For amyloid positron emission tomography tracers, the simplified reference tissue model derived ratio of influx rate in target relative to reference region (R1) has been shown to serve as a marker of brain perfusion, and, due to the strong coupling between perfusion and metabolism, as a proxy for glucose metabolism. In the present study, 11 prodromal Alzheimer's disease and nine Alzheimer's disease dementia patients underwent [18F]THK5317, carbon-11 Pittsburgh Compound-B ([11C]PIB), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography to assess the possible use of early-phase [18F]THK5317 and R1 as proxies for brain perfusion, and thus, for glucose metabolism. Discriminative performance (prodromal vs Alzheimer's disease dementia) of [18F]THK5317 (early-phase SUVr and R1) was compared with that of [11C]PIB (early-phase SUVr and R1) and [18F]FDG. Strong positive correlations were found between [18F]THK5317 (early-phase, R1) and [18F]FDG, particularly in frontal and temporoparietal regions. Differences in correlations between early-phase and R1 ([18F]THK5317 and [11C]PIB) and [18F]FDG, were not statistically significant, nor were differences in area under the curve values in the discriminative analysis. Our findings suggest that early-phase [18F]THK5317 and R1 provide information on brain perfusion, closely related to glucose metabolism. As such, a single positron emission tomography study with [18F]THK5317 may provide information about both tau pathology and brain perfusion in Alzheimer's disease, with potential clinical applications.
Keywords: 2-deoxy-2-[18F]fluoro-D-glucose; Alzheimer’s disease; early-phase [18F]THK5317 positron emission tomography; early-phase carbon-11 Pittsburgh Compound-B; simplified reference tissue model R1.