Tumor oxygenation was measured in the rat 13762 mammary carcinoma over a time course from 30 min to 3 days after hyperthermia treatment of 43 degrees C, 30 min or 40 degrees C, 80 min, while the animals breathed air, carbogen or after administration of a perflubron emulsion with air or carbogen breathing. Shortly (30 min and 3 h) after treatment with 43 degrees C, 30 min, the 13762 tumors were more hypoxic, as determined by the percent of pO(2) readings <5 mmHg and median pO(2), than prior to treatment and by 24 h had returned to initial oxygenation. Administration of the perflubron emulsion and carbogen breathing abrogated the increase in hypoxia and improved tumor oxygenation. Athymic mice bearing the DU-145 human prostate carcinoma were treated with hyperthermia regimens 40 degrees C, 41 degrees C, 42 degrees C or 43 degrees C for 60 min and tumor oxygenation was then measured over a time course while the animals breathed air or carbogen. Shortly (30 min) after hyperthermia, the DU-145 tumors were more hypoxic than initially when the animals breathed air. Three days later, the DU-145 tumors treated with 41 degrees C: 42 degrees C or 43 degrees C remained hypoxic but the tumors treated with 40 degrees C were better oxygenated than initially. When the animals bearing the DU-145 tumor breathed carbogen during the tumor oxygenation measurements only tumors treated with 43 degrees C were more hypoxic shortly after hyperthermia treatment. Three days after hyperthermia, the DU-145 tumors treated with 40 degrees C and 43 degrees C were better oxygenated than initially while those treated with 41 degrees C and 42 degrees C were less oxygenated when the animals breathed carbogen during the oxygen measurements. Thus, the effect of hyperthermia on tumor physiology can persist for days post treatment and vary with the temperature of the treatment.

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