Comparison Between Brain and Cerebellar Autoradiography Using [¹⁸F]Flortaucipir, [¹⁸F]MK6240, and [¹⁸F]PI2620 in Postmortem Human Brain Tissue

Our objective was to evaluate the in vitro binding properties of [¹⁸F]flortaucipir, 6-(fluoro-¹⁸F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([¹⁸F]MK6240), and 2-(2-([¹⁸F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c']dipyridine ([¹⁸F]PI2620) head-to-head in postmortem human brain tissue. Methods: Autoradiography was used to assess uptake of [¹⁸F]flortaucipir, [¹⁸F]MK6240, and [¹⁸F]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 [¹⁸F]flortaucipir, [¹⁸F]MK6240, and [¹⁸F]PI2620 were calculated from regions of interest manually drawn in the prefrontal, hippocampal, and cerebellar cortices. Results: 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. [¹⁸F]MK6240 and [¹⁸F]PI2620 had higher effect sizes to differentiate control and AD cases than did [¹⁸F]flortaucipir. Bland-Altman analyses revealed strong correlations between [¹⁸F]MK6240, [¹⁸F]PI2620, and [¹⁸F]flortaucipir, with the highest agreement found for [¹⁸F]MK6240 versus [¹⁸F]PI2620. Conclusion: The 3 radioligands showed comparable diagnostic properties to assess tau aggregates in vitro. Binding to AD brain tissues was higher for [¹⁸F]MK6240 and [¹⁸F]PI2620 than for [¹⁸F]flortaucipir. Additionally, [¹⁸F]MK6240 and [¹⁸F]PI2620 had greater selectivity, displaying decreased uptake in control brain tissue compared with [¹⁸F]flortaucipir. These results might provide insights on ongoing initiatives to create a universal scale for tau imaging studies.