Analysis of tumor reoxygenation using ^<31>P-MRS and hypoxic cell imaging

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Tumor hypoxic status causes not only radioresistance but also malignant progression such as metastasis,tissue invasion of the tumor. Non-invasive measurement of tumor hypoxia is available for establishing individualization of the cancer treatment.(1) The amount of hypoxic fraction in a rodent tumor was evaluated by polarographic oxygen electrode, ^31P-MRS, and a newly synthesized hypoxic marker, β-D-IAZGP. We also investigated the relationship between the radiosensrtivity of the tumor and the hypoxic fraction predicted by these 3 methods. Radiosensitivity of the tumor was measured by in vivo/in vitro clonogenic assay. Tumor oxygenation status was also measured directly by polarographic oxygen electrodes and indirectly estimated by ^<31>P-MRS. Higher accumulaion of ^<123>I-β-D-IAZGP was observed in the tumors than that in normal tissues at 24hr after administration. As to biodistribution of ^<125>I-β-D-IAGP,the tumor/blood ratio varted widely, but it was correlated with tumor weight. Me … More an p_O_2 values and β-ATP/Pi, PCr/Pi ratios decreased significantly with the increase in tumor volume. As tumor volume increased, tumor cells became more resistant to radiation. The increase in tumor volume was significantly ccirelated with the recbction in mean p_O_2, decrease in ratios ofβATP/Pi or PCr/Pi, increase in uptake of β-D-IAZGP and redioresistance. Because the uptake of β-D-IAZGP can be measured non-invasively by nuclear medicine techniques, it could be clinically useful for monitoring hypoxia in human tumors.(2) To clarify a correlation between tumor hypoxia and malignant progression, we examined an expression of HIF-1 in the tumor of the stage III uterine cervix cancer. Five-year disease free survival rates were 41.2 % in HIF-1 positive group and 75.6% in HIF-1 negative group with statistical significance. Because strong correlation in distant metastasis was found between HIF-1 positive and negative group, the expression of HIF-1 showed malignant progression of the tumor in the uterine cervix. Less