PET Imaging of Striatal Oxidative Stress in Patients with Parkinson's Disease Using 62Cu-ATSM (S22.002)

Abstract

Objective: To evaluate oxidative stress in the striatum of living patients with Parkinson9s disease (PD) using positron emission tomography (PET) with [ 62 Cu]diacetyl-bis( N 4 -methylthiosemicarbazone) ( 62 Cu-ATSM). Background The effects of oxidative stress and mitochondrial dysfunction on neurodegeneration in the pathogenesis of PD in living patients remain unknown. High-level accumulation of 62 Cu-ATSM indicates an over-reduction state mainly caused by mitochondrial dysfunction, which leads to oxidative stress (Yoshii Y, et al. Nucl Med Biol 2011). Thus, 62 Cu-ATSM PET allows regional oxidative stress mainly due to mitochondrial dysfunction to be imaged in the brains of living patients (Ikawa M, et al. Mitochondrion 2009). Design/Methods: Fifteen PD patients who presented with lateral dominant symptoms at onset and six healthy controls underwent 62 Cu-ATSM PET. The severity of symptoms was evaluated employing the Unified Parkinson9s Disease Rating Scale (UPDRS). Dynamic PET data acquisition was performed, and standardized uptake values (SUVs) were obtained from the delayed phase of dynamic data by means of region of interest analysis. The striatum-to-cerebellum SUV ratio (S/C ratio) was calculated from the SUV in all subjects of the striatum and cerebellar cortex. Results: The mean S/C ratio of the bilateral striata of the patients (1.15±0.10) was significantly increased compared with that of the controls (1.08±0.02) ( P r =0.52, P r =0.62, P Conclusions: 62 Cu-ATSM PET imaging demonstrated that striatal oxidative stress was enhanced in PD patients compared with the controls and increased with progression of the disease severity, particularly in the contralateral striatum. These findings indicate that oxidative stress associates with neurodegeneration in the nigrostriatal system in PD. Supported by: The National Institute of Radiological Sciences, Chiba, Japan. We wish to thank Dr. T. Fukumura of the Molecular Imaging Center, National Institute of Radiological Sciences, for synthesizing the 62 Cu-ATSM. This study was funded in part by Grants-in-Aid for Scientific Research (B) (17209040), Scientific Research on Innovative Areas (2020021) and Young Scientists (B) (21790838) from the Japan Society for the Promotion of Science and the 21st Century COE Program (Medical Science). Disclosure: Dr. Ikawa has nothing to disclose. Dr. Okazawa has nothing to disclose. Dr. Kudo has nothing to disclose. Dr. Nakamoto has nothing to disclose. Dr. Fujibayashi has nothing to disclose. Dr. Yoneda has nothing to disclose.