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.

我们的目的是评估 [¹⁸F]flortaucipir、6-（氟-¹⁸F）-3-（1H-吡咯并[2,3-c]吡咯烷-1-基）异喹啉-5-胺 （^[18F]MK6240） 和 2-（2-（[¹⁸F]氟）吡啶-4-基）-9H-吡咯并[2,3-b：4,5c′]二吡啶 （[¹⁸F]PI2620） 在死后人脑组织中头对头的结合特性。方法：放射自显影用于评估对照和阿尔茨海默病 （AD） 尸检证实的脑组织中 [¹⁸F] flortaucipir 、 [¹⁸F] MK6240 和 [¹⁸F] PI2620 的摄取。该研究的重点是分析每种放射性示踪剂的 12 例对照和 12 例 AD 病例的前额叶皮层、海马体和小脑切片，以及 1 例对照和 1 例 AD 样本的全脑半球。[¹⁸F]flortaucipir、[¹⁸F]MK6240 和 [¹⁸F]PI2620 的结合值是根据前额叶、海马和小脑皮层中手动绘制的感兴趣区域计算的。结果：对于研究的所有 3 个放射配体，我们在全脑半球、前额叶皮层和海马体中观察到对照组织和 AD 组织之间存在显着的示踪剂结合差异，但在小脑皮层中没有。[¹⁸个地址]MK6240 和 [¹⁸F]PI2620 在区分对照和 AD 病例方面比 [¹⁸F] flortaucipir 具有更高的效应量。Bland-Altman 分析显示 [¹⁸F]MK6240、[¹⁸F]PI2620 和 [¹⁸F]flortaucipir 之间具有很强的相关性，其中 [¹⁸F]MK6240 与 [¹⁸F]PI2620 的一致性最高。结论：3 种放射性配体在体外评估 tau 聚集体方面显示出相似的诊断特性。 [¹⁸F]MK6240 和 [¹⁸F]PI2620 与 AD 脑组织的结合高于 [¹⁸F]flortaucipir。此外，[¹⁸F]MK6240 和 [¹⁸F]PI2620 具有更高的选择性，与 [¹⁸F] flortaucipir 相比，在对照脑组织中的摄取降低。这些结果可能为正在进行的为 tau 成像研究创建通用量表的计划提供见解。