Evaluation of striatal oxidative stress in patients with Parkinson's disease using [62Cu]ATSM PET

Abstract

Introduction: To clarify the role of oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson's disease (PD) in living patients, positron emission tomography (PET) with [(62)Cu]diacetyl-bis(N(4)-methylthiosemicarbazone) ([(62)Cu]ATSM) was applied to functional imaging of oxidative stress mainly due to mitochondrial dysfunction in the striata of patients with PD.

Methods: Fifteen PD patients who presented with lateral dominant symptoms at onset and six healthy controls underwent [(62)Cu]ATSM PET. 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 the 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<.05). In the patients, the S/C ratio of the bilateral striata showed a positive correlation with the Unified Parkinson's Disease Rating Scale (UPDRS) rating (r=0.52, P<.05), and the S/C ratio of the striatum contralateral to the initially affected body side showed a strong positive correlation with the UPDRS rating (r=0.62, P<.05).

Conclusions: [(62)Cu]ATSM PET imaging demonstrated that striatal oxidative stress was enhanced in PD patients compared with the controls and increased with the progression of disease severity, particularly in the contralateral striatum. These findings indicated that oxidative stress associates with striatal neurodegeneration in PD.