Longitudinal tau PET using 18 F-flortaucipir: the Effect of relative Cerebral Blood Flow on (semi)quantitative parameters.

Semi-quantitative positron emission tomography (PET) measures (standardized uptake value ratio (SUVr)) have several advantages over quantitative measures, such as practical applicability and relative computational simplicity. However, semi-quantitative measures may potentially be affected by changes in blood flow, whereas quantitative measures such as binding potential (BPND) are not. For [ 18 F]flortaucipir PET the sensitivity of SUVr for changes in blood flow has not been investigated yet. This is important, because [ 18 F]flortaucipir PET is an important outcome measure in clinical trials for Alzheimer's disease. Therefore we compared semi-quantitative (SUVr) and quantitative (R1, BPND) parameters of longitudinal [ 18 F]flortaucipir PET scans, and assessed their vulnerability to changes in blood flow. Subjects with subjective cognitive decline (SCD; n = 38) and Alzheimer's disease (AD) patients ( n = 24) underwent baseline (BL) and 2-year follow-up (FU) dynamic [ 18 F]flortaucipir PET scans. BPND and R1 were estimated using receptor parametric mapping (RPM) and SUVr(80-100min) was calculated. For each region-of-interest ((trans)entorhinal, limbic and neocortical) and parameter, %change was calculated. Regional SUVrs were compared to corresponding DVR (= BPND+1) using paired T-tests. Additionally, simulations were performed to model effects of (large(r)) flow changes on BPND and SUVr in different binding categories. Thereafter, %bias for SUVr with respect to underlying binding and flow were evaluated. Results in SCD and AD showed only minor differences between SUVr and BPND %change. R1 changes were small (+0.7% in SCD and -1.6% in AD). Simulations illustrated a variable %bias for SUVr depending on the underlying binding condition. Concluding, in line with established practices, SUVr provided an accurate estimate of specific binding for [ 18 F]flortaucipir over a two-year follow-up during which changes in flow were small, also in AD patients. Notwithstanding, simulations showed that large(r) flow changes may potentially affect [ 18 F]flortaucipir SUVr. Given that it is currently unknown to what order of magnitude pharmacotherapeutic interventions may induce changes in cerebral blood flow, caution may be warranted in situations where changes in flow are large(r) and DVR/BPND may be preferred in such conditions to ensure representative quantification of [ 18 F]flortaucipir PET images.