RADIOSENSITIZATION OF HYPOXIC MAMMALIAN-CELLS BY DINITROIMIDAZOLES

New compounds of the nitro- and dinitroimidazole series have been developed as radiosensitizers which selectively sensitize hypoxic mammalian cells to the lethal effect of ionizing radiation. Three compounds, 2,4(5)-dinitroimidazole, 2,4-dinitroimidazole-1-ethanol (KA161), and an imidazooxazole derivative, 2,3-dihydro-5-nitroimidazo-(2,1-b)oxazole (KA151), were tested for their ability to sensitize hypoxic Chinese hamster cells (V-79-753 B) in vitro. These agents were also tested for their toxicity by exposing the Chinese hamster cells at 20°C for 2 hr at various concentrations; the 2,4(5)-dinitroimidazole did not show toxicity up to 2 mM concentration, whereas its 1-hydroxyethyl analog and KA151 were toxic to these cells at concentrations of 1mM or higher. All the compounds were active sensitizers; 2,4-dinitroimidazole-1-ethanol (KA161) was the most effective radiosensitizer producing an enhancement ratio of 2.0 at 100 μM concentration and was found to be more efficient than misonidazole at this concentration. ESR studies of the radical anions indicated that KA161 also possessed a higher electron affinity than misonidazole.