Radiosensitization of hypoxic cells in vivo by SR 2508 at low radiation doses: a preliminary report

The RIF-1 tumor implanted intradermally in the lower dorsum of C3H mice has been used to explore to what extent the radiosensitizer SR 2508 is capable of sensitizing hypoxic cells at clinically relevant doses of 1 and 2 Gy per fraction. SR 2508 was injected 45 min prior to each radiation dose in fractionated regimens of 2 or 4 doses/day for up to 5 days given locally to the tumors, which were clamped to occlude the blood supply prior to each radiation exposure. The response of the tumor cells with and without clamping and with and without SR 2508 was determined by constructing multifraction cell survival curves using the in vivo-in vitro assay. The initial results demonstrate significant radiosensitization of artificially hypoxic tumor cells at 1 and 2 Gy/fraction by SR 2508 (1000 mg/kg). Using the ratio of the D0's of the exponential, multifraction survival curves, an SER for SR 2508 of 1.6 or 5 obtained compared to an OER of 2.3. These data suggest that SR 2508 (and presumably other electron-affinic sensitizers) can radiosensitize hypoxic cells at low radiation doses, and indicate that this and similar drugs may be useful in the radiotherapy of those tumors for which hypoxia limits curability