Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
ACS Chem Neurosci. 2021 Dec 15;12(24):4491-4499. doi: 10.1021/acschemneuro.1c00297. Epub 2021 Nov 23.
Mitochondrial dysfunction has been indicated in neurodegenerative and other disorders. The mitochondrial complex I (MC-I) of the electron transport chain (ETC) on the inner membrane is the electron entry point of the ETC and is essential for the production of reactive oxygen species. Based on a recently identified β-keto-amide type MC-I modulator from our laboratory, an F-labeled positron emission tomography (PET) tracer, , was prepared. PET/CT imaging studies demonstrated that exhibited rapid brain uptake without significant wash out during the 60 min scanning time. In addition, the binding of was higher in the regions of the brain stem, cerebellum, and midbrain. The uptake of can be significantly blocked by its parent compound. Collectively, the results strongly suggest successful development of MC-I PET tracers from this chemical scaffold that can be used in future mitochondrial dysfunction studies of the central nervous system.
线粒体功能障碍已在神经退行性疾病和其他疾病中得到证实。电子传递链（ETC）的线粒体内膜上的线粒体复合物 I（MC-I）是 ETC 的电子进入点，对活性氧的产生至关重要。基于我们实验室最近鉴定的一种β-酮酰胺型 MC-I 调节剂，制备了一种 F-标记的正电子发射断层扫描（PET）示踪剂 。PET/CT 成像研究表明，在 60 分钟的扫描时间内， 表现出快速的脑摄取，没有明显的洗脱。此外， 在脑干、小脑和中脑区域的结合更高。其母体化合物可显著阻断 的摄取。总的来说，这些结果强烈表明，可以从该化学支架中成功开发出用于中枢神经系统线粒体功能障碍研究的 MC-I PET 示踪剂。
