18kDa转运蛋白(TSPO),以前被称为外周苯二氮卓受体,主要定位于类固醇生成细胞的线粒体外膜。在生理条件下脑TSPO表达相对较低,但响应神经胶质细胞激活而上调。作为神经炎症的主要指标,TSPO与许多神经精神疾病和神经退行性疾病的发病机制和进展有关。包括阿尔茨海默病(AD),肌萎缩侧索硬化(ALS),帕金森病(PD),多发性硬化症(MS),重度抑郁症(MDD)和强迫症(OCD)。在这种情况下,已经开发了许多TSPO靶向的正电子发射断层扫描(PET)示踪剂。其中,几种放射性配体已进入临床研究。在这次审查中,我们将概述TSPOPET示踪剂的最新发展,专注于放射性配体设计,放射性同位素标记,药代动力学,和PET成像评价。此外,我们会考虑目前的限制,以及TSPO放射性药物未来应用的翻译潜力。这篇综述旨在不仅提出当前TSPOPET成像中的挑战,同时也为TSPO靶向PET示踪剂的发现工作提供了新的视角。应对这些挑战将促进TSPO在与中枢神经系统疾病相关的神经炎症的临床研究中的翻译。
The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer\'s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson\'s disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.