Radiation Biology of EPR Oxygen Images

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DESCRIPTION (provided by applicant): A new modality has been developed for imaging oxygen concentrations in living tissue. Electron Paramagnetic Resonance (EPR) Imaging (EPRI) has benefited by the development of novel spin probes by Nycomed Innovations (Malmo, SW). These probes have EPR spectra have a simple single line and that are nearly an order of magnitude narrower than most previously available spin probes. New spectral modeling algorithms allow the accurate extraction of spectral information from more intense, but distorted spectra. Injecting the spin probes iv, we have been able to derive oxygen images from FSa tumors in the legs of C3H mice with spatial resolution of 0.6 mm and oxygen resolution of 3.5 torr, obtained in 20 minutes. This work of this grant will test the relevance of these oxygen images to radiation biology. Despite the excellent data correlating radiation curability with pO2 as measured by Eppendorf electrodes, any new technique to measure oxygen must be correlated with radiation effect and well-established radiobiologic hypoxic parameters. Three specific aims will test 1) the extent to which summary parameters from EPRI oxygen images obtained in mice subject to artificial oxygenation manipulation quantitatively correlate with TCD50s in tourniquet induced hypoxia, carbogen breathing and carbogen breathing plus 1 g/kg glucose infusion, 2) the correlation of the EPRI oxygen image with Oxylite pO2 sampling, individual tumor paired survival assay, the comet assay, pimonidazole retention and the presence of hypoxia proteins 3) the ability of the EPRI oxygen image to distinguish subgroups among mouse tumors with different oxygenation to correlate with different mouse survival in mice treated to an overall TCD50. The studies correlating with other measures of hypoxia have been designed to spatially correlate the measurements with EPRI oxygenation maps, using a novel needle or trochar locating device to be used with the tumor in its imaging jig. These studies will investigate and validate this noninvasive oxygen imaging technology that provides a wealth of new information concerning oxygen distributions in tumors and normal tissues.