Cross-Sectional and Longitudinal Comparison of Tau Imaging with 18F-MK6240 and 18F-Flortaucipir in Populations Matched for Age, MMSE and Brain Beta-Amyloid Burden

ObjectivesLongitudinal tau quantification may provide a useful marker of drug efficacy in clinical trials. Different tau PET tracers may have different sensitivity to longitudinal changes, but without a head-to-head dataset or a carefully designed case-matching procedure, comparing results in different cohorts can be biased. In this study, we compared the tau PET tracers, F-18-MK6240 and F-18-flortaucipir (FTP), both cross-sectionally and longitudinally by case-matching subjects in the AIBL and ADNI longitudinal cohort studies.MethodsA subset of 113 participants from AIBL and 113 from ADNI imaged using F-18-MK6240 and F-18-FTP respectively, with baseline and follow-up, were matched based on baseline clinical diagnosis, MMSE, age and amyloid (A beta) PET centiloid value. Subjects were grouped as 64 A beta- cognitively unimpaired (CU), 22 A beta+ CU, 14 A beta+ mild cognitive impairment (MCI) and 13 A beta+ Alzheimer's disease (AD). Tracer retention was measured in the mesial, temporoparietal, rest of the cortex, and a meta-temporal region composed of entorhinal, inferior/ middle temporal, fusiform, parahippocampus and amygdala. T-tests were employed to assess group separation at baseline using SUVR Z-scores and longitudinally using SUVR%/Yr.ResultsBoth tracers detected statistically significant differences at baseline in most regions between all clinical groups. Only F-18-MK6240 showed statistically significant higher rate of SUVR increase in A beta+ CU compared to A beta- CU in the mesial, meta-temporal and temporoparietal regions.Conclusion(18)F-MK6240 appears to be a more sensitive tracer for change in tau level at the preclinical stage of AD.