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In vitro and in vivo radiosensitization by 2-nitroimidazoles more electron-affinic than misonidazole

Journal Article · · Int. J. Radiat. Oncol., Biol. Phys.; (United States)
A series of 5-substituted-methyl-2 nitroimidazoles, more electron-affinic than misonidazole (MISO), has been studied as potential hypoxic cell radiosensitizers. In vitro radiosensitization studies of these compounds showed equivalent or greater radiosensitization than MISO, while LD/sub 50/ studies of the compounds found them to be, in general, more toxic to Balb/c mice than MISO. Radiosensitization experiments in vivo with compounds SR-2537, SR-2515 and SR-2553 of acceptable toxicity were not able to sensitize the EMT6 tumor to x-irradiation after a single intraperitoneal injection. However, moderate sensitization was achieved when SR-2537 was administered i.v. Rapid metabolism of these more electron-affinic compounds was suggested as a possible case of the poor sensitization. However, when multiple i.v. injections of SR-2537 were given to maintain a constant drug level in the tumor, radiosensitization by this compound did not improve, suggesting that intact drug was either not reaching or was not penetrating the hypoxic cells.
OSTI ID:
7065978
Journal Information:
Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8:3/4; ISSN IOBPD
Country of Publication:
United States
Language:
English