Tada T
Department of Radiology, Osaka-Prefectural Habikino Hospital.
Nihon Igaku Hoshasen Gakkai Zasshi. 1995 Jan;55(1):70-5.
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.
KIN - 804（2 - 硝基咪唑 - 1 - 甲基乙酰氧肟酸）是日本研发的一种新型乏氧细胞放射增敏剂。在体外实验中它表现出高水平的放射增敏效果，并且因其亲水性侧链有望具有低神经毒性。本文对KIN - 804的体内特性进行了研究。使用C3H/He小鼠和SCC VII癌研究了急性毒性、药代动力学和放射增敏效果。米索硝唑用作标准对照。采用LD50/7评估急性毒性。KIN - 804和米索硝唑的LD50/7分别为3200 mg/kg和2000 mg/kg。使用高效液相色谱研究药代动力学。KIN - 804在肿瘤中的浓度在给药后20分钟达到峰值，达到血液中最大浓度的62%。在脑和坐骨神经中的浓度较低。采用生长延迟法评估放射增敏效果。KIN - 804在剂量为200、100和50 mg/kg时的增敏比分别为1.71、1.50和1.22，而米索硝唑在剂量为100 mg/kg时的增敏比为1.36。当进行分次照射时，KIN - 804在剂量为100 mg/kg时的增敏比降至1.25。基于这些结果，KIN - 804被认为是一种有前景的放射增敏剂。
