Prospects for improved hypoxic cell radiation sensitizers

The neurotoxic properties of misonidazole will substantially limit its clinical applicability: sensitizers with higher therapeutic ratio are therefore required. This paper describes some of the steps that are being taken to achieve this. Therapeutic ratio can be increased by protection against the neurotoxic properties of misonidazole, increase of the sensitizing efficiency of this drug by different scheduling or by replacement of misonidazole by less neurotoxic and/or more efficient sensitizers. A split-dose scheme for the administration of misonidazole is proposed that could, in principle, exploit the fast component of radiosensitization and the additional sensitization that would be achieved by suppression of intracellular SH compounds. Properties of some sensitizers of current experimental or clinical interest are discussed. These include desmethylmisonidazole, less neurotoxic analogues of misonidazole, an unusually active series of nitroimidazoles and electronaffinic sensitizers containing alkylating functions. (author)