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: 18 F-labeled N , N -diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide (DPA-714) is a radioligand for the 18-kDa translocator protein. The purpose of the present study was to identify the best method for generating quantitative parametric images of 18 F-DPA-714 binding. Methods: Ninety-minute dynamic 18 F-DPA-714 PET scans with full arterial sampling from 6 healthy subjects and 9 Alzheimer disease (AD) patients were used. Plasma-input–based Logan graphical analysis and spectral analysis were used to generate parametric volume of distribution (V T ) images. Five versions of Ichise, reference Logan, and 2 basis function implementations (receptor parametric mapping and simplified reference tissue model 2 [SRTM2]) of SRTM, all using gray matter cerebellum as the reference region, were applied to generate nondisplaceable binding potential (BP ND ) images. Results: Plasma-input Logan analysis ( r 2 = 0.99; slope, 0.88) and spectral analysis ( r 2 = 0.99, slope, 0.93) generated estimates of V T that correlated well with values obtained using nonlinear regression. BP ND values generated using SRTM2 ( r 2 = 0.83; slope, 0.95) and reference Logan analysis ( r 2 = 0.88; slope, 1.01) correlated well with nonlinear regression–based estimates. Conclusion: Both Logan analysis and spectral analysis can be used to obtain quantitatively accurate V T images of 18 F-DPA-714. In addition, SRTM2 and reference Logan analysis can provide accurate BP ND images. These parametric images could be used for voxel-based comparisons.

Description: SUV ratios (SUVRs) are used for relative quantification of 18 F-florbetaben scans. The cerebellar cortex can be used as a reference region for quantification. However, cerebellar amyloid-β (Aβ) plaques may be present in Alzheimer disease (AD). The aim of this study was to assess the influence of Aβ pathology, including neuritic plaques, diffuse plaques, and vascular deposits, in 18 F-florbetaben SUVR when cerebellum is used as the reference. Methods: Using immunohistochemistry to demonstrate Aβ plaques and vascular deposits, and using the Bielschowsky method to demonstrate neuritic plaques, we performed a neuropathologic assessment of the frontal, occipital, anterior cingulate, and posterior cingulate cerebral cortices and the cerebellar cortex of 87 end-of-life patients (64 with AD, 14 with other types of dementia, and 9 nondemented aged volunteers; mean age ± SD, 80.4 ± 10.2 y) who had undergone 18 F-florbetaben PET before death. The lesions were rated as absent (none or sparse) or present (moderate or frequent). Mean cortical SUVRs were compared among cases with different cerebellar Aβ loads. Results: None of the 83 evaluable cerebellar samples showed frequent diffuse Aβ or neuritic plaques; 8 samples showed frequent vascular Aβ deposits. Diffuse Aβ plaques were rated as absent in 78 samples (94%) and present in 5 samples (6%). Vascular Aβ was rated as absent in 62 samples (74.7%) and present in 21 samples (25.3%). No significant differences in cerebellar SUVs were found among cases with different amounts or types of Aβ deposits in the cerebral cortex. Both diffuse and neuritic plaques were found in the cerebral cortex of 26–44 cases. No significant SUVR differences were found between these brains with different cerebellar Aβ loads. Conclusion: The effect of cerebellar plaques on cortical 18 F-florbetaben SUVRs appears to be negligible even in advanced stages of AD with a higher cerebellar Aβ load.

Description: 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) is a radiopharmaceutical depicting tumor cell proliferation with PET. In malignancies of the lung, breast, head and neck, digestive tract, brain, and other organs, quantitative assessment of 18 F-FLT targeting has been shown to correlate with the proliferation marker Ki-67 and with clinical outcome measures such as time to progression and overall survival (OS). The aim of this study was to assess various PET segmentation methods to estimate the proliferative volume (PV) and their prognostic value for OS in patients with suspected high-grade glioma. Methods: Twenty-six consecutive patients underwent preoperative 18 F-FLT PET/CT and T1-weighted MRI of the brain after contrast application. The maximum standardized uptake value (SUV max ) of all tumors was calculated, and 3 different segmentation methods for estimating the PV were used: the 50% isocontour of the SUV max signal for the PV 50% , the signal-to-background ratio (SBR) for an adaptive threshold delineation (PV SBR ) method, and the iterative background-subtracted relative threshold level (RTL) method to estimate the PV RTL . The prognostic value of the SUV max and the different PVs for OS were assessed. Results: Twenty-two patients had glioblastoma multiforme, 2 had anaplastic oligodendroglioma, 1 had anaplastic ependymoma, and 1 had anaplastic astrocytoma. The median OS was 397 d (95% confidence interval, 204–577); 19 patients died during the follow-up period. The PV SBR showed a significantly ( P = 0.002) better association with OS than did SUV max , PV RTL , and PV 50% . Receiver-operating-characteristic analysis resulted in a threshold volume for the PV SBR of 11.4 cm 3 , with a sensitivity and specificity of 70% and 83%, respectively, for the prediction of OS. Kaplan–Meier analyses showed a significant discrimination between short and long OS ( P = 0.024, log rank) for this threshold. Conclusion: The PV as determined by 18 F-FLT PET is associated with OS in high-grade malignant gliomas. The SBR method yielded the best results to predict short and long OS.