A panel of radiochemicals has enabled in-vivo positron emission tomography (PET) of tau pathologies in Alzheimer′s disease (AD), while sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In-vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of ¹⁸F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant PSP tau topologies. Notably, the in-vivo reactivity of ¹⁸F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of autopsied and biopsied brains derived from Pick′s disease, PSP and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of ¹⁸F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on the neuropathological basis.

中文翻译：

---

阿尔茨海默氏病和非阿尔茨海默氏病tauopathies中tau病理的高对比度体内成像

一组放射化学物质已使阿尔茨海默氏病（AD）的tau病变发生了体内正电子发射断层扫描（PET），而对额颞叶变性（FTLD）tau夹杂物的灵敏检测却没有成功。在这里，我们生成了一个成像探针PM-PBB3，用于捕获各种tau沉积物。体外测定证明了该化合物与AD和FTLD中tau病理的反应性。我们还可以将PM-PBB3用于活体鼠tauopathy模型的光学/ PET成像。随后的一项临床PET研究显示，患病患者中¹⁸ F-PM-PBB3的结合增加，反映出皮质占优势的AD和皮质下占优势的PSP tau拓扑结构。值得注意的是，¹⁸的体内反应性F-PM-PBB3与FTLD tau夹杂物得到了接受PET扫描的Pick病，PSP和皮质基底变性患者的尸体解剖和活检大脑的神经病理学检查的大力支持。最后，指示视觉检查¹⁸ F-PM-PBB3-PET图像，以促进基于神经病理学的FTLD多种临床表型的个体化识别。