Precise Evaluation of Striatal Oxidative Stress Corrected for Severity of Dopaminergic Neuronal Degeneration in Patients with Parkinson’s Disease: A Study with 62Cu-ATSM PET and 123I-FP-CIT SPECT

Abstract

Background: This study sought to precisely evaluate striatal oxidative stress and its relationship with the disease severity in Parkinson’s disease (PD) using double brain imaging, ⁶²Cu-diacetyl-bis (N⁴-methylthiosemicarbazone) (⁶²Cu-ATSM) PET and ¹²³I-FP-CIT SPECT. Methods: Nine PD patients were studied with brain ⁶²Cu-ATSM PET for oxidative stress and ¹²³I-FP-CIT SPECT for the density of striatal dopamine transporter. Standardized uptake values (SUVs) were obtained from the delayed phase of dynamic ⁶²Cu-ATSM PET, and striatum-to-cerebellum SUV ratio (SUVR) was calculated. To correct the effect of neuronal loss in the striatum, ⁶²Cu-ATSM SUVR was corrected for striatal specific binding ratio (SBR) values of ¹²³I-FP-CIT (SUVR/SBR). Results: ⁶²Cu-ATSM SUVR without correction was not significantly correlated with disease severity estimated by the Unified Parkinson’s Disease Rating Scale (UPDRS) scores or ¹²³I-FP-CIT SBR. In contrast, the SUVR/SBR showed significant correlations with the UPDRS total and motor scores, and ¹²³I-FP-CIT SBR. Conclusion: Oxidative stress in the remaining striatal dopaminergic neurons estimated by SUVR/SBR was increased with disease severity in PD patients, suggesting that oxidative stress based on mitochondrial dysfunction contributes to promoting dopaminergic neuronal degeneration in PD. ⁶²Cu-ATSM PET with ¹²³I-FP-CIT SPECT correction would be a promising tool to evaluate dopaminergic neuronal oxidative stress in PD.