Ikawa Masamichi, Okazawa Hidehiko, Yoneda Makoto
Department of Advanced Medicine for Community Healthcare, Faculty of Medical Sciences, University of Fukui.
Brain Nerve. 2019 Feb;71(2):161-166. doi: 10.11477/mf.1416201236.
Oxidative stress and mitochondrial dysfunction are assumed to be the pathogenic molecular mechanisms underlying various neurodegenerative diseases. We applied positron emission tomography (PET) with [Cu] diacetyl-bis (N-methylthiosemicarbazone) (Cu-ATSM) to image cerebral oxidative stress based on mitochondrial dysfunction in living patients. In our previous study, we observed an increased retention of Cu-ATSM in in vitro cell lines with mitochondrial respiratory failure, suggesting that Cu-ATSM uptake can be a promising biomarker for evaluating oxidative stress in patients with mitochondrial or neurodegenerative diseases. PET imaging with Cu-ATSM successfully demonstrated the increased uptake in brain lesions of a patient with mitochondrial disease (MELAS), in the striatum of patients with Parkinson's disease, and in the motor cortex and motor-related cortices of patients with amyotrophic lateral sclerosis. The uptake for these disease-related brain regions strongly correlated with disease severity, indicating that oxidative stress based on mitochondrial dysfunction is associated with the neurodegenerative process in these diseases. Cu-ATSM PET imaging for oxidative stress has improved our insights into the pathological mechanisms of neurodegenerative diseases and may be a promising tool for monitoring further antioxidant and mitochondrial therapies.
氧化应激和线粒体功能障碍被认为是各种神经退行性疾病潜在的致病分子机制。我们应用正电子发射断层扫描（PET）结合[铜]双乙酰双（N-甲基硫代氨基脲）（Cu-ATSM），基于活体患者的线粒体功能障碍对脑氧化应激进行成像。在我们之前的研究中，我们观察到在体外线粒体呼吸衰竭的细胞系中Cu-ATSM的滞留增加，这表明Cu-ATSM摄取可能是评估线粒体或神经退行性疾病患者氧化应激的一个有前景的生物标志物。用Cu-ATSM进行PET成像成功地证明了线粒体疾病（MELAS）患者脑病变、帕金森病患者纹状体以及肌萎缩侧索硬化症患者运动皮层和运动相关皮层中摄取增加。这些与疾病相关的脑区的摄取与疾病严重程度密切相关，表明基于线粒体功能障碍的氧化应激与这些疾病的神经退行性过程有关。用于氧化应激的Cu-ATSM PET成像增进了我们对神经退行性疾病病理机制的理解，并且可能是监测进一步的抗氧化和线粒体治疗的一个有前景的工具。
