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  • 1
    Publication Date: 2018-12-04
    Description: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)–targeted PET imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18 F-DCFPyL (2-(3-{1-carboxy-5-[(6- 18 F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET examinations in a prospective setting mimicking the typical clinical workflow at a prostate cancer referral center. Methods: Four readers (2 experienced readers (ERs, 〉3 y of PSMA-targeted PET interpretation experience) and 2 inexperienced readers (IRs, 〈1 y of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18 F-DCFPyL PET/CT studies independently. Per scan, a maximum of 5 target lesions was selected by the observers, and a PSMA-RADS score for every target lesion was recorded. No specific preexisting conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated, and interobserver agreement rates on a target lesion–based, on an organ-based, and on an overall PSMA-RADS score–based level were computed. Results: The number of target lesions identified by each observer was as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least 2 individual observers (all 4 readers selected the same target lesion in 58 of 125 [46.4%] instances, 3 readers in 40 of 125 [32%], and 2 observers in 27 of 125 [21.6%]). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient [ICC] for 4, 3, and 2 identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC, 0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC, 0.84), with a significant difference for ER (ICC, 0.97) vs. IR (ICC, 0.74) ( P = 0.005). Conclusion: PSMA-RADS demonstrated a high concordance rate in this study, even among readers with different levels of experience. This finding suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 2
    Publication Date: 2018-09-05
    Description: Altered myocardial perfusion is a common finding in chronic Chagas cardiomyopathy (CCC), but its underlying histologic changes have not been elucidated. We investigated the occurrence of myocardial perfusion defects (MPDs) and the correlated regional changes to histology in an experimental model of CCC in hamsters. Methods: Female Syrian hamsters ( n = 34) were infected with 3.5 x 10 4 to 10 5 trypomastigote forms of Trypanosoma cruzi, Y strain, and 6–10 mo afterward underwent in vivo imaging including resting 99m Tc-sestamibi SPECT, segmental and global left ventricular function assessment using 2-dimensional echocardiography, and 18 F-FDG PET for evaluation of myocardial viability. Histologic analysis included quantification of fibrosis, inflammatory infiltration, and the diameter and density of myocardial microcirculation. Results: MPDs were present in 17 (50%) of the infected animals. Histologic analysis revealed no transmural scar in segments with an MPD, and normal or mildly reduced 18 F-FDG uptake, indicating viable myocardium. Infected animals with an MPD, in comparison to infected animals without an MPD and control animals, showed a lower left ventricular ejection fraction ( P = 0.012), a higher wall motion score index ( P = 0.004), and a higher extent of inflammatory infiltration ( P = 0.018) but a similar extent of fibrosis ( P = 0.15) and similar microvascular diameter and density ( P 〉 0.05). Segments with an MPD ( n = 65), as compared with normally perfused regions in the same animal ( n = 156), showed a higher wall motion score index ( P = 0.005) but a similar extent of inflammatory infiltration, a similar extent of fibrosis, and a similar microvascular diameter and density. Conclusion: Resting MPDs are frequent in experimental CCC and are associated with myocardial inflammation but do not designate scar tissue, corresponding to regions with metabolically viable myocardium.
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    Topics: Medicine
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  • 3
    Publication Date: 2018-05-02
    Description: 18 F- or 131 I-labeled (4-fluoro-3-iodobenzyl)guanidine (FIBG) has been a promising yet unattainable derivative of radioiodine-labeled meta-iodobenzylguanidine (MIBG), because of the complex radiofluorination method. In this study, we proposed a 2-step radiosynthetic method to obtain 18 F-FIBG and evaluated the diagnostic and therapeutic potential of 18 F-FIBG and 131 I-FIBG in a pheochromocytoma model (PC-12). Methods: 18 F-FIBG was prepared from a (mesityl)(aryl)iodonium salt precursor in the presence of a copper catalyst. Biodistribution studies, PET imaging, and a therapeutic study were performed on the PC-12 xenograft mice with either 18 F- or 131 I-FIBG. The association between the therapeutic effect and the tumor uptake of pretherapy 18 F-FIBG PET was also evaluated. Results: The copper-mediated radiofluorination method readily yielded 18 F-FIBG, as well as its regioisomer, 18 F-IFBG. The isolated 18 F-FIBG showed a higher accumulation in the PC-12 xenograft tumor than in any other tissue. The high tumor uptake of 18 F-FIBG allowed clear tumor visualization in the PET images as early as 1 h after injection, with an excellent tumor-to-background ratio. A biodistribution study with 131 I-FIBG revealed its higher and prolonged retention in the tumor in comparison with 125 I-MIBG. As a result, a therapeutic dose of 131 I-FIBG delayed tumor growth significantly more than did 131 I-MIBG. The tumor uptake of 18 F-FIBG was proportional to the therapeutic effect of 131 I-FIBG. Conclusion: These results suggest the potential usefulness of FIBG as a diagnostic and therapeutic agent for the management of norepinephrine transporter (NET)–expressing tumors.
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    Topics: Medicine
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  • 4
    Publication Date: 2018-07-03
    Description: Reliable standards and criteria for somatostatin receptor (SSTR) PET are still lacking. We herein propose a structured reporting system on a 5-point scale for SSTR PET imaging, titled SSTR-RADS version 1.0, which might serve as a standardized assessment for both diagnosis and treatment planning in neuroendocrine tumors. SSTR-RADS could guide the imaging specialist in interpreting SSTR PET scans, facilitate communication with the referring clinician so that appropriate workup for equivocal findings is pursued, and serve as a reliable tool for patient selection for planned peptide receptor radionuclide therapy.
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    Topics: Medicine
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  • 5
    Publication Date: 2018-07-03
    Description: 123 I-metaiodobenzylguanidine ( 123 I-MIBG) has independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not affect its quantitative information. We evaluated whether the 4 classes of antidepressants currently most prescribed as first-line treatment for major depressive disorder (MDD) have the potential to alter 123 I-MIBG imaging results. Methods: The inhibition effect of desipramine, escitalopram, venlafaxine, and bupropion on 131 I-MIBG uptake was assessed by in vitro uptake assays using human neuroblastoma SK-N-SH cells. The half-maximal inhibitory concentration of tracer uptake was determined from dose–response curves. To evaluate the effect of intravenous pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5 or 15 mg/kg) on 123 I-MIBG cardiac uptake, in vivo planar 123 I-MIBG scanning of healthy New Zealand White rabbits was performed. Results: The half-maximal inhibitory concentrations of desipramine, escitalopram, venlafaxine, and bupropion on 131 I-MIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (as derived by previous clinical trials), the inhibition rates of 131 I-MIBG uptake were 90.6% for desipramine, 25.5% for venlafaxine, 11.7% for bupropion, and 0.72% for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in vivo rabbit model: with a dosage considerably higher than used in clinical practice, the noninhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine markedly reduced cardiac 123 I-MIBG uptake. Conclusion: In the present in vitro binding assay and in vivo rabbit study, the selective serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac 123 I-MIBG uptake within therapeutic dose ranges, whereas other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac 123 I-MIBG imaging, in particular, if the patient’s neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine-interfering antidepressant.
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  • 6
    Publication Date: 2018-06-02
    Description: Fibrillary tau aggregates in Alzheimer disease and allied neurodegenerative disorders have been visualized in vivo by PET, whereas mechanistic links between PET-detectable tau deposits and neurotoxicity remain elusive. Here, we took advantage of transgenic mouse models of tauopathies to evaluate associations between PET and postmortem measures of tau probe binding and their relation to neuronal loss. Methods: PET with a tau probe, 11 C-PBB3 (2-((1E,3E)-4-(6-( 11 C-methylamino)pyridine-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol), and volumetric MRI were performed for transgenic rTg4510 mice and nontransgenic mice. Binding of 11 C-PBB3 and its blockade by another tau binding compound, AV-1451 (-(6-fluoropyridine-3-yl)-5H-pyrido[4,3-b]indole), in homogenized brains of tauopathy patients and rTg4510 and PS19 mice were quantified, and 11 C-PBB3–positive and phosphorylated tau lesions in sectioned brains of these mice were assessed. Results: In vivo 11 C-PBB3 binding to the rTg4510 neocortex/hippocampus was increased relative to controls and correlated with local atrophy. In vitro 11 C-PBB3 binding in the neocortex/hippocampus also correlated well with in vivo radioligand binding and regional atrophy in the same individual rTg4510 mice. By contrast, in vitro 11 C-PBB3 binding was elevated in the brain stem but not hippocampus of PS19 mice, despite a pronounced loss of neurons in the hippocampus rather than brain stem. Finally, 11 C-PBB3 and AV-1451 showed similar binding properties between mouse models and tauopathy patients. Conclusion: The present findings support the distinct utilities of 11 C-PBB3 PET and MRI in rTg4510 and PS19 mice for quantitatively pursuing mechanisms connecting PET-detectable and PET-undetectable tau aggregations to neuronal death, which recapitulate 2 different modes of tau-provoked neurotoxicity.
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  • 7
    Publication Date: 2018-05-02
    Description: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKIs). We aimed to assess the role of metabolic imaging using 18 F-FDG PET/CT shortly before and 3 mo after initiation of TKI treatment. Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline 18 F-FDG PET/CT before and 3 mo after TKI treatment initiation. During follow-up, CT scans were obtained every 3 mo and analyzed according to RECIST. The predictive value for estimating progression-free survival (PFS) and overall survival (OS) was examined by investigating the 18 F-FDG SUV mean/max of the metabolically most active lesion, as well as by analyzing clinical parameters (tumor marker doubling times [calcitonin, carcinoembryonic antigen], prior therapies, rearranged-during-transfection mutational status, and disease type). Results: Within a median follow-up of 5.2 y, 9 patients experienced disease progression after a median interval of 2.1 y, whereas the remainder had ongoing disease control (5 with a partial response and 4 with stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5 y after TKI initiation. A pretherapeutic SUV mean of more than 4.0 predicted a significantly shorter PFS (1.9 y vs. 5.2 y, P = 0.04). Furthermore, sustained high 18 F-FDG uptake at 3 mo with a SUV mean of more than 2.8 tended to portend an unfavorable prognosis, with a PFS of 1.9 y (vs. 3.5 y, P = 0.3). Prolonged carcinoembryonic antigen doubling times were significantly correlated with longer PFS ( r = 0.7) and OS ( r = 0.76, P 〈 0.01). None of the other clinical parameters had prognostic significance. Conclusion: Pretherapeutic 18 F-FDG PET/CT provides prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. A low tumor metabolism with an SUV mean of less than 4.0 before treatment predicts a longer PFS.
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  • 8
    Publication Date: 2018-05-02
    Description: Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P 〈 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.
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    Topics: Medicine
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