There is strong evidence that high tumor oxygen levels predict the response of human tumors to radiation therapy and the hypothesis that post-irradiation reoxygenation contributes to the success of fractionated radiation. Methods for establishing the role of reoxygenation in the response to radiation of individual tumors, however, have not been available. EPR oximetry using implanted paramagnetic materials (PM) is capable of the repeated, sensitive pO2 assessments necessary to study reoxygenation in animal tumors and has the potential for clinical use. EPR has a high time resolution, is capable of spatial resolution and once the PM is implanted pO2 can be assessed non-invasively. In this project we are testing whether the changes in tumor pO2 occur after small, clinically relevant doses of radiation and whether reoxygenation assessed as tumor pO2 is predictive for improved tumor local control by ionizing radiation. Although reoxygenation has been shown to occur in virtually all animal tumor models, the mechanism have not been well worked out. Using EPR oximetry to determine the tumor dependent time course of post-irradiation pO2 we will examine systematically some of the factors that could contribute to reoxygenation. These include cell cycle changes and proliferation by flow cytometry, % necrotic fraction by histology, and dynamic imaging with MRI to assess tumor perfusion. If the overall goals of this project are realized it will improve the fundamental understanding of the role that oxygen plays in post-radiation reoxygenation in tumors.
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