Mena Anastassia M, Strafella Antonio P
Brain Health Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada.
Institute of Medical Science, University of Toronto, Ontario, Canada.
Clin Park Relat Disord. 2022 Jul 16;7:100155. doi: 10.1016/j.prdoa.2022.100155. eCollection 2022.
Atypical parkinsonisms (APs) are a group of diseases linked to tau pathology. These include progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). In the initial stages, these APs may have similar clinical manifestations to Parkinson's disease (PD) and other parkinsonisms: bradykinesia, postural instability, tremor, and cognitive decline. Because of this, one major hurdle is the accurate early diagnosis of APs. Recent advances in positron emission tomography (PET) radiotracer development have allowed for targeting pathological tau in Alzheimer's disease (AD). Currently, work is still in progress for identifying a first-in-class radiotracer for imaging tau in APs. In this review, we evaluate the literature on in vitro and in vivo testing of current tau PET radiotracers in APs. The tau PET tracers assessed include both first-generation tracers ([18F]AV-1451, [18F]FDDNP, [18F]THK derivatives, and [11C]PBB3) and second-generation tracers ([18F]PM-PBB3, [18F]PI-2620, [18F]RO-948, [18F]JNJ-067, [18F]MK-6240, and [18F]CBD-2115). Concerns regarding off-target binding to cerebral white matter and the basal ganglia are still prominent with first-generation tracers, but this seems to have been mediated in a handful of second-generation tracers, including [18F]PI-2620 and [18F]PM-PBB3. Additionally, these two tracers and [18F]MK-6240 show promising results for imaging PSP- and CBD-tau. Overall, [18F]AV-1451 is the most widely studied tracer but the mixed results regarding its efficacy for use in imaging AP-tau is a cause for concern moving forward. Instead, future work may benefit from focusing on the second-generation radiotracers which seem to have a higher specificity for AP-tau than those originally developed for imaging AD-tau.
非典型帕金森综合征（APs）是一组与tau蛋白病理改变相关的疾病。这些疾病包括进行性核上性麻痹（PSP）和皮质基底节变性（CBD）。在疾病初期，这些非典型帕金森综合征可能具有与帕金森病（PD）及其他帕金森综合征相似的临床表现：运动迟缓、姿势不稳、震颤和认知功能下降。正因如此，准确早期诊断非典型帕金森综合征是一个主要障碍。正电子发射断层扫描（PET）放射性示踪剂研发的最新进展使得在阿尔茨海默病（AD）中能够靶向病理性tau蛋白。目前，仍在进行相关工作以确定用于非典型帕金森综合征tau蛋白成像的首个同类放射性示踪剂。在本综述中，我们评估了有关当前tau蛋白PET放射性示踪剂在非典型帕金森综合征中体外和体内测试的文献。所评估的tau蛋白PET示踪剂包括第一代示踪剂（[18F]AV - 1451、[18F]FDDNP、[18F]THK衍生物和[11C]PBB3）以及第二代示踪剂（[18F]PM - PBB3、[18F]PI - 2620、[18F]RO - 948、[18F]JNJ - 067、[18F]MK - 6240和[18F]CBD - 2115）。第一代示踪剂与脑白质和基底节的脱靶结合问题仍然突出，但在少数第二代示踪剂中似乎已得到缓解，包括[18F]PI - 2620和[18F]PM - PBB3。此外，这两种示踪剂以及[18F]MK - 6240在PSP和CBD - tau成像方面显示出有前景的结果。总体而言，[18F]AV - 1451是研究最广泛的示踪剂，但其用于非典型帕金森综合征tau蛋白成像的效果存在混合结果，这令人担忧。相反，未来的工作可能会受益于专注于第二代放射性示踪剂，它们似乎对非典型帕金森综合征tau蛋白具有比最初用于AD - tau成像的示踪剂更高的特异性。
