PT - JOURNAL ARTICLE AU - Aliaga, Antonio AU - Therriault, Joseph AU - Quispialaya, Kely Monica AU - Aliaga, Arturo AU - Hopewell, Robert AU - Rahmouni, Nesrine AU - Macedo, Arthur C. AU - Kunach, Peter AU - Soucy, Jean-Paul AU - Massarweh, Gassan AU - Diaz, Aida Abreu AU - Pascoal, Tharick A. AU - Rocha, Andreia AU - Guiot, Marie-Christine AU - Machado, Luiza S. AU - De Bastiani, Marco Antônio AU - de Souza, Débora Guerini AU - Souza, Diogo O. AU - Gauthier, Serge AU - Zimmer, Eduardo R. AU - Rosa-Neto, Pedro TI - Comparison Between Brain and Cerebellar Autoradiography Using [<sup>18</sup>F]Flortaucipir, [<sup>18</sup>F]MK6240, and [<sup>18</sup>F]PI2620 in Postmortem Human Brain Tissue AID - 10.2967/jnumed.124.267539 DP - 2025 Jan 01 TA - Journal of Nuclear Medicine PG - 123--129 VI - 66 IP - 1 4099 - http://jnm.snmjournals.org/content/66/1/123.short 4100 - http://jnm.snmjournals.org/content/66/1/123.full SO - J Nucl Med2025 Jan 01; 66 AB - 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.