Description: Training for accurate image interpretation is essential for the clinical use of β-amyloid PET imaging, but the role of interpreter training and the accuracy of the algorithm for routine visual assessment of florbetaben PET scans are unclear. The aim of this study was to test the robustness of the visual assessment method for florbetaben scans, comparing efficacy readouts across different interpreters and training methods and against a histopathology standard of truth (SoT). Methods: Analysis was based on data from an international open-label, nonrandomized, multicenter phase-3 study in patients with or without dementia ( ClinicalTrials.gov : NCT01020838). Florbetaben scans were assessed visually and quantitatively, and results were compared with amyloid plaque scores. For visual assessment, either in-person training ( n = 3 expert interpreters) or an electronic training method ( n = 5 naïve interpreters) was used. Brain samples from participants who died during the study were used to determine the histopathologic SoT using Bielschowsky silver staining (BSS) and immunohistochemistry for β-amyloid plaques. Results: Data were available from 82 patients who died and underwent postmortem histopathology. When visual assessment results were compared with BSS + immunohistochemistry as SoT, median sensitivity was 98.2% for the in-person–trained interpreters and 96.4% for the e-trained interpreters, and median specificity was 92.3% and 88.5%, respectively. Median accuracy was 95.1% and 91.5%, respectively. On the basis of BSS only as the SoT, median sensitivity was 98.1% and 96.2%, respectively; median specificity was 80.0% and 76.7%, respectively; and median accuracy was 91.5% and 86.6%, respectively. Interinterpreter agreement (Fleiss ) was excellent (0.89) for in-person–trained interpreters and very good (0.71) for e-trained interpreters. Median intrainterpreter agreement was 0.9 for both in-person–trained and e-trained interpreters. Visual and quantitative assessments were concordant in 88.9% of scans for in-person–trained interpreters and in 87.7% of scans for e-trained interpreters. Conclusion: Visual assessment of florbetaben images was robust in challenging scans from elderly end-of-life individuals. Sensitivity, specificity, and interinterpreter agreement were high, independent of expertise and training method. Visual assessment was accurate and reliable for detection of plaques using BSS and immunohistochemistry and well correlated with quantitative assessments.

Description: Thromboembolic diseases such as myocardial infarction, stroke, transient ischemic attacks, and pulmonary embolism are major causes of morbidity and mortality worldwide. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the key receptor involved in platelet aggregation and is a validated target for therapeutic approaches and diagnostic imaging. The aim of this study was to develop and characterize a specific small-molecule tracer for PET imaging that binds with high affinity to GPIIb/IIIa receptors and has suitable pharmacokinetic properties to overcome limitations of previous approaches. Methods: Binding of 18 F-GP1 to GPIIb/IIIa receptors was investigated in competition binding assays and autoradiography using a fresh cardiac thrombus from an explanted human heart. The clot-to-blood ratio for 18 F-GP1 was investigated by an in vitro blood flow model. Biodistribution and thrombus detection was investigated in cynomolgus monkeys after insertion of a roughened catheter into either the vena cava or the aorta. Results: 18 F-GP1 is an 18 F-labeled small molecule for PET imaging of thrombi. The half maximal inhibitory concentration of 18 F-GP1 to GPIIb/IIIa was 20 nM. 18 F-GP1 bound to thrombi with a mean clot-to-blood ratio of 95. Binding was specific and can be displaced by excess nonradioactive derivative. Binding was not affected by anticoagulants such as aspirin or heparin. 18 F-GP1 showed rapid blood clearance and a low background after intravenous injection in cynomolgus monkeys. Small arterial, venous thrombi, thrombotic depositions on damaged endothelial surface, and small cerebral emboli were detected in vivo by PET imaging. Conclusions: 18 F-GP1 binds specifically with high affinity to the GPIIb/IIIa receptor involved in platelet aggregation. Because of its favorable preclinical characteristics, 18 F-GP1 is currently being investigated in a human clinical study.

Description: (4 S )-4-(3- 18 F-fluoropropyl)- l -glutamate ( 18 F-FSPG, or BAY 94-9392) is a new tracer to assess system x C transporter activity with PET. The aim of this study was to explore the tumor detection rate of 18 F-FSPG, compared with that of 18 F-FDG, in patients with hepatocellular carcinoma (HCC). Methods: Preclinically, in vivo HCC models of orthotopically implanted Huh7 and MH3924a cancer cells were studied with 18 F-FSPG in Naval Medical Research Institute nude mice ( n = 3) and August-Copenhagen Irish rats ( n = 4), respectively. Clinically, 5 patients with HCC who had hyper- or isometabolic lesions on 18 F-FDG PET were enrolled for evaluation of the tracer. Dynamic whole-body PET images with 18 F-FSPG were acquired for up to 120 min after injection of approximately 300 MBq of 18 F-FSPG. Immunohistochemical expression levels of the xCT subunit of the system x C and CD44 of HCC were studied in 4 patients with HCC. Results: Strong tumor uptake and low background from nontarget tissue allowed excellent tumor visualization in animal models with orthotopically implanted liver tumors. 18 F-FSPG PET procedures were well tolerated in all patients. 18 F-FSPG PET and 18 F-FDG detected lesions in 5 of 5 and 3 of 5 patients, respectively. The maximal standardized uptake values (SUV) were comparable ( 18 F-FSPG, 4.7 ± 3.2; 18 F-FDG, 6.1 ± 2.9). The ratios of maximal SUV of the tumor to mean SUV of normal liver were also comparable ( 18 F-FSPG, 3.6 ± 2.2; 18 F-FDG, 2.7 ± 1.3), but the mean SUV of normal liver of 18 F-FSPG was significantly lower than that of 18 F-FDG ( P 〈 0.05). Two patients with HCC who showed both xCT and CD44 expression had moderate or intense accumulation of 18 F-FSPG, but the remaining 2 patients with negative CD44 expression showed mild uptake. Conclusion: 18 F-FSPG was successfully translated from preclinical evaluation into patients with HCC. 18 F-FSPG may be a promising tumor PET agent with a high cancer detection rate in patients with HCC.