Tests of Two Electron-Affinic Radiosensitizers in Vivo Using Regrowth of an Experimental Carcinoma

Two electron-affinic nitroimidazoles have been investigated as potential radiosensitizers using tumor regrowth as a measure of response. Both drugs, metronidazole, (May and Baker), and Ro-07-0582, (Roche), were effective radiosensitizers of hypoxic tumor cells. These sensitizers have previously been shown to be specific in that they are effective only on hypoxic cells and give no sensitization of well-oxygenated cells. Flagyl (metronidazole) gave an enhancement ratio of about 1.6 at 0.75 mg/g body weight. Ro-07-0582 sensitized both naturally occurring hypoxic cells in air-breathing mice, and acutely hypoxic cells in clamped tumors. It had a small effect when administered after irradiation with 2000 rads, and caused very slight slowing of tumor growth in unirradiated mice. Ro-07-0582 is the most effective sensitizer so far tested, giving an enhancement ratio of up to 2.1 when 1 mg/g is administered intraperitoneally. Since no enhancement of well-oxygenated normal tissue has been observed, this could correspond to a therapeutic gain factor of 2.1.