Functional PET Imaging of Oxidative Stress

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DESCRIPTION (provided by applicant): Molecular imaging agents targeting specific biomarkers are becoming more prevalent in an effort to enable personalized medicine. The cost to develop novel targeted imaging agents or therapeutics can be economically detrimental as many targeted agents will impact relatively small segments of the population. The Positron Emission Tomography (PET) agent 18F-fluorodeoxyglucose (18FDG) owes its success to the fact that it targets a ubiquitous mechanism, glucose uptake, required for increased cellular metabolism that has found wide clinical relevance from oncology to heart and brain function. We propose to develop a novel class of PET imaging agents, which are substrates for a molecular transporter that is ubiquitously activated as cells response to oxidative stress. In orde for this transport system to be utilized as a novel imaging biomarker, the transporter must have sufficient promiscuity to accept substrates with an appended label. Our team has already demonstrated this vital milestone of transporter promiscuity and demonstrated in vivo uptake of cystine in tumors validated for transporter activity. The goal of this proposal is to develop the best parent substrate and radiolabel combination for maximal transport efficiency and to demonstrate in vivo imaging of cellular oxidative stress. An oxidative stress PET imaging agent would have a potential broad utility for many of the indications that include cellular oxidative stress; including neurodegenerative diseases, atherosclerosis, ischemia, organ transplant rejection, autoimmune diseases, inflammatory diseases, oncology and aging.