title: [Radiosensitizing effects of nitroimidazole derivative, KIN-804].
abstract: KIN-804(2-nitroimidazole-1-methylacetohydroxamate) is a new hypoxic cell radiosensitizer developed in Japan. It showed a high level of radiosensitizing effect in vitro experiments and is expected to have low neurotoxicity because of its hydrophilic side chain. In this paper, the in vivo characteristics of KIN-804 were studied. Acute toxicity, pharmacokinetics and radiosensitizing effect were studied using C3H/He mice and SCC VII carcinoma. Misonidazole was used as a standard comparison. LD50/7 was used for the evaluation of acute toxicity. The LD50/7 of KIN-804 and Misonidazole were 3200 mg/kg and 2000 mg/kg, respectively. Pharmacokinetics were studied using high performance liquid chromatography. The concentration of KIN-804 in the tumor peaked 20 min after administration and reached 62% of the maximum concentration in blood. The concentrations in brain and sciatic nerve were low. The radiosensitizing effect was evaluated using the growth delay method. The enhancement ratios of KIN-804 were 1.71, 1.50 and 1.22 at doses of 200, 100 and 50 mg/kg, respectively, compared with 1.36 for Misonidazole at a dose of 100 mg/kg. When irradiation was performed with double fractionation, the enhancement ratio of KIN-804 at a dose of 100 mg/kg decreased to 1.25. Based on these results, KIN-804 is considered a promising radiosensitizer.
authors.affiliation: Department of Radiology, Osaka-Prefectural Habikino Hospital.
authors.forename: T
authors.initials: T
authors.lastname: Tada
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy*; D006877:Hydroxamic Acids / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000494:pharmacology; D009593:Nitroimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000532:radiotherapy*
chemical_list: D006877:Hydroxamic Acids; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C076264:2-nitroimidazole-1-methylacetohydroxamate; D008920:Misonidazole