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  • Title: In vivo radiosensitizing effect of nitroimidazole derivative KIN-804.
    Author: Tada T, Nakajima T, Onoyama Y, Murayama C, Mori T, Nagasawa H, Hori H, Inayama S.
    Journal: Int J Radiat Oncol Biol Phys; 1994 Jun 15; 29(3):601-5. PubMed ID: 8005823.
    Abstract:
    PURPOSE: In vivo characteristics of 2-nitroimidazole-1-methylacetohydroxamate (KIN-804), which is a newly developed hypoxic cell radiosensitizer, are presented. METHODS AND MATERIALS: The toxicity, pharmacokinetics, and radiosensitizing effect of KIN-804 were studied by in vivo experiments using C3H/He mice bearing the SCC-VII tumor. Results were compared with misonidazole (MISO). RESULTS: LD50(7) of KIN-804 and MISO were 3200 mg/kg and 2000 mg/kg, respectively. The peak of concentrations of KIN-804 in the tumor occurred 20 min after intraperitoneal injection and reached about 62% of the maximum concentration in the blood. The concentrations in brain and sciatic nerve were very low and clearance from sciatic nerve was rapid. Enhancement ratios of KIN-804 calculated using the growth delay method were 1.22, 1.50 and 1.71 at doses of 50, 100, and 200 mg/kg, respectively, compared with 1.36 for MISO at a dose of 100 mg/kg. In the TCD50 assay, enhancement ratios at a dose of 200 mg/kg were 1.69 for KIN-804 and 1.52 for MISO, respectively. CONCLUSION: KIN-804 is a promising radiosensitizer since it shows less toxicity and higher radiosensitizing activity than MISO.
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