Imaging tau pathology in Parkinsonisms.
Imaging tau pathology in Parkinsonisms.
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DOI：
10.1038/s41531-017-0023-3
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Strafella AP
中科院分区：
文献类型：
--
作者：
Coakeley S;Strafella AP
正电子发射断层扫描放射性示踪剂在体内靶向病理tau的最新进展导致了大量的人体试验。虽然研究主要集中在最常见的肌萎缩侧索硬化症--阿尔茨海默病上，但也有必要对帕金森氏症的肌萎缩侧索硬化症进行检测，例如进行性核上性瘫痪、皮质基底膜变性、与17号染色体相关的额颞痴呆和帕金森症。不同疾病的tau聚集体的异构体和构象不同，因此，一个放射性示踪剂可能不适合所有的tauopy病。在这篇综述中，我们评估了目前治疗帕金森病的tau放射性示踪剂的临床前和临床报道。这些示踪剂包括[18F]FDDNP、[11C]PBB3、[18F]THK-5317、[18F]THK-5351和[18F]AV-1451([18F]T807)。人们担心与[18F]FDDNP和[11C]PBB3的靶外结合可能会增加信噪比，从而降低这些放射性示踪剂的疗效。[18F]THK-5317、[18F]THK-5351和[18F]AV-1451已经在进行性核上性麻痹患者中进行了检测，而[18F]THK-5317和[18F]AV-1451也已经在皮质基底膜变性患者中进行了检测。[18F][18F]THK-5317和[18F]THK-5351已证明结合在已知患有病理性tau的大脑区域；然而，由于样本量较小，在得出它们在帕金森病tau病中的适用性之前，应重复这些研究。[18F]在进行性核上性瘫痪患者中，AV-1451的结果喜忧参半，尸检分析显示，与非阿尔茨海默病患者脑片的结合很少，甚至没有。
The recent development of positron emission tomography radiotracers targeting pathological tau in vivo has led to numerous human trials. While investigations have primarily focused on the most common tauopathy, Alzheimer’s disease, it is imperative that testing also be performed in parkinsonian tauopathies, such as progressive supranuclear palsy, corticobasal degeneration, and frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregates differ in isoforms and conformations across disorders, and as a result one radiotracer may not be appropriate for all tauopathies. In this review, we evaluate the preclinical and clinical reports of current tau radiotracers in parkinsonian disorders. These radiotracers include [18F]FDDNP, [11C]PBB3, [18F]THK-5317, [18F]THK-5351, and [18F]AV-1451 ([18F]T807). There are concerns of off-target binding with [18F]FDDNP and [11C]PBB3, which may increase the signal to noise ratio and thereby decrease the efficacy of these radiotracers. Testing in [18F]THK-5317, [18F]THK-5351, and [18F]AV-1451 has been performed in progressive supranuclear palsy, while [18F]THK-5317 and [18F]AV-1451 have also been tested in corticobasal degeneration patients. [18F]THK-5317 and [18F]THK-5351 have demonstrated binding in brain regions known to be afflicted with pathological tau; however, due to small sample sizes these studies should be replicated before concluding their appropriateness in parkinsonian tauopathies. [18F]AV-1451 has demonstrated mixed results in progressive supranuclear palsy patients and post-mortem analysis shows minimal to no binding to non-Alzheimer’s disease tauopathies brain slices.