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Summary.-Tumour experiments including local control after X-irradiation have been performed, using a new technique that eliminates the need for anaesthetics in restraining the animals. This system has been used to investigate the degree of sensitization that can be achieved with ICRF 159 and 4 strongly electron-affinic radiosensitizers, nifurpipone dihydrochloride, metronidazole, Ro-11-3696 and Ro-07-0582.No significant enhancement of the radiation effect was observed with ICRF 159. Significant sensitization was achieved by all 4 nitro-heterocyclic compounds, Ro-07-0582 being the most effective, metronidazole and Ro-11-3696 the next, and nifurpipone dihydrochloride the least effective.For Ro-07-0582 and metronidazole, several drug concentrations were investigated, and the interval between injection with Ro-07-0582 and irradiation was varied: an interval of 30 min gave more sensitization than an interval of 90 min.The results from the local control experiments using Ro-07-0582 have been compared with those obtained from regrowth delay experiments. The radiosensitization obtained by the Ro-07-0582 increased with the X-ray dose above 25 gray.Both metronidazole and Ro-07-0582 gave significant enhancement of effect at serum concentrations which can be achieved in man.

Summary Electron affinity as measured by the one-electron reduction potential, E7,, is the major factor influencing radiosensitizing efficiency in vitro. RSU 1069 has an electron affinity (E1 -398 mV) similar to misonidazole; however, the ability of this compound to sensitize hypoxic cells is considerably greater thdn that of misonidazole, e.g. 0.2mM RSU 1069 gives an enhancement ratio of 2.2 compared to 1.5 for the same concentration of misonidazole. Radiosensitization studies with the MT tumour in vivo also showed RSU 1069 to be a more efficient sensitizer than misonidazole. An administered dose of only 0.08 mg g1 RSU 1069 yielded an enhancement of 1.8 to 1.9 using tumour cell survival and tumour cure as end-points.The ability of RSU 1069 to potentiate the cytotoxic action of melphalan towards the MT tumour was also examined. RSU 1069 (0.08 mgg -1) given to mice 1 h before melphalan resulted in an enhancement of 3.0. In contrast, previous studies had shown with a series of nitroimidazoles including misonidazole that Ro 03-8799 was the most effective potentiating agent, but this only gave an enhancement of 2.3 at a 10-fold higher dose than RSU 1069.RSU 1069 is a compound of substantial promise both as a radiosensitizer and chemopotentiating agent and warrants further investigation.

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