Tumor oxygen status is an important factor in the choice of therapeutic regimen. Hypoxic tumors are more resistant to radiation alone. Thus, a number of adjuvant treatments have been designed to increase tissue oxygenation (pO2) in radio resistant tumor regions. A priori knowledge of tumor pO2 will significantly influence the choice of cancer treatment using radiation. Currently used pO2 measurements in clinical oncology are invasive and insensitive, yet produce useful information and provide guidance to select efficacious treatment regimens. However, invasive nature of the procedure limits such measurements to accessible tumors or in patients willing to undergo invasive measurements. Electron paramagnetic resonance (EPR) spectroscopy and imaging (EPRI) are capable of performing noninvasive physiological measurements in living objects. EPRI is a functional imaging modality, similar to MRI, yet sensitive in providing accurate spatial maps of hypoxic zones, non- invasively. We have previously used these techniques to measure tumor morphology, redox state and oxygenation in experimental tumor models. We have recently developed new EPR probes for oximetry that are chemically and biologically inert, but whose spectral properties are highly sensitive to oxygen, particularly in the tumor hypoxic range. These probes can be infused into the vasculature or chronically implanted at sites of interest, thus making it possible to obtain pO2 information repeatedly after treatment with ionizing radiation, chemotherapy or agents, which alter systemic blood pressure and oxygenation. A proper knowledge of the influence of such manipulations on tumor physiology should provide new avenues to explore in modifying/enhancing the therapeutic effects of ionizing radiation. The goal of the present proposal is to extend the capabilities of in vivo EPR spectroscopy and imaging to accurately measure and map oxygen concentration and blood perfusion in tumors under a variety of conditions including pharmacological modifications of tumor vasculature, blood flow, oxygenation and post- irradiation changes. These measurements will be compared and complemented with other techniques including MRI and fiber-optic methods in measuring tissue oxygenation. Information obtained from these studies should enable the development and optimization of therapeutic modalities for cancer treatment.
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