[Positron Emission Tomography Imaging for Oxidative Stress in Mitochondrial and Neurodegenerative Diseases]

Oxidative stress and mitochondrial dysfunction are assumed to be the pathogenic molecular mechanisms underlying various neurodegenerative diseases. We applied positron emission tomography (PET) with [⁶²Cu] diacetyl-bis (N⁴-methylthiosemicarbazone) (⁶²Cu-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 ⁶²Cu-ATSM uptake can be a promising biomarker for evaluating oxidative stress in patients with mitochondrial or neurodegenerative diseases. PET imaging with ⁶²Cu-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. ⁶²Cu-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.