PET Imaging with [¹⁸F]ROStrace Detects Oxidative Stress and Predicts Parkinson's Disease Progression in Mice

• Main Authors: Yi Zhu (Author), Neha Kohli (Author), Anthony Young (Author), Malkah Sheldon (Author), Jani Coni (Author), Meera Rajasekaran (Author), Lozen Robinson (Author), Rea Chroneos (Author), Shaipreeah Riley (Author), Joseph W. Guarnieri (Author), Joshua Jose (Author), Nisha Patel (Author), Douglas C. Wallace (Author), Shihong Li (Author), Hsiaoju Lee (Author), Robert H. Mach (Author), Meagan J. McManus (Author)
• Format: Book
• Published: MDPI AG, 2024-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Although the precise molecular mechanisms responsible for neuronal death and motor dysfunction in late-onset Parkinson's disease (PD) are unknown, evidence suggests that mitochondrial dysfunction and neuroinflammation occur early, leading to a collective increase in reactive oxygen species (ROS) production and oxidative stress. However, the lack of methods for tracking oxidative stress in the living brain has precluded its use as a potential biomarker. The goal of the current study is to address this need through the evaluation of the first superoxide (O₂^•−)-sensitive radioactive tracer, [¹⁸F]ROStrace, in a model of late-onset PD. To achieve this goal, MitoPark mice with a dopaminergic (DA) neuron-specific deletion of transcription factor A mitochondrial (<i>Tfam</i>) were imaged with [¹⁸F]ROStrace from the prodromal phase to the end-stage of PD-like disease. Our data demonstrate [¹⁸F]ROStrace was sensitive to increased oxidative stress during the early stages of PD-like pathology in MitoPark mice, which persisted throughout the disease course. Similarly to PD patients, MitoPark males had the most severe parkinsonian symptoms and metabolic impairment. [¹⁸F]ROStrace retention was also highest in MitoPark males, suggesting oxidative stress as a potential mechanism underlying the male sex bias of PD. Furthermore, [¹⁸F]ROStrace may provide a method to identify patients at risk of Parkinson's before irreparable neurodegeneration occurs and enhance clinical trial design by identifying patients most likely to benefit from antioxidant therapies.

Item Description

10.3390/antiox13101226
2076-3921