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Uptake and additivity of the radiosensitizing effects of Ro 03-8799 and SR-2508 in mammalian cells in vitro.

There is currently considerable interest in combining the two 2- nitroimidazole radiosensitisers, Ro 03–8799 and SR-2508. The weak, lipophilic base Ro 03–8799 and the neutral, hydrophilic compound SR-2508 are both efficient radiosensitisers, but the dose-limiting toxic effects of these two agents are clinically somewhat different. The dose-limiting effect for Ro 03–8799 is predominantly central neuropathy (Roberts et al, 1984; Saunders et al, 1984) and that for SR-2508 is predominantly peripheral neuropathy (Coleman et al, 1986). Thus, by combining these two radiosensitisers it should be possible to increase the effective sensitising concentration without increasing toxicity. The effect of combining these two radiosensitisers should be additive, providing the intracellular distributions of the compounds do not differ greatly. Combinations of two rather similar nitro-containing radiosensitisers have been studied previously (McNally et al, 1978), but the hydrophilic and prototropic characteristics of SR-250...