International Journal of Molecular Imaging The latest articles from Hindawi © 2018 , Hindawi Limited . All rights reserved. 99mTc-Sestamibi/123I Subtraction SPECT/CT in Parathyroid Scintigraphy: Is Additional Pinhole Imaging Useful? Wed, 18 Oct 2017 00:00:00 +0000 Objectives. This retrospective study evaluated whether the use of additional anterior -sestamibi/123I pinhole imaging improves the outcome of -sestamibi/123I subtraction SPECT/CT in parathyroid scintigraphy (PS). Materials and Methods. PS using simultaneous dual-isotope subtraction methods and an acquisition protocol combining SPECT/CT and planar pinhole imaging was performed for 175 patients with primary or secondary hyperparathyroidism. All patients who proceeded to surgery with complete postsurgery laboratory findings were included in this study . SPECT/CT images alone and combined with pinhole images were evaluated. Results. There were 111 enlarged parathyroid glands of which 104 and 108 glands were correctly visualized by SPECT/CT (seven false positives) or SPECT/CT with pinhole (three false positives), respectively. Both sensitivity and specificity were higher with combined SPECT/CT with pinhole than with SPECT/CT alone (97% versus 94% and 99% versus 98%, resp., not significant). The false-positive rate was 6% with SPECT/CT and decreased to 3% using combined SPECT/CT with pinhole. Conclusion. -sestamibi/123I subtraction SPECT/CT is a highly sensitive and specific protocol for PS. The use of additional anterior pinhole imaging increases both sensitivity and specificity of PS, although this increase is not statistically significant. Virpi Tunninen, Pekka Varjo, Tomi Kauppinen, Anu Holm, Hannu Eskola, and Marko Seppänen Copyright © 2017 Virpi Tunninen et al. All rights reserved. Visualization of Inflammation at Early Stage of Lung Cancer in Xenografted Temporally Immunosuppression Rats by Ferrioxamine Magnetic Resonance Imaging Thu, 15 Dec 2016 07:03:00 +0000 Physiological responses such as chronic inflammation and angiogenesis could be used as biomarkers for early detection of cancer with noninvasive imaging modalities. The present study reports the application of magnetic resonance imaging instrument to image the binding of ferrioxamine with hemin that allows visualizing the chronic inflammation foci of lung tissue of immunocompromised rats xenografted using small cell lung carcinoma. A low concentration of ferrioxamine (μM·kg−1 of rat weight) deposited on tissue outside the vasculature was found to diffuse across the capillary walls to the interstitial space and inflammation foci, which provided a clear enhancement of T1-weighted gradient-echo sequence images. Ferrioxamine imaging allowed the determination of inflammatory sites and their localization in 3D fat-suppressed maximum intensity projections. The smallest dimension of foci that can be clearly determined is about 0.1 mm3. In concomitant to the in vivo imaging, analysis of histological tissue section showed the development of inflammatory sites. This study provides evidence that medical imaging instrument such as MRI scanner allows researchers to correlate images taken with MRI with those using high-resolution microscopy. Moreover, ferrioxamine is a useful molecular probe for determining chronic inflammation particularly at the very early stages of cancer. Nathupakorn Dechsupa, Chatchanok Udomtanakunchai, Anan Udom-Utraracheva, Dutsadee Suttho, Lionel Pazart, Philippe Humbert, Manuel Garrigos, and Samlee Mankhetkorn Copyright © 2016 Nathupakorn Dechsupa et al. All rights reserved. Understanding Lung Deposition of Alpha-1 Antitrypsin in Acute Experimental Mouse Lung Injury Model Using Fluorescence Microscopy Tue, 06 Dec 2016 12:28:13 +0000 Human plasma-derived α1-antitrypsin (AAT) delivered by intravenous infusion is used as augmentation therapy in patients with emphysema who have a genetic mutation resulting in deficiency of AAT. Inhalation is an alternative route of administration that can potentially increase the efficacy and convenience of treatment. This study was conducted to determine whether delivery to the lungs, initially via the intratracheal (IT) route of administration, would deliver efficacious levels of a recombinant AAT (rAAT) to the site of action in the lungs in mice. 125I-radiolabeled rAAT, fluorophore-conjugated rAAT (rAAT-Alexa488), and NE680 (neutrophil elastase 680, a silent fluorescent substrate of neutrophil elastase which fluoresces in the near-infrared range upon activation by neutrophil elastase) were used to characterize the pharmacokinetics and tissue distribution profile, distribution of rAAT within the lung, and efficacy of rAAT to inhibit neutrophil elastase at the site of action, respectively. The study has demonstrated that rAAT was able to gain access to locations where neutrophil elastase was localized. The histochemical quantification of rAAT activity relative to dose at the site of action provided here will improve confidence in predicting the human dose via the inhalation route. Mengmeng Wang, Yutian Zhan, Jianqing Chen, Haojing Rong, Shawn P. O’Neil, Brahma Ghosh, Vuong Nguyen, Jane Owens, Xianfeng Li, and Denise M. O’Hara Copyright © 2016 Mengmeng Wang et al. All rights reserved. Radium-223 Therapy for Patients with Metastatic Castrate-Resistant Prostate Cancer: An Update on Literature with Case Presentation Tue, 27 Sep 2016 09:47:38 +0000 Background and Purpose. Radium-223 dichloride (Xofigo®, Bayer HealthCare Pharmaceuticals Inc.) is the first α-particle emitter therapeutic agent approved by the FDA, with benefits in overall survival and delay in symptomatic skeletal event for patients with metastatic castrate-resistant prostate cancer (CRPC). Recent post hoc analyses of the phase III ALSYMPCA trial support the previously established safety profile as well as therapeutic effect and clinical outcome of Radium-223. Currently, Radium-223 is approved as a single agent therapy for metastatic CRPC. Clinical trials are currently investigating Radium-223 in additional clinical settings such as earlier asymptomatic disease and in combination with other agents including hormonal therapeutic agents and immunotherapeutic as well as chemotherapeutic agents. Trials are also ongoing in patients with other primary cancers such as breast cancer, thyroid cancer, and renal cancer metastatic to bone. In this article, the physics and radiobiology, as well as a literature update on the use of Radium-223, are provided along with case presentations, aiming at a better appreciation of research data as well as the assimilation of research data into clinical practice. Nghi C. Nguyen, Muhammad Shah, Leonard J. Appleman, Rahul Parikh, and James M. Mountz Copyright © 2016 Nghi C. Nguyen et al. All rights reserved. Accuracy of Hepatobiliary Scintigraphy after Liver Transplantation and Liver Resection Wed, 03 Aug 2016 12:17:14 +0000 Background and Aims. Biliary complications are the most frequent complications after common liver surgeries. In this study, accuracy of hepatobiliary scintigraphy (HBS) and impact of hyperbilirubinemia were evaluated. Methods. Between November 2007 and February 2016, 131 patients underwent hepatobiliary scintigraphy after having liver surgery. 39 patients with 42 scans after LTX () or hepatic resection () were evaluated in the study; 27 were male, with mean age 60 years. The subjects underwent hepatobiliary scintigraphy with Tc-99m labeled Mebrofenin. The results were compared to ERCP as gold standard performed within one month after HBS. We calculated sensitivity, specificity, PPV, and NPV. We compared LTX patients to patients with other liver surgeries. Furthermore the influence of hyperbilirubinemia on HBS scans was evaluated. Results. HBS always provided the correct diagnosis in cases of bile leak in the liver-resected group (14/14). Overall diagnostic accuracy was 76% (19/25) in this group and 54% (7/13) in the LTX group. False negative (FN) diagnoses occurred more often among LTX patients (). Hyperbilirubinemia (>5 mg/dL) significantly influenced the excretion function of the liver, prolonging HBS’s time-activity-curve (). Conclusions. Hepatobiliary scintigraphy is a reliable tool to detect biliary complications, but reduced accuracy must be considered after LTX. Manuel Eckenschwiller, Hanns Ackermann, Wolf O. Bechstein, and Frank Grünwald Copyright © 2016 Manuel Eckenschwiller et al. All rights reserved. A Pilot Study of 18F-FLT PET/CT in Pediatric Lymphoma Thu, 26 May 2016 13:05:22 +0000 We performed an observational pilot study of 18F-FLT PET/CT in pediatric lymphoma. Eight patients with equivocal 18F-FDG PET/CT underwent imaging with 18F-FLT PET/CT. No immediate adverse reactions to 18F-FLT were observed. Compared to 18F-FDG, 18F-FLT uptake was significantly higher in bone marrow and liver (18F-FLT SUV and , versus 18F-FDG SUV and , resp., ). In total, 15 lesions were evaluated with average 18F-FDG and 18F-FLT SUVs of and , respectively. Nonspecific uptake in reactive lymph nodes and thymus was observed. Future studies to assess the clinical utility of 18F-FLT PET/CT in pediatric lymphoma are planned. Danny L. Costantini, Reza Vali, Susan McQuattie, Jeffrey Chan, Angela Punnett, Shiela Weitzman, Amer Shammas, and Martin Charron Copyright © 2016 Danny L. Costantini et al. All rights reserved. Seasonal Temperature Changes Do Not Affect Cardiac Glucose Metabolism Tue, 29 Dec 2015 12:33:35 +0000 FDG-PET/CT is widely used to diagnose cardiac inflammation such as cardiac sarcoidosis. Physiological myocardial FDG uptake often creates a problem when assessing the possible pathological glucose metabolism of the heart. Several factors, such as fasting, blood glucose, and hormone levels, influence normal myocardial glucose metabolism. The effect of outdoor temperature on myocardial FDG uptake has not been reported before. We retrospectively reviewed 29 cancer patients who underwent PET scans in warm summer months and again in cold winter months. We obtained myocardial, liver, and mediastinal standardized uptake values (SUVs) as well as quantitative cardiac heterogeneity and the myocardial FDG uptake pattern. We also compared age and body mass index to other variables. The mean myocardial FDG uptake showed no significant difference between summer and winter months. Average outdoor temperature did not correlate significantly with myocardial SUVmax in either summer or winter. The heterogeneity of myocardial FDG uptake did not differ significantly between seasons. Outdoor temperature seems to have no significant effect on myocardial FDG uptake or heterogeneity. Therefore, warming the patients prior to attending cardiac PET studies in order to reduce physiological myocardial FDG uptake seems to be unnecessary. Jukka Schildt, Antti Loimaala, Eero Hippeläinen, Päivi Nikkinen, and Aapo Ahonen Copyright © 2015 Jukka Schildt et al. All rights reserved. Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging Mon, 28 Sep 2015 06:32:01 +0000 Background. Intraoperative imaging can identify cancer cells in order to improve resection; thus fluorescent contrast agents have emerged. Our objective was to do a preclinical comparison of two fluorescent dyes, EC17 and OTL38, which both target folate receptor but have different fluorochromes. Materials. HeLa and KB cells lines were used for in vitro and in vivo comparisons of EC17 and OTL38 brightness, sensitivity, pharmacokinetics, and biodistribution. In vivo experiments were then performed in mice. Results. The peak excitation and emission wavelengths of EC17 and OTL38 were 470/520 nm and 774/794 nm, respectively. In vitro, OTL38 required increased incubation time compared to EC17 for maximum fluorescence; however, peak signal-to-background ratio (SBR) was 1.4-fold higher compared to EC17 within 60 minutes (). Additionally, the SBR for detecting smaller quantity of cells was improved with OTL38. In vivo, the mean improvement in SBR of tumors visualized using OTL38 compared to EC17 was 3.3 fold (range 1.48–5.43). Neither dye caused noticeable toxicity in animal studies. Conclusions. In preclinical testing, OTL38 appears to have superior sensitivity and brightness compared to EC17. This coincides with the accepted belief that near infrared (NIR) dyes tend to have less autofluorescence and scattering issues than visible wavelength fluorochromes. Elizabeth De Jesus, Jane J. Keating, Sumith A. Kularatne, Jack Jiang, Ryan Judy, Jarrod Predina, Shuming Nie, Philip Low, and Sunil Singhal Copyright © 2015 Elizabeth De Jesus et al. All rights reserved. Feasibility and Initial Performance of Simultaneous SPECT-CT Imaging Using a Commercial Multi-Modality Preclinical Imaging System Wed, 03 Jun 2015 12:06:31 +0000 Multi-modality imaging provides coregistered PET-CT and SPECT-CT images; however such multi-modality workflows usually consist of sequential scans from the individual imaging components for each modality. This typical workflow may result in long scan times limiting throughput of the imaging system. Conversely, acquiring multi-modality data simultaneously may improve correlation and registration of images, improve temporal alignment of the acquired data, increase imaging throughput, and benefit the scanned subject by minimizing time under anesthetic. In this work, we demonstrate the feasibility and procedure for modifying a commercially available preclinical SPECT-CT platform to enable simultaneous SPECT-CT acquisition. We also evaluate the performance of simultaneous SPECT-CT tomographic imaging with this modified system. Performance was accessed using a 57Co source and image quality was evaluated with phantoms in a series of simultaneous SPECT-CT scans. Dustin R. Osborne and Derek W. Austin Copyright © 2015 Dustin R. Osborne and Derek W. Austin. All rights reserved. Nanoparticle Enhanced MRI Scanning to Detect Cellular Inflammation in Experimental Chronic Renal Allograft Rejection Tue, 14 Apr 2015 11:16:17 +0000 Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO-) enhanced magnetic resonance imaging (MRI) can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using -weighted protocols. values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36) versus 0.96 (0.92 to 1.04), ). values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51)) compared to native kidney (2.91 (1.11 to 6.46) ). Increased signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage. S. R. Alam, G. H. Tse, C. Stirrat, T. J. MacGillivray, R. J. Lennen, M. A. Jansen, D. E. Newby, L. Marson, and P. A. Henriksen Copyright © 2015 S. R. Alam et al. All rights reserved. 99mTechnetium Sestamibi-123Iodine Scintigraphy Is More Accurate Than 99mTechnetium Sestamibi Alone before Surgery for Primary Hyperparathyroidism Sun, 01 Feb 2015 06:59:11 +0000 Objectives. Studies comparing outcome of single-c-methoxyisobutylisonitrile (c-sestamibi) and dual-tracer c-sestamibi scintigraphy in combination with 123I before primary surgery of primary hyperparathyroidism (PHPT) are scarce. Methods. We compared c-sestamibi/123I and c-sestamibi in a single-centre retrospective series of 269 PHPT patients. The results were related to laboratory, surgical and histological findings. Results. c-sestamibi/123I and c-sestamibi were positive in 206 (76.6%) and 111 (41.3%) of 269 patients, respectively (P < 0.001). Accuracies for c-sestamibi/123I and c-sestamibi were 63.4% and 34.9%, respectively (96% CI, P < 0.001). Prevalence of multiglandular disease was 15.2%. In multiglandular disease, c-sestamibi/123I and c-sestamibi revealed 43.8 and 22.1% of pathological glands, respectively (P < 0.001). Cure rate was similar for patients with (191/206; 92.7%) and without (59 of 63; 93.7%) a positive c-sestamibi/123I finding. Duration of targeted surgery (one or two quadrants) was 21 and 15 minutes shorter than bilateral neck exploration, respectively (both P < 0.001). Higher serum calcium (P = 0.014) and PTH (P = 0.055) concentrations and larger tumours (P < 0.001) characterized the 206 patients with a positive preoperative scan who were cured by removal of a single adenoma. Conclusions. c-sestamibi/123I scintigraphy is more accurate than c-sestamibi before surgery of PHPT. However, outcome of surgery is not determined by scintigraphy alone. Eeva M. Ryhänen, Jukka Schildt, Ilkka Heiskanen, Mika Väisänen, Aapo Ahonen, Eliisa Löyttyniemi, Camilla Schalin-Jäntti, and Matti J. Välimäki Copyright © 2015 Eeva M. Ryhänen et al. All rights reserved. Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a Potential Agonist Ligand for SPECT Imaging of Dopamine D2/3 Receptors Thu, 25 Dec 2014 07:19:56 +0000 For imaging of dopamine D2/3 receptors, agonist tracers are favoured over antagonists because they are more sensitive to detection of dopamine release and because they may selectively label the high-affinity receptor state. We have developed novel D2/3 receptor selective agonists that can be radiolabelled with [123I], which label is advantageous over most other labels, such as carbon-11, as it has a longer half-life. Particularly, we considered (R) N-[7-hydroxychroman-2-yl]-methyl 4-iodobenzyl amine (compound 1) as an attractive candidate for development as it shows high binding affinity to D2/3 receptors in vitro, and here we report on the characterization of this first [123I]-labelled D2/3 receptor agonist radiopharmaceutical intended for SPECT imaging. The appropriate tin precursor for [123I]-1 was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30–35%) and a good purity (>95%) for [123I]-1. In biodistribution experiments in Wistar rats intravenous injection of [123I]-1 resulted in a fast brain uptake, where the observed binding in the D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30 min to 4 h p.i. Storage phosphor imaging experiments, however, did not show specific D2/3 receptor binding. In conclusion, despite promising in vitro data for 1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [123I]-1. Jan-Peter van Wieringen, Kora de Bruin, Henk M. Janssen, P. Michel Fransen, Anton G. M. Janssen, Peter A. van Doremalen, Martin C. Michel, Philip H. Elsinga, and Jan Booij Copyright © 2014 Jan-Peter van Wieringen et al. 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 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 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 -anti-RAGE , 3 with -nonimmune IgG , and all with CT contrast agent and underwent SPECT/CT imaging. At necropsy, the proximal aorta was weighed, counted, and sectioned and the % injected dose per gram (%ID/g) was calculated. From the merged SPECT/CT scans, tracer uptake localized to arteries was lower in the treated mice: versus %ID (). Percent cross-sectional lesion area was smaller in the treated (% versus %) (). RAGE uptake on scans (%ID) correlated with quantitative RAGE staining in the atheroma and with %ID/g (; ). Lesion size as percent cross-sectional area was smaller in the treated (% versus %) (). RAGE uptake on scans (%ID) correlated with quantitative RAGE staining in the atheroma and with %ID/g (; ). 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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.