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A Validation Study of Automated Bone Scan Index: Effect on Reproducibility Due to the Procedural Variability in Bone Scan Image Acquisition. A Common Mistake.
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A Validation Study of Automated Bone Scan Index: Effect on Reproducibility Due to the Procedural Variability in Bone Scan Image Acquisition. A Common Mistake.

J Nucl Med. 2017 Jan 12;:

Authors: Sabour S

PMID: 28082440 [PubMed - as supplied by publisher]




Dissociation between brown adipose tissue 18F-FDG uptake and thermogenesis in uncoupling protein 1 deficient mice.
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Dissociation between brown adipose tissue 18F-FDG uptake and thermogenesis in uncoupling protein 1 deficient mice.

J Nucl Med. 2017 Jan 12;:

Authors: Hankir MK, Kranz M, Keipert S, Weiner J, Andreasen SG, Kern M, Patt M, Klöting N, Heiker JT, Hesse S, Brust P, Jastroch M, Fenske W

Abstract
(18)F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain whether BAT (18)F-FDG uptake reliably tracks UCP1-mediated heat production.
METHODS: UCP1 knockout (UCP1 KO) and wild-type mice received the selective β3 adrenergic receptor agonist CL 316, 243 (1mg/kg) and underwent metabolic cage, infrared thermal imaging and (18)F-FDG PET/magnetic resonance imaging (MRI) experiments. Primary brown adipocytes were additionally examined for their bioenergetics as well as their uptake of 2-deoxy-3H-glucose.
RESULTS: In response to CL 316, 243 treatments, oxygen consumption and BAT thermogenesis were diminished in UCP1 KO mice but BAT (18)F-FDG uptake was fully retained. UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy-3H-glucose uptake rates were largely unaffected.
CONCLUSION: Increased BAT (18)F-FDG uptake can occur independently of UCP1 function.

PMID: 28082439 [PubMed - as supplied by publisher]




The impact of SSTR-directed PET/CT on the management of patients with neuroendocrine tumor: A systematic review and meta-analysis.
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The impact of SSTR-directed PET/CT on the management of patients with neuroendocrine tumor: A systematic review and meta-analysis.

J Nucl Med. 2017 Jan 12;:

Authors: Barrio M, Czernin J, Fanti S, Ambrosini V, Binse I, Du L, Eiber M, Herrmann K, Fendler WP

Abstract
INTRODUCTION: Somatostatin receptor (SSTR) imaging is widely used for guiding the management of neuroendocrine tumor (NET) patients. (68)Ga-DOTATATE approval by the US Food and Drug Administration has triggered widespread clinical interest in SSTR Positron Emission Tomography/Computed Tomography (PET/CT) throughout the US. Here we performed a systematic review and meta-analysis to evaluate the impact of SSTR PET/CT on the management of patients with NETs.
METHODS: A comprehensive literature search was performed using The National Center for Biotechnology Information PubMed online database applying the following keywords: "management" AND "PET" AND "neuroendocrine". Fourteen of 190 studies were deemed suitable based on the following inclusion criteria: original research, cohort study, number of patients ≥ 10, reported change in management after SSTR PET/CT. Change in management across studies was determined by a random effects model.
RESULTS: A total of 1,561 patients were included. Overall, change in management occurred in 44% (range: 16-71%) of NET patients after SSTR PET/CT. In 4/14 studies SSTR PET/CT was performed after an (111)In-Octreotide scan. In this subgroup additional information by SSTR PET/CT led to a change in management in 39% (range: 16-71%) of patients. Seven/14 studies differentiated between inter- and intra-modality changes with the majority of changes being inter-modality (77%, intra-modality: 23%).
CONCLUSION: The management is changed in more than one third of patients undergoing SSTR PET/CT even when performed after an (111)In-Octreotide scan. Inter-modality changes were three times more likely than intra-modality changes underlining the clinical impact of SSTR PET/CT.

PMID: 28082438 [PubMed - as supplied by publisher]




Whole body 18F-FDG PET/CT is superior to CT as first line diagnostic imaging in patients referred with serious non-specific symptoms or signs of cancer: a randomized prospective study of 200 patients.
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Whole body 18F-FDG PET/CT is superior to CT as first line diagnostic imaging in patients referred with serious non-specific symptoms or signs of cancer: a randomized prospective study of 200 patients.

J Nucl Med. 2017 Jan 12;:

Authors: Lebech AM, Gaardsting A, Loft A, Graff J, Markova E, Berthelsen AK, Madsen JL, Helms M, Mathiesen LR, David KP, Kronborg G, Kjaer A

Abstract
A fast-track pathway has been established in Denmark to investigate patients with serious non-specific symptoms and signs of cancer (NSSC), which are not eligible to enter an organ-specific cancer program. The prevalence of cancer in this cohort is approximately 20%. The optimal screening strategy in patients with NSSC remains unknown. The aim was to investigate if (18)F-FDG-positron emission tomography/computed tomography (PET/CT) was superior to CT as initial imaging modality in patients with NSSC. In a randomized prospective trial the imaging modalities were compared with regard to diagnostic performance.
METHODS: A total of 200 patients were randomized 1:1 to whole body (18)F-FDG-PET/CT or CT of the thorax and abdomen as imaging modality. A tentative diagnosis was established after first line imaging. The final referral diagnosis was adjudicated by the physician, when sufficient data was available.
RESULTS: A total of 197 patients were available for analysis as 3 patients withdrew consent prior to scan. Thirty-nine (20%) were diagnosed with cancer, 10 (5%) with an infection, 15 (8%) with an autoimmune disease and 76 (39%) with other diseases. In 57 patients (28%) no specific disease was found. Compared to CT scans, (18)F-FDG-PET/CT had a higher specificity (96 vs. 85%; P = 0.028) and a higher accuracy (94 vs. 82%; P = 0.017). However, there were no statistically significant differences in sensitivity (83 vs. 70%) or negative predictive values (96 vs. 92%). No difference in days to final referral diagnosis according to randomization group could be shown (7.2 vs. 7.6 days). However, for the subgroups where the imaging modality showed suspicion of malignancy, there was a significant delay to final diagnosis in the CT group compared to the (18)F-FDG-PET/CT group (11.6 vs. 5.7 days; P = 0.02).
CONCLUSION: We found a higher diagnostic specificity and accuracy of (18)F-FDG-PET/CT compared to CT for detecting cancer in patients with NSSC. (18)F-FDG-PET/CT should therefore be considered as first line imaging in this group of patients.

PMID: 28082437 [PubMed - as supplied by publisher]




Resin versus Glass Microspheres for Yttrium-90 Transarterial Radioembolization: Comparing Survival in Unresectable Hepatocellular Carcinoma using Pretreatment Partition Model Dosimetry.
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Resin versus Glass Microspheres for Yttrium-90 Transarterial Radioembolization: Comparing Survival in Unresectable Hepatocellular Carcinoma using Pretreatment Partition Model Dosimetry.

J Nucl Med. 2017 Jan 12;:

Authors: VAN DER Gucht A, Jreige M, Denys A, Blanc-Durand P, Boubaker A, Pomoni A, Mitsakis P, Silva-Monteiro M, Gnesin S, Nicod-Lalonde M, Duran R, Prior J, Schaefer N

Abstract
The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with Yttrium-90 ((90)Y) transarterial radioembolization (TARE) using pretreatment partition model dosimetry (PMD).
METHODS: We performed a retrospective analysis of prospectively collected data on 77 consecutively treated (mean age 66.4 12.2 y) for uHCC (36 uni-nodular, 5 multi-nodular, 36 diffuse) with (90)Y TARE (41 resin, 36 glass) using pretreatment PMD. Study endpoints were progression-free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier estimates. Several variables including Barcelona Clinic Liver Cancer (BCLC) staging system, tumor size and serum alpha-fetoprotein (AFP) level) were investigated using Cox proportional hazards regression.
RESULTS: Characteristics of two groups were comparable in regard to demographic data, comorbidities, Child-Pugh score, BCLC, serum AFP level and (90)Y global administered activity. Median follow-up time was 7.7 months (range 0.4-50.1). Relapse occurred in 44 patients (57%) at a median of 6 mo (range 0.4-27.9) after (90)Y TARE and 41 patients (53%) died from tumor progression. Comparison between resin and glass microspheres revealed a higher but not statistically significantly PFS and OS rates in (90)Y resin group compared to (90)Y glass group (resin PFS 6.1 mo [95% Confidence interval CI 4.7-7.4] and glass PFS 5 mo [95% CI 0.9-9.2], P = 0.53; resin OS 7.7 mo [95% CI 7.2-8.2] and glass OS 7 mo [95% CI 1.6-12.4], P = 0.77). No significant survival difference between both types of (90)Y microspheres was observed in any subgroups of patients with early/intermediate or advanced BCLC stages. Among the variables investigated Cox analyses showed that only in the glass group, the BCLC staging system and the serum AFP level were associated with PFS (P = 0.04) and OS (P = 0.04). Tumor size was a prognostic factor without significant influence on PFS and OS after (90)Y TARE.
CONCLUSION: Comparison between resin and glass microspheres revealed no significant survival difference in patients treated for uHCC with (90)Y TARE using pretreatment PMD. Further larger prospective studies are warranted to confirm these findings.

PMID: 28082436 [PubMed - as supplied by publisher]




Cumulated activity Comparison of 64Cu-/177Lu-labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model.
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Cumulated activity Comparison of 64Cu-/177Lu-labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model.

J Nucl Med. 2017 Jan 12;:

Authors: Laffon E, Thumerel M, Jougon J, Marthan R

Abstract
OBJECTIVE: This work aimed at estimating kinetic parameters, and hence cumulated activity (AC), of a diagnostic/therapeutic convergence radiopharmaceutical, namely (64)Cu-/(177)Lu-labeled antibody ((64)Cu-/(177)Lu-cetuximab), that acts as anti-epidermal growth factor receptor (EGFR).
METHODS: In mice bearing esophageal squamous cell carcinoma (ESCC) tumor, to estimate uptake (K), release rate constant (kR), and hence cumulated activity, a kinetic model analysis was applied to recently published biodistribution data of immuno-PET imaging with (64)Cu-cetuximab and of micro-SPECT/CT imaging with (177)Lu-cetuximab, including blood and TE-8 tumor.
RESULTS: K, kR and AC were estimated to be: 0.0566/0.0593 g.h-1.g-1, 0.0150/0.0030 h-1 and 2.3 1010/4.1 1012 disintegrations (per gram of TE-8 tumor), with injected activity of 3.70/12.95 MBq for (64)Cu-/(177)Lu-cetuximab, respectively.
CONCLUSION: A model is available for comparing kinetic parameters and cumulated activity of the companion diagnostic/therapeutic (64)Cu-/(177)Lu-cetuximab that may be considered as a step for determining whether one can really use the former to predict dosimetry of the latter.

PMID: 28082435 [PubMed - as supplied by publisher]




89Zr-bevacizumab PET: Potential Early Read Out for Efficacy of Everolimus in Metastatic Renal Cell Carcinoma Patients.
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89Zr-bevacizumab PET: Potential Early Read Out for Efficacy of Everolimus in Metastatic Renal Cell Carcinoma Patients.

J Nucl Med. 2017 Jan 12;:

Authors: van Es SC, Brouwers AH, Mahesh SV, Leliveld-Kors AM, de Jong IJ, Lub-de Hooge MN, de Vries EG, Gietema JA, Oosting SF

Abstract
RATIONALE: Currently, biomarkers that predict efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans in mRCC patients with (89)Zr-bevacizumab, a VEGF-A-binding antibody tracer. Aims were to determine change in tumor tracer uptake after start of everolimus and to explore if (89)Zr-bevacizumab PET can identify patients with early disease progression.
METHODS: (89)Zr-bevacizumab PET was done before and 2 and 6 weeks after start of everolimus 10 mg/day in mRCC patients. Routine CT scans were performed at baseline and every 3 months thereafter. Tumor tracer uptake was quantified using maximum Standardized Uptake Value (SUVmax). Endpoints were change in tumor tracer uptake and treatment response on CT after 3 months.
RESULTS: Thirteen patients participated. Median SUVmax of 94 tumor lesions was 7.3 (range 1.6-59.5). Between patients, median tumor SUVmax varied up to 8-fold. After 2 weeks, median SUVmax was 6.3 (1.7-62.3) corresponding to a mean decrease of 9.1% (P < 0.0001). Three patients discontinued everolimus early. At 6 weeks, a mean decrease in SUVmax of 23.4% compared to baseline was found in 70 evaluable lesions of 10 patients, with a median SUVmax of 5.4 (1.1-49.4, P < 0.0001). All 10 patients who continued treatment had stable disease at 3 months.
CONCLUSION: Everolimus decreases (89)Zr-bevacizumab tumor uptake. Further studies are warranted to evaluate predictive value of (89)Zr-bevacizumab PET for everolimus antitumor efficacy.

PMID: 28082434 [PubMed - as supplied by publisher]




Optimization of labeling PSMAHBED with 68Ga and its quality control systems.
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Optimization of labeling PSMAHBED with 68Ga and its quality control systems.

J Nucl Med. 2017 Jan 12;:

Authors: Eppard E, Homann T, de la Fuente A, Essler M, Roesch F

Abstract
Radiolabeling of the prostate-specific membrane antigen (PSMA) inhibitor, Glu-NH-CO-NH-Lys (Ahx), using the (68)Ga chelator HBED-CC (PSMAHBED) allows imaging of lesions of prostate cancer due to the high expression of PSMA in prostate carcinoma cells as well as bone metastases and lymph nodes related to the disease. The aim of this work was the optimization of the labeling of (68)Ga-PSMAHBED using the efficient cation exchange (CEX) post-processing of (68)Ga as well as the development of a TLC-based quality control system. Labeling was optimized for online ethanol post-processed (68)Ga eluate investigating various parameters, such as buffer molarity (0.1-1 M), temperature (25-90°C), tracer amount (0.11-0.74 nmol) and labeling time. In addition purification of the crude product using a STRATA-X cartridge was tested. For radio-TLC quality control various mobile phases were analyzed using silica gel 60 plates and results were validated using HPLC. The most superior mobile phases were also applied on ITLC-SG-plates. Using optimized conditions labeling yields of > 95% were obtained within 10 min when applying the ethanol-based post-processing using PSMAHBED amounts as low as 0.1 nmol. Higher precursor concentration (0.7 nmol) further increased labeling and quantitative yields to >98% within 5 min. In clinical routine patient batches (> 200 applications) with radiochemical purity > 98 % and specific activities of 326 ± 20 MBq/nmol are obtained reproducibly. Performing TLC quality control on silica gel 60 plates, four mobile phases with suitable separation properties and complementary Rf values were identified. Two systems show equivalent separation on ITLC-SG-plates, with ITLC analysis finished within 5 min in contrast to the TLC system (20 min). Labeling of PSMAHBED was optimized for CEX post-processing methods ensuring almost quantitative labeling and high nuclide purity of final (68)Ga-PSMAHBED, making subsequent purification steps unnecessary. The new radioTLC-method allows quality control in a short time using a fast, reliable, low cost method with little equipment effort. Using this approach, the synthesis is easily adopted by automated synthesis modules such as e.g. the EZAG Modular-Lab eazy.

PMID: 28082433 [PubMed - as supplied by publisher]




Quantification of Lung PET Images: Challenges and Opportunities.
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Quantification of Lung PET Images: Challenges and Opportunities.

J Nucl Med. 2017 Jan 12;:

Authors: Chen DL, Cheriyan J, Chilvers E, Choudoury G, Coello C, Connell M, Fisk M, Groves AM, Gunn RN, Holman BF, Hutton BF, Lee S, MacNee W, Mohan D, Parr D, Subramanian D, Tal-Singer R, Thielemans K, van Beek EJ, Vass L, Wellen JW, Wilkinson I, Wilson FJ

Abstract
Millions of people are affected by respiratory diseases, leading to a significant health burden globally. Due to the current insufficient knowledge of the underlying mechanisms that lead to the development and progression of respiratory diseases, treatment options remain limited. To overcome this limitation and understand the associated molecular changes, non-invasive imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography have been explored for biomarker development, with (18)F-fluorodeoxyglucose ((18)F-FDG) PET imaging being the most studied. The quantification of pulmonary molecular imaging data remains challenging due to variations in tissue, air, blood and water fractions within the lungs. The proportions of these components further differ depending on the lung disease. Therefore, different quantification approaches have been proposed to address these variabilities. However, no standardized approach has been developed to date. This article reviews the data evaluating (18)F-FDG PET quantification approaches in lung diseases, focusing on methods to account for variations in lung components and the interpretation of the derived parameters. The diseases reviewed include acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and interstitial lung disease such as idiopathic pulmonary fibrosis (IPF). Based on review of prior literature, ongoing research and discussions amongst the authors, suggested considerations are presented to assist with the interpretation of the derived parameters from these approaches and the design of future studies.

PMID: 28082432 [PubMed - as supplied by publisher]