Radiosensitization of Hypoxic Mammalian Cells by Dinitroimidazoles

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Abstract
New compounds of the nitro- and dinitroimidazole series were developed as radiosensitizers which selectively sensitize hypoxic mammalian cells to the lethal effect of ionizing radiation [for use in radiotherapy]. 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 lung cells (V-79-753 B) in vitro. These agents were also tested for their toxicity by exposing the Chinese hamster cells at 20.degree. C for 2 h 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 1 mM 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 .mu.M concentration and was more efficient than misonidazole at this concentration. ESR studies of the radical anions indicated that KA161 also possessed a higher electron affinity than misonidazole.