Willroider Marie, Roeber Sigrun, Horn Anja K E, Arzberger Thomas, Scheifele Maximilian, Respondek Gesine, Sabri Osama, Barthel Henryk, Patt Marianne, Mishchenko Olena, Schildan Andreas, Mueller André, Koglin Norman, Stephens Andrew, Levin Johannes, Höglinger Günter U, Bartenstein Peter, Herms Jochen, Brendel Matthias, Beyer Leonie
Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.
Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany.
Front Neurol. 2021 Jul 2;12:684523. doi: 10.3389/fneur.2021.684523. eCollection 2021.
Autoradiography on brain tissue is used to validate binding targets of newly discovered radiotracers. The purpose of this study was to correlate quantification of autoradiography signal using the novel next-generation tau positron emission tomography (PET) radiotracer [F]PI-2620 with immunohistochemically determined tau-protein load in both formalin-fixed paraffin-embedded (FFPE) and frozen tissue samples of patients with Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP). We applied [F]PI-2620 autoradiography to postmortem cortical brain samples of six patients with AD, five patients with PSP and five healthy controls, respectively. Binding intensity was compared between both tissue types and different disease entities. Autoradiography signal quantification (CWMR = cortex to white matter ratio) was correlated with the immunohistochemically assessed tau load (AT8-staining, %-area) for FFPE and frozen tissue samples in the different disease entities. In AD tissue, relative cortical tracer binding was higher in frozen samples when compared to FFPE samples (CWMR vs. CWMR: 2.5-fold, < 0.001), whereas the opposite was observed in PSP tissue (CWMR vs. CWMR: 0.8-fold, = 0.004). In FFPE samples, [F]PI-2620 autoradiography tracer binding and immunohistochemical tau load correlated significantly for both PSP ( = 0.641, < 0.001) and AD tissue ( = 0.435, = 0.016), indicating a high agreement of relative tracer binding with underlying pathology. In frozen tissue, the correlation between autoradiography and immunohistochemistry was only present in AD ( = 0.417, = 0.014) but not in PSP tissue ( = -0.115, = n.s.). Our head-to-head comparison indicates that FFPE samples show superiority over frozen samples for autoradiography assessment of PSP tau pathology by [F]PI-2620. The [F]PI-2620 autoradiography signal in FFPE samples reflects AT8 positive tau in samples of both PSP and AD patients.
脑组织放射自显影用于验证新发现的放射性示踪剂的结合靶点。本研究的目的是将使用新型下一代tau正电子发射断层扫描（PET）放射性示踪剂[F]PI - 2620的放射自显影信号定量与阿尔茨海默病（AD）和进行性核上性麻痹（PSP）患者的福尔马林固定石蜡包埋（FFPE）和冷冻组织样本中免疫组织化学测定的tau蛋白负荷相关联。我们分别将[F]PI - 2620放射自显影应用于6例AD患者、5例PSP患者和5例健康对照的死后大脑皮质样本。比较了两种组织类型和不同疾病实体之间的结合强度。在不同疾病实体中，对FFPE和冷冻组织样本，放射自显影信号定量（CWMR = 皮质与白质比值）与免疫组织化学评估的tau负荷（AT8染色，面积百分比）相关。在AD组织中，与FFPE样本相比，冷冻样本中的相对皮质示踪剂结合更高（CWMR对CWMR：2.5倍，<0.001），而在PSP组织中观察到相反情况（CWMR对CWMR：0.8倍，=0.004）。在FFPE样本中，[F]PI - 2620放射自显影示踪剂结合与免疫组织化学tau负荷在PSP（=0.641，<0.001）和AD组织（=0.435，=0.016）中均显著相关，表明相对示踪剂结合与潜在病理学高度一致。在冷冻组织中，放射自显影与免疫组织化学之间的相关性仅在AD中存在（=0.417，=0.014），而在PSP组织中不存在（=-0.115，=无显著性差异）。我们的直接比较表明，对于通过[F]PI - 2620对PSP tau病理学进行放射自显影评估，FFPE样本优于冷冻样本。FFPE样本中的[F]PI - 2620放射自显影信号反映了PSP和AD患者样本中AT8阳性tau。
