Radiosensitization by Misonidazole (Ro 07-0582) The Importance of Timing and Tumor Concentration of Sensitizer

The radiosensitizing effect of misonidazole (Ro 07-0582) is presented for four types of mouse tumor. The interval between administration of the drug and irradiation has been found to have a large effect on the extent to which hypoxic tumor cells are sensitized. The optimal time for irradiation differed in the different tumors and ranged from 15 to 120 min. This delayed effectiveness probably relates to the time required for diffusion of the drug to the critical hypoxic regions and for its concentration in those regions to reach a maximum. Drug concentrations have been measured in whole blood and in the tumors using gas-liquid chromatography. The tumor concentrations ranged from 20 to 70% of the blood level in the four tumors; in man it was 40-107%. The in vivo radiosensitizing effect of the drug at these measured concentrations in tumors is similar to that achieved in vitro. The apparent loss in radiosensitizer effectiveness in mouse tumors in vivo relative to in vitro results is thus due to the lower con...