Harada Ryuichi, Okamura Nobuyuki
Department of Pharmacology, Tohoku University Graduate School of Medicine.
Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University.
Nihon Yakurigaku Zasshi. 2023;158(1):26-29. doi: 10.1254/fpj.22091.
Glial cells are non-neuronal cells that make up the central nervous system, including astrocytes, oligodendrocytes, microglia, and ependymal cells, which play an important role in brain homeostasis. However, activated microglia and reactive astrocytes cause neuroinflammation, which is closely related to neurodegeneration. Neuronal loss, gliosis, and accumulation of misfolded proteins are commonly observed in the brain of many neurodegenerative diseases at autopsy. Therefore, in vivo imaging of glial cell responses by positron emission tomography (PET) would be useful not only for understanding pathological processes, but also for differential diagnosis and evaluation of disease-modifying therapeutics targeting glial cells. The gold standard marker for reactive astrocytes is glial fibrillary acidic protein (GFAP), but no specific ligands are available. To date, there are two targets of reactive astrocytes that are under intense investigation: Monoamine oxidase-B (MAO-B) and imidazoline binding site (IBS). PET radiopharmaceuticals for MAO-B and IBS have been developed and are under clinical investigation. In this chapter, we review the MAO-B and IBS as molecular targets for imaging reactive astrocytes and introduce the PET tracers and their clinical studies.
神经胶质细胞是构成中枢神经系统的非神经元细胞，包括星形胶质细胞、少突胶质细胞、小胶质细胞和室管膜细胞，它们在脑内环境稳定中发挥着重要作用。然而，活化的小胶质细胞和反应性星形胶质细胞会引发神经炎症，这与神经退行性变密切相关。在许多神经退行性疾病患者死后的大脑中，常可观察到神经元丢失、胶质细胞增生以及错误折叠蛋白的积累。因此，通过正电子发射断层扫描（PET）对神经胶质细胞反应进行体内成像，不仅有助于理解病理过程，还可用于针对神经胶质细胞的疾病修饰疗法的鉴别诊断和评估。反应性星形胶质细胞的金标准标志物是胶质纤维酸性蛋白（GFAP），但目前尚无特异性配体。迄今为止，有两个针对反应性星形胶质细胞的靶点正在深入研究中：单胺氧化酶B（MAO-B）和咪唑啉结合位点（IBS）。用于MAO-B和IBS的PET放射性药物已研发出来并正在进行临床研究。在本章中，我们将综述MAO-B和IBS作为成像反应性星形胶质细胞的分子靶点，并介绍PET示踪剂及其临床研究。
