Positron Emission Tomography of Oxidative Stress in Neurodegenerative Diseases

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Neurodegenerative diseases are chronic, progressive, and terminal illnesses. Currently, there is little understanding of the pathological mechanisms that drive disease progression, there are no effective treatments, and there are no sensitive biometrics of illness progression for ANY neurodegenerative disease. Oxidative stress has been proposed as one candidate molecular process that may be associated with most, if not all, neurodegenerative diseases, either as a causal contributor to neuropathology, or as a marker of the cellular dysfunction underlying these diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Motor Neuron Disease, and Friedreich ataxia. Measuring and tracking oxidative stress in the human brain using Positron Emission Tomography (PET) and complimentary Magnetic Resonance Imaging (MRI) approaches provides opportunities for in vivo mechanistic characterisations disease in the human brain, and represents a novel and potentially sensitive approach to addressing the urgent need for pharmacodynamic and treatment monitoring biomarkers for use in clinical trials, with broad relevance to a large number of neurological illnesses. The current study aims to investigate 64Cu-ATSM PET as a tool for imaging oxidative stress in the brains of individuals with neurodegenerative illnesses. This work will allow us to determine the contribution of oxidative stress, measured in vivo, to the pathological sequelae of disease progression, opening a host of potential new opportunities for treatment and treatment monitoring, as well as disease characterization. This work will also serve to support the wider application of these research protocols to a broad range of neurological and psychiatric conditions.

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