Therefore F18 FDG PET/CT should be incorporated in the routine diagnostic work-up of patients with FUO and IUO, preferably at an early stage in the diagnostic process. H. Balink, H. J. Verberne, R. J. Bennink, and B. L. F. van Eck-Smit Copyright © 2012 H. Balink et al. All rights reserved. Optimisation of Simultaneous Tl-201/Tc-99m Dual Isotope Reconstruction with Monte-Carlo-Based Scatter Correction Mon, 19 Nov 2012 09:23:21 +0000 http://www.hindawi.com/journals/ijmi/2012/695632/ Simultaneous Tl-201/Tc-99m dual isotope myocardial perfusion SPECT is seriously hampered by down-scatter from Tc-99m into the Tl-201 energy window. This paper presents and optimises the ordered-subsets-expectation-maximisation-(OS-EM-) based reconstruction algorithm, which corrects the down-scatter using an efficient Monte Carlo (MC) simulator. The algorithm starts by first reconstructing the Tc-99m image with attenuation, collimator response, and MC-based scatter correction. The reconstructed Tc-99m image is then used as an input for an efficient MC-based down-scatter simulation of Tc-99m photons into the Tl-201 window. This down-scatter estimate is finally used in the Tl-201 reconstruction to correct the crosstalk between the two isotopes. The mathematical 4D NCAT phantom and physical cardiac phantoms were used to optimise the number of OS-EM iterations where the scatter estimate is updated and the number of MC simulated photons. The results showed that two scatter update iterations and 105 simulated photons are enough for the Tc-99m and Tl-201 reconstructions, whereas 106 simulated photons are needed to generate good quality down-scatter estimates. With these parameters, the entire Tl-201/Tc-99m dual isotope reconstruction can be accomplished in less than 3 minutes. Tuija Kangasmaa, Jyrki Kuikka, and Antti Sohlberg Copyright © 2012 Tuija Kangasmaa et al. All rights reserved. Contribution of 18F-Fluoro-ethyl-tyrosine Positron Emission Tomography to Target Volume Delineation in Stereotactic Radiotherapy of Malignant Cranial Base Tumours: First Clinical Experience Mon, 12 Nov 2012 13:40:42 +0000 http://www.hindawi.com/journals/ijmi/2012/412585/ Increased amino acid uptake has been demonstrated in intracerebral tumours and head and neck carcinomas of squamous cell origin. We investigated the potential impact of using 18F-fluoro-ethyl-tyrosine (18F-FET)-PET/CT in addition to conventional imaging for gross tumour volume (GTV) delineation in stereotactic radiotherapy of skull base tumours. The study population consisted of 14 consecutive patients with cranial base tumours (10 with squamous cell histology, 4 others). All patients underwent a FET-PET/CT examination in addition to contrast-enhanced CT and 11 patients underwent MRI. All tumours and histologic types showed increased FET uptake. The GTV was defined by all voxels showing hyperintensity in MRI or CT (GTVMRI/CT) or enhancement in PET (GTVPET), forming a GTVcomposite that was used for the initial treatment fields. An additional volume of infiltrative growth outside the GTVMRI/CT of about 1.0 ± 2 cm3 (5% of the conventional volume) was demonstrated by FET-PET only (GTVPETplus) with significant enlargement (>10% of GTVMRI/CT) in three patients. From existing data, we found correlation between cellular density and the standardized uptake value (SUV) of FET. We were able to substantially reduce the volume of escalated radiation dose (GTVboost) by 11 ± 2 cm3 (24%) of the conventional volume. Reinhold Graf, Michail Plotkin, Fonyuy Nyuyki, Peter Wust, Reinhard Wurm, Volker Budach, Winfried Brenner, and Daniel Fahdt Copyright © 2012 Reinhold Graf et al. All rights reserved. Differential Short-Term Repeated Forearm Hyperaemic Reactivity in Coronary Artery Disease Patients Compared to Healthy Low Risk Participants Mon, 12 Nov 2012 11:32:06 +0000 http://www.hindawi.com/journals/ijmi/2012/578504/ The hyperaemic response of the forearm is a widely used technique to assess the vascular reactivity. Little is known about the short-term reproducibility and the possible exhaustion of this response in normal or diseased states. As such, the current study was conducted to assess this phenomenon using a unique nuclear medicine- (NM-) based technique. 19 patients with coronary artery disease (CAD) undergoing NM exercise stress tests and 15 low risk (LR) participants completed 2 reactive hyperaemia tests, using a SPECT-based technique, separated by 15  min. Analyses revealed that CAD patients had lower hyperaemic responses than LR participants (), and that there was a significant group × time interaction (), such that LR participants showed a larger decrease in the reactivity ( to ) than the CAD patients ( to ). These results suggest that there is a variability, due to disease states, in the reproducibility of the hypaeremic reactivity. This needs to be taken into account in short-term repeated measure studies. Simon L. Bacon, Bernard Meloche, Kim L. Lavoie, and André Arsenault Copyright © 2012 Simon L. Bacon et al. All rights reserved. Engineering Molecular Beacons for Intracellular Imaging Tue, 06 Nov 2012 17:12:01 +0000 http://www.hindawi.com/journals/ijmi/2012/501579/ Molecular beacons (MBs) represent a class of nucleic acid probes with unique DNA hairpin structures that specifically target complementary DNA or RNA. The inherent “OFF” to “ON” signal transduction mechanism of MBs makes them promising molecular probes for real-time imaging of DNA/RNA in living cells. However, conventional MBs have been challenged with such issues as false-positive signals and poor biostability in complex cellular matrices. This paper describes the novel engineering steps used to improve the fluorescence signal and reduce to background fluorescence, as well as the incorporation of unnatural nucleotide bases to increase the resistance of MBs to nuclease degradation for application in such fields as chemical analysis, biotechnology, and clinical medicine. The applications of these de novo MBs for single-cell imaging will be also discussed. Cuichen Sam Wu, Lu Peng, Mingxu You, Da Han, Tao Chen, Kathryn R. Williams, Chaoyong James Yang, and Weihong Tan Copyright © 2012 Cuichen Sam Wu et al. All rights reserved. Quantitative Longitudinal Imaging of Vascular Inflammation and Treatment by Ezetimibe in apoE Mice by FMT Using New Optical Imaging Biomarkers of Cathepsin Activity and Integrin Wed, 17 Oct 2012 13:35:15 +0000 http://www.hindawi.com/journals/ijmi/2012/189254/ Inflammation as a core pathological event of atherosclerotic lesions is associated with the secretion of cathepsin proteases and the expression of integrin. We employed fluorescence molecular tomographic (FMT) noninvasive imaging of these molecular activities using cathepsin sensing (ProSense, CatB FAST) and integrin (IntegriSense) near-infrared fluorescence (NIRF) agents. A statistically significant increase in the ProSense and IntegriSense signal was observed within the chest region of apoE−/− mice () versus C57BL/6 mice starting 25 and 22 weeks on high cholesterol diet, respectively. In a treatment study using ezetimibe (7 mg/kg), there was a statistically significant reduction in the ProSense and CatB FAST chest signal of treated () versus untreated apoE−/− mice at 31 and 21 weeks on high cholesterol diet, respectively. The signal of ProSense and CatB FAST correlated with macrophage counts and was found associated with inflammatory cells by fluorescence microscopy and flow cytometry of cells dissociated from aortas. This report demonstrates that cathepsin and integrin NIRF agents can be used as molecular imaging biomarkers for longitudinal detection of atherosclerosis, and cathepsin agents can monitor anti-inflammatory effects of ezetimibe with applications in preclinical testing of therapeutics and potentially for early diagnosis of atherosclerosis in patients. Shu-An Lin, Manishkumar Patel, Donna Suresch, Brett Connolly, Bagna Bao, Kevin Groves, Milind Rajopadhye, Jeffrey D. Peterson, Michael Klimas, Cyrille Sur, and Bohumil Bednar Copyright © 2012 Shu-An Lin et al. All rights reserved. 64Cu-NODAGA-c(RGDyK) Is a Promising New Angiogenesis PET Tracer: Correlation between Tumor Uptake and Integrin Expression in Human Neuroendocrine Tumor Xenografts Tue, 02 Oct 2012 18:33:24 +0000 http://www.hindawi.com/journals/ijmi/2012/379807/ Purpose. The purpose of this paper is to evaluate a new PET tracer 64Cu-NODAGA-c(RGDyK) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans. Procedures. Nude mice with human neuroendocrine tumor xenografts (H727) were administered 64Cu-NODAGA-c(RGDyK) i.v. for study of biodistribution as well as for dynamic PET. Gene expression of angiogenesis markers integrin , integrin , and VEGF-A were analyzed using QPCR and correlated to the tracer uptake in the tumors (%ID/g). From biodistribution data human radiation-absorbed doses were estimated using OLINDA/EXM. Results. Tumor uptake was 1.2%ID/g with strong correlations between gene expression and tracer uptake, for integrin  , integrin   and VEGF-A (all ). The whole body effective dose for humans was estimated to be 0.038 and 0.029 mSv/MBq for females and males, respectively, with highest absorbed dose in bladder wall. Conclusion. 64Cu-NODAGA-c(RGDyK) is a promising new angiogenesis PET tracer with potential for human use. Jytte Oxboel, Christina Schjoeth-Eskesen, Henrik H. El-Ali, Jacob Madsen, and Andreas Kjaer Copyright © 2012 Jytte Oxboel et al. All rights reserved. 123I-MIBG Scintigraphy as a Powerful Tool to Plan an Implantable Cardioverter Defibrillator and to Assess Cardiac Resynchronization Therapy in Heart Failure Patients Wed, 26 Sep 2012 15:03:15 +0000 http://www.hindawi.com/journals/ijmi/2012/690468/ Iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy is a nuclear medicine technique which describes the functional status of the cardiac sympathetic nervous system. It is well known that an autonomic dysfunction is present in heart failure setting as a neuronal uptake of norepinephrine is impaired in the failing myocardium. Reduction in sympathetic nervous function in the heart, measured by reduced myocardial uptake of 123I-MIBG, is an indicator of poor prognosis for heart failure patients. The aim of this paper was to investigate the role of 123I-MIBG scintigraphy in evaluating the need of implantable cardioverter defibrillator (ICD) and the response to cardiac resynchronization therapy (CRT) in heart failure patients. For this purpose scientific literature data on these topics were reviewed. Based on literature data, 123I-MIBG scintigraphy seems to be a useful tool to assess which patients may benefit most from an ICD implantation to reduce the risk of ventricular arrhythmia or sudden cardiac death. Furthermore, 123I-MIBG scintigraphy seems to predict which patients will response to CRT with an improvement in left ventricular function. Antonella Stefanelli, Giorgio Treglia, and Alessandro Giordano Copyright © 2012 Antonella Stefanelli et al. All rights reserved. Evaluation of Norepinephrine Transporter Expression and Metaiodobenzylguanidine Avidity in Neuroblastoma: A Report from the Children's Oncology Group Tue, 25 Sep 2012 18:44:28 +0000 http://www.hindawi.com/journals/ijmi/2012/250834/ Purpose. 123I-metaiodobenzylguanidine (MIBG) is used for the diagnostic evaluation of neuroblastoma. We evaluated the relationship between norepinephrine transporter (NET) expression and clinical MIBG uptake. Methods. Quantitative reverse transcription PCR (N=82) and immunohistochemistry (IHC; N=61) were performed for neuroblastoma NET mRNA and protein expression and correlated with MIBG avidity on diagnostic scans. The correlation of NET expression with clinical features was also performed. Results. Median NET mRNA expression level for the 19 MIBG avid patients was 12.9% (range 1.6–73.7%) versus 5.9% (range 0.6–110.0%) for the 8 nonavid patients (P=0.31). Median percent NET protein expression was 50% (range 0–100%) in MIBG avid patients compared to 10% (range 0–80%) in nonavid patients (P=0.027). MYCN amplified tumors had lower NET protein expression compared to nonamplified tumors (10% versus 50%; P=0.0002). Conclusions. NET protein expression in neuroblastoma correlates with MIBG avidity. MYCN amplified tumors have lower NET protein expression. Steven G. DuBois, Ethan Geier, Vandana Batra, Sook Wah Yee, John Neuhaus, Mark Segal, Daniel Martinez, Bruce Pawel, Greg Yanik, Arlene Naranjo, Wendy B. London, Susan Kreissman, David Baker, Edward Attiyeh, Michael D. Hogarty, John M. Maris, Kathleen Giacomini, and Katherine K. Matthay Copyright © 2012 Steven G. DuBois et al. All rights reserved. Reproducible Analysis of Rat Brain PET Studies Using an Additional [18F]NaF Scan and an MR-Based ROI Template Sun, 23 Sep 2012 11:40:15 +0000 http://www.hindawi.com/journals/ijmi/2012/580717/ Background. An important step in the analysis of positron emission tomography (PET) studies of the brain is the definition of regions of interest (ROI). Image coregistration, ROI analysis, and quantification of brain PET data in small animals can be observer dependent. The purpose of this study was to investigate the feasibility of ROI analysis based on a standard MR template and an additional [18F]NaF scan. Methods. [18F]NaF scans of 10 Wistar rats were coregistered with a standard MR template by 3 observers and derived transformation matrices were applied to corresponding [11C]AF150(S) images. Uptake measures were derived for several brain regions delineated using the MR template. Overall agreement between the 3 observers was assessed by interclass correlation coefficients (ICC) of uptake data. In addition, [11C]AF150(S) ROI data were compared with ex vivo biodistribution data. Results. For all brain regions, ICC analysis showed excellent agreement between observers. Reproducibility, estimated by calculation of standard deviation of the between-observer differences, was demonstrated by an average of 17% expressed as coefficient of variation. Uptake of [11C]AF150(S) derived from ROI analysis closely matched ex vivo biodistribution data. Conclusions. The proposed method provides a reproducible and tracer-independent method for ROI analysis of rat brain PET data. Hans J. C. Buiter, Floris H. P. van Velden, Josée E. Leysen, Abraham Fisher, Albert D. Windhorst, Adriaan A. Lammertsma, and Marc C. Huisman Copyright © 2012 Hans J. C. Buiter et al. All rights reserved. Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Assessing Retroperitoneal Fibrosis: A Literature Review Thu, 20 Sep 2012 11:44:21 +0000 http://www.hindawi.com/journals/ijmi/2012/484052/ Background and Purpose. Several studies have evaluated the role of fluorine-18-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography (FDG-PET and PET/CT) in diagnosing and assessing disease activity in patients with retroperitoneal fibrosis (RF). The aim of our paper is to perform a literature review on this topic. Methods. Scientific articles that evaluated the usefulness of FDG-PET and PET/CT in patients with RF were searched and discussed. Results. Eleven studies were found, and the main findings of these articles were described. Conclusion. FDG-PET and PET/CT are useful functional imaging methods for assessing patients with RF both in the diagnosis and in the treatment response evaluation. Moreover, further studies are needed to substantiate the role of FDG-PET and PET/CT in patients with RF. Giorgio Treglia, Maria Vittoria Mattoli, and Francesco Bertagna Copyright © 2012 Giorgio Treglia et al. All rights reserved. The Role of Fluorine-18-fluorodeoxyglucose Positron Emission Tomography in Assessing the Response to Neoadjuvant Treatment in Patients with Osteosarcoma Thu, 13 Sep 2012 14:07:26 +0000 http://www.hindawi.com/journals/ijmi/2012/870301/ Aim. The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with fluorine-18-fluorodeoxyglucose (FDG) in assessing the response to neoadjuvant treatment in patients with osteosarcoma (OS). Methods. A comprehensive literature search of published studies through March 2012 in PubMed/MEDLINE, Embase, and Scopus databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was performed. Results. Twenty-two studies have investigated the role of FDG-PET and FDG-PET/CT in the evaluation of response to neoadjuvant treatment with either chemotherapy or radiation therapy in patients with OS. The main findings of these studies are presented. Conclusion. FDG-PET or PET/CT seems to be sensitive and reliable diagnostic tools in the assessment of metabolic response to treatment in patients with OS, after baseline PET evaluation has been performed in advance. However, false positive findings due to inflammation in sites of tumoral response should be considered. Carmelo Caldarella, Marco Salsano, Maria Antonietta Isgrò, and Giorgio Treglia Copyright © 2012 Carmelo Caldarella et al. All rights reserved. The Role of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Evaluating the Response to Treatment in Patients with Multiple Myeloma Fri, 10 Aug 2012 17:41:42 +0000 http://www.hindawi.com/journals/ijmi/2012/175803/ Background and Aim. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is well recognized as a powerful diagnostic tool in the initial staging of patients with multiple myeloma (MM). The aim of this paper is to perform a systematic review about the usefulness of FDG-PET or PET/CT in evaluating the response to treatment in patients with MM. Methods. The scientific literature about the role of FDG-PET or PET/CT in evaluating the response to treatment in patients affected by MM was systematically reviewed. Results. Ten studies about the role of FDG-PET or PET/CT in evaluating treatment response in MM were retrieved and discussed. Conclusions. FDG-PET or PET/CT seems to be helpful in assessing the response to treatment in patients with MM and in the evaluation of possible sites of recurrent or progressive disease. Carmelo Caldarella, Giorgio Treglia, Maria Antonietta Isgrò, Ivan Treglia, and Alessandro Giordano Copyright © 2012 Carmelo Caldarella et al. All rights reserved.