OXYGEN LEVELS AND RADIOSENSITIVITY IN TUMORS

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DESCRIPTION: Quantitative, real time measurements of the oxygen pressure in tumors in vivo and in vitro will be used to determine the degree of hypoxia and its relationship to radiation sensitivity. The measurements will compare three independent methods for measuring oxygen in tissue, focusing on a new optical technique, oxygen dependent quenching of phosphorescence. O2 levels and treatment induced alterations in these levels, oxygen pressure distributions (histograms) in the tissue, and two and three dimensional maps of these oxygen distributions in the tissue will all be measured. Three important hypotheses will be tested. 1.Phosphorescence measurements permit detection of small tumors by the abnormal distributions of blood and oxygen pressures which are present within the tumors. 2. Phosphorescence measurements make it possible to quantitate the oxygen distribution in tumors and to evaluate, in real time, the efficacy of interventions designed to alter these oxygen levels. 3. The oxygen pressure in the tissue is critically important to radiation therapy and increased oxygen pressure in the tumor increases the fraction of cells killed by a dose of radiation. Our research program will: A. Quantitate the oxygen pressure in the blood within tumors and the surrounding tissue during the growth and development of the tumors. B. Quantitate the oxygen dependence of tumor response to radiation therapy and its response to interventions designed to alter tumor metabolism and physiology. C. Extend the phosphorescence quenching measurements to three dimensions by optically sectioning using different wavelengths of excitation light, thereby improving resolution of the distribution of oxygen and blood in the vasculature. D. Evaluate new phosphors for oxygen measurement in biological materials, with emphasis on those which absorb and phosphoresce in the near infra red region of the spectrum. The Pd-tetrabenzoporphyrin structure is being chemically modified to provide phosphors which are water soluble and with calibrations insensitive to alterations in their environment (pH, ionic strength, albumin concentration). Phosphors will be selected which can be injected intravenously and then, after the oxygen measurements, are excreted by the kidney.