Previous studies have indicated the effectiveness of the nitroimidazole derivatives metronidazole and Ro 07-0582 in specifically sensitizing the hypoxic cell fraction of solid tumors to single doses of ionizing radiation. A number of structural analogs of these compounds are only slightly water soluble but dissolve readily in dimethyl sulfoxide (DMSO). To determine the feasibility of testing such analogs in DMSO, the above compounds and a nitropyrrole were dissolved in DMSO and investigated using the KHT fibrosarcoma in C3H mice. Although DMSO by itself increases the D0 of the chronically hypoxic cells in the tumor, the addition of a known sensitizer results in sensitization relative to the DMSO hypoxic level which is similar to that observed for the drug in aqueous solution. This indicates that in vivo studies of structural analogs having low water solubility are possible, thus allowing a more comprehensive study to be made of the role of structural modification on the ability of compounds to act as radiosensitizers.

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