Combining bioreductive drugs and radiation for the treatment of solid tumors

Correlation between the hypoxic toxicity of various nitroheterocycles toward Chinese hamster V79 cells and the 1-electron reduction potential of the compounds. The more electron-affinic compounds (ie, less negative reduction potential) showing the greater toxicity.  ̂, 2-nitroimidazoles; ●, 5-nitroimidazles; ▵, 5-nitrofurons.

Growth delay of the MT fibrosarcoma grown in WHT mice given graded doses of radiographs. X, radiation only;  ̂, mice given 1 mg/g misonidazole 30 minutes before irradiation; ●, ▵, mice given 1 mg/g misonidazole 5 minutes after irradiation. The group of mice illustrated by the open triangle were held at 37°C for 3.5 hours after treatment with Misonidazole. Upward arrows indicate cures in those groups.²⁶.

Mechanism of the reductive elimination of aspirin from a 2-nitroimidazole prodrug.⁶⁸.

Mechanism of the reductive elimination of an alkylating mustard from an indolequinone prodrug.⁶⁹.

Tumor-free survival data for HT1080 (EGFP-5 and R-9) xenografts treated with radiographs plus or minus 250 mg/kg RB6145.⁷⁷.