18F-FDG PET, the early phases and the delivery rate of 18F-AV45 PET as proxies of cerebral blood flow in Alzheimer's disease: Validation against 15O-H2O PET

Introduction: Dual-biomarker positron emission tomography (PET), providing complementary information on cerebral blood flow and amyloid-beta deposition, is of clinical interest for Alzheimer's disease (AD). The purpose of this study was to validate the perfusion components of early-phase F-18-florbetapir (eAV45), the F-18-AV45 delivery rate (R1), and F-18-FDG against O-15-H2O PET and assess how they change with disease severity. Methods: This study included ten controls, 19 amnestic mild cognitive impairment, and 10 AD dementia subjects. Within-subject regional correlations between modalities, between-group regional and voxel-wise analyses of covariance per modality, and receiver operating characteristic analyses for discrimination between groups were performed. Results: FDG standardized uptake value ratio, eAV45 (0-2 min) standardized uptake value ratio, and AV45-R1 were significantly associated with H2O PET (regional Pearson r = 0.54-0.82, 0.70-0.94, and 0.65-0.92, respectively; P < .001). All modalities confirmed reduced cerebral blood flow in the posterior cingulate of patients with amnestic mild cognitive impairment and AD dementia, which was associated with lower cognition (r = 0.36-0.65, P < .025) and could discriminate between patient and control groups (area under the curve > 0.80). However, eAV45 was less sensitive to reflect the disease severity than AV45-R1 or FDG. Discussion: R1 is preferable over eAV45 for accurate representation of brain perfusion in dualbiomarker PET for AD. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.