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

• Published in: Antioxidants Vol. 13; no. 10; p. 1226
• Main Authors: Zhu, Yi, Kohli, Neha, Young, Anthony, Sheldon, Malkah, Coni, Jani, Rajasekaran, Meera, Robinson, Lozen, Chroneos, Rea, Riley, Shaipreeah, Guarnieri, Joseph W, Jose, Joshua, Patel, Nisha, Wallace, Douglas C, Li, Shihong, Lee, Hsiaoju, Mach, Robert H, McManus, Meagan J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.10.2024; MDPI
• Subjects: Basal ganglia; Central nervous system diseases; Dopamine receptors; Metabolic disorders; Metabolism; Mitochondria; Mitochondrial DNA; Molecular modelling; Movement disorders; Neurodegeneration; neurodegenerative disease; Neurodegenerative diseases; Neuroimaging; neuroinflammation; Neurons; Oxidative stress; Parkinson's disease; Pathogenesis; Positron emission tomography; positron emission tomography (PET); Reactive oxygen species; reactive oxygen species (ROS); Sensitivity analysis; Software; United States > US; neurodegenerative disease; neuroinflammation; positron emission tomography (PET); mitochondria; reactive oxygen species (ROS); oxidative stress; MitoPark mouse model
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox13101226

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 (O )-sensitive radioactive tracer, [ F]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 ( ) were imaged with [ F]ROStrace from the prodromal phase to the end-stage of PD-like disease. Our data demonstrate [ F]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. [ F]ROStrace retention was also highest in MitoPark males, suggesting oxidative stress as a potential mechanism underlying the male sex bias of PD. Furthermore, [ F]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.