Preclinical Electron Paramagnetic Resonance Tumor Imager

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Summary Revolutionary methods of acquiring electron paramagnetic resonance (EPR) spectra of free radicals create a paradigm shift in application of EPR to understanding the role of radicals in cancer and in other diseases. Hitherto impossible studies are now feasible. Molecular oxygen, pH, local viscosity, distribution of probes, and general redox status of tissues are crucial parameters to understand tumors, determine targets for radiation and chemotherapy, and to monitor response to treatments. Lung damage, stroke, myocardial infarction, brain injury, wound healing, and other trauma, and peripheral vascular limitations may similarly benefit from EPR imaging of redox status. These physiologic parameters can be measured using nitroxide radicals, which are optimally detected with rapid scan EPR. Pulsed EPR measurement of local oxygen concentration with trityl radicals can guide radiation treatment of tumors in mice. The proposed system will include both of these powerful techniques. Experienced collaborators will test the imager in applications to redox equilibria in mouse tumors, reactive oxygen species related to cancer in mice, and acute lung injury. Space is at a premium in medical facilities, and in industry floor space for a new modality is expensive. Looking toward expanded use in the pharmaceutical industry the 1 GHz imager will be compact and transportable. Smaller, faster, more versatile imaging will enhance applications of oximetric imaging to tumor therapy and to the other pathologies listed above. The prototype with technology for both rapid scan spectroscopy and oximetric imaging will open new vistas for quantifying more physiologic parameters than oximetry alone. The integrated software system will enable use by technicians without advanced training in the underlying spectroscopy. The industrial partner, Bruker BioSpin, and University of Denver’s engineers will design a new generation of 1 GHz cross-loop and surface coil resonators, a small magnet and scan coils. Bruker contributes supplemental (optional) support beyond the grant budget with engineering team commitments to work on commercializing our rapid scan EPR method and components. Bruker brings to the team essential experience and know-how of commercial standards, manufacturability, long-term support, and customer needs. Lack of the proposed capability has stymied the expansion of EPR capabilities into more general biomedical research use. The innovation is the creation of a prototype that our team’s industrial component can refine into a marketable product with powerful EPR capability for end users.