The optimal combination of hyperthermia and carbogen breathing to increase tumor oxygenation and radiation response

Purpose: To determine the most effective combination of carbogen breathing with mild temperature hyperthermia (MTH) to increase the oxygenation and radiation response in murine tumors, Methods and Materials: MTH at 41,5 degrees C for 60 min was applied by immersion of the tumor in a precisely controlled water bath. The tumor pO(2) was measured with a polarographic microelectrode. The radiation response of the tumor was determined using the in vivolin vitro assay for surviving tumor cells. Results: In the FSaII fibrosarcoma the median pO(2) increased from a control value of 6.5 +/- 0.5 mm Hg to 16.6 +/- 1.1 mm Hg immediately after MTH and was 10.9 +/- 1.3 mm Hg 24 h later. Carbogen breathing for 5 min increased the FSaII pO(2) to 19.9 +/- 2.1 mm Hg. Carbogen breathing for 5 min beginning immediately after MTH increased the median pO(2) more than 5 times to 35.4 +/- 3.8 mm Hg. This combined treatment also substantially increased the response of the tumors to a radiation exposure of 20 Gy, In another tumor model, the SCK mammary carcinoma, MTH treatment increased the median pO(2) from the control level of 4.4 +/- 0.2 mm Hg to 12.6 +/- 1.2 mm Hg, and it returned to 4.3 +/- 0.3 mm Hg 24 h later, Carbogen breathing for 5 min increased the SCK tumor pO(2) to 17.1 +/- 1.4 mm Hg. The median SCK pO(2) was increased about 7 times to 31.2 +/- 4.2 mm Hg when MTH was followed immediately with carbogen breathing for 5 min. The radiation response was also markedly increased by this combination, When the animals breathed carbogen for 15 or 30 min, the pO(2) and radiosensitivity in both tumor types either remained the same or was lower than that after 5 min of breathing, In addition, both FSaII and SCK tumors were radiosensitized 24 h after MTH treatment alone or with 5 min of carbogen breathing. Conclusions: A shorter carbogen breathing time immediately after MTH causes the most tumor radiosensitization, The results of this study also demonstrate that MTH increases radiosensitivity with and without carbogen breathing up to 24 h after the mild hyperthermia treatment. (C) 1998 Elsevier Science Inc.