Interaction of misonidazole, hyperthermia, and irradiation in a C3H mammary carcinoma and its surrounding skin in vivo

Abstract The interaction of irradiation, Misonidazole (MISO), and hyperthermia was studied in a C3H mouse mammary carcinoma and its surrounding skin in vivo . MISO (0.5–1.0 mg/g) was injected 30 min before irradiation. Hyperthermia (41.5°–43.5°C for 60 min) was given either simultaneously, 0.5 hr, or 4 hr after X rays. The results were evaluated as the radiation dose to achieve tumor control (TCD 50 ) or moist desquamation of the skin (DD 50 ) in half of the treated animals. A therapeutic gain was found when the enhancement in tumors were greater than that found in skin. The combination of simultaneous heat and irradiation caused great enhancement in radiation response, but with no therapeutic gain. A slightly lower enhancement of the damage in both tissues was found with a 30 min interval between irradiation and hyperthermia, whereas heat 4 hr after X rays gave a small, but significant therapeutic gain. MISO significantly enhanced the response in tumors but not in skin. Combined trimodality treatment with MISO, irradiation, and hyperthermia resulted in enhancement ratios up to 15, dependent on temperature, radiation-heat interval, and to a lesser extent the MISO dose. The enhancement was for all schedules most pronounced in the tumors, resulting in an improved therapeutic effect. The combination of MISO and hyperthermia may be a valuable addition to radiotherapy, especially if heat and irradiation can be applied with close interval and with one of the modalities given selectively to the tumor.