Demonstration of radiosensitization of hypoxic cells in solid tumours by metronidazole

Abstract

Significant radiosensitization of naturally occurring hypoxic cells by metronidazole (“Flagyl”) is demonstrated in two contrasting types of solid murine tumours, and at concentrations producing little toxicity. In first-generation transplanted mammary carcinomas in C³H mice the X-ray dose required to control half the irradiated tumours at 150 days was reduced by a factor of 1·36. In a fast-growing serially-transplanted sarcoma “F” in CBA mice the enhancement ratio, estimated from rates of loss of ¹²⁵IUdR from the tumours in vivo was also at least 1·3. The peak serum concentrations of metronidazole during the irradiation were 480 and 460 μg/ml. respectively. These are high concentrations and future work with hypoxic cell sensitizers should aim at achieving effective sensitization for smaller amounts of drug administered.