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  • Title: Radiation sensitization and chemopotentiation: RSU 1069, a compound more efficient than misonidazole in vitro and in vivo.
    Author: Adams GE, Ahmed I, Sheldon PW, Stratford IJ.
    Journal: Br J Cancer; 1984 May; 49(5):571-7. PubMed ID: 6547051.
    Abstract:
    Electron affinity as measured by the one-electron reduction potential, E17, is the major factor influencing radiosensitizing efficiency in vitro. RSU 1069 has an electron affinity (E17 = -398 mV) similar to misonidazole; however, the ability of this compound to sensitize hypoxic cells is considerably greater than that of misonidazole, e.g. 0.2 mM 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 g-1 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 mg g-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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