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  • Title: [Radiosensitizer: hypoxic cell radiosensitizer].
    Author: Mori T.
    Journal: Gan To Kagaku Ryoho; 1989 Apr; 16(4 Pt 2-2):1399-404. PubMed ID: 2525001.
    Abstract:
    There is a world-wide demand for a clinically usable sensitizer for radio-resistant hypoxic cells. After unsuccessful clinical trials of misonidazole, many efforts have been made to develop new sensitizers. In the U.S., Brown and others reported a new drug named SR-2508 (ethanidazole), which is now in phase II and III clinical trials. In Japan, many drugs were synthesized and tested with the screening systems using EMT6 and SCCVII tumor. Since the failure with misonidazole is due to its neurotoxicity, two methods have been applied to find new sensitizers. The first one is to increase the sensitizing effects and the other is to decrease the neurotoxicity. KU-2285 is fluorinated nitroimidazole, and it has a higher sensitizing effect than misonidazole or SR-2508. Its sensitizing effect is 1.65 at 200 mg/kg, and the LD50 value is 2.3 g/kg. Hoping for less neurotoxicity, RK-28, RP-170 and KIH-801 were synthesized. RP-170 demonstrated less toxicity than Miso, and KIH-801 demonstrated an unexpectedly high sensitizing effect especially is in vivo experiments. Although RK-28 has a low LD50 value, it shows rapid clearance rate from serum and is supposed to have less cumulative neurotoxicity. KU-2285, RK-28, RP-170 and KIH-801 all await further clinical trials.
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