Comparison Between Brain and Cerebellar Autoradiography Using [F]Flortaucipir, [F]MK6240, and [F]PI2620 in Postmortem Human Brain Tissue.

Our objective was to evaluate the in vitro binding properties of [F]flortaucipir, 6-(fluoro-F)-3-(1-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([F]MK6240), and 2-(2-([F]fluoro)pyridin-4-yl)-9-pyrrolo[2,3-b:4,5c']dipyridine ([F]PI2620) head-to-head in postmortem human brain tissue. Autoradiography was used to assess uptake of [F]flortaucipir, [F]MK6240, and [F]PI2620 in control and Alzheimer disease (AD) autopsy-confirmed brain tissues. The study focused on the analysis of the prefrontal cortex, hippocampus, and cerebellum sections in 12 controls and 12 AD cases, as well as whole-brain hemisphere in 1 control and 1 AD sample, for each radiotracer. The binding values of [F]flortaucipir, [F]MK6240, and [F]PI2620 were calculated from regions of interest manually drawn in the prefrontal, hippocampal, and cerebellar cortices. For all 3 radioligands investigated, we observed significant tracer binding differences between control and AD tissues in the whole-brain hemisphere, prefrontal cortex, and hippocampus but not in the cerebellar cortex. [F]MK6240 and [F]PI2620 had higher effect sizes to differentiate control and AD cases than did [F]flortaucipir. Bland-Altman analyses revealed strong correlations between [F]MK6240, [F]PI2620, and [F]flortaucipir, with the highest agreement found for [F]MK6240 versus [F]PI2620. The 3 radioligands showed comparable diagnostic properties to assess tau aggregates in vitro. Binding to AD brain tissues was higher for [F]MK6240 and [F]PI2620 than for [F]flortaucipir. Additionally, [F]MK6240 and [F]PI2620 had greater selectivity, displaying decreased uptake in control brain tissue compared with [F]flortaucipir. These results might provide insights on ongoing initiatives to create a universal scale for tau imaging studies.