Radioprotection combined with hypoxic sensitization during radiotherapy of a solid murine tumor

EMT6 tumors were transplanted intramuscularly in the right hind leg of female BALB/c mice and irradiated when they reached a diameter of 6-7 mm. Each mouse received an intraperitoneal injection of WR-2721, misonidazole, or both prior to irradiation, and the dose needed to control half of the tumors at 30 days (TCD50/30) was recorded. WR-2721 offered slight tumor protection, with a dose-modifying factor (DMF) of 1.04-1.15 for radioprotector doses of 150-500 mg/kg. Pretreatment with misonidazole at doses of 300-900 mg/kg yielded tumor sensitization with a DMF of 0.71-0.92. Pretreatment with both WR-2721 and misonidazole gave overall tumor sensitization with a DMF of 0.78-0.97. Possible combinations of sensitizers and protectors, while providing overall tumor sensitization, do not seem to improve the therapeutic ratio over what could be obtained from a sensitizer or protector alone.