IN-VIVO RADIOSENSITIZING EFFECT OF NITROIMIDAZOLE DERIVATIVE KIN-804

Purpose: In vivo characteristics of 2-nitroimidazole-1-methylacetohydr oxamate (KIN-804), which is a newly developed hypoxic cell radiosensit izer, are presented. Methods and Materials: The toxicity, pharmacokine tics, and radiosensitizing effect of KIN-804 were studied by in vivo e xperiments using C3H/Ne mice bearing the SCC-VII tumor. Results were c ompared with misonidazole (MISO). Results: LD(50)7 Of KIN-804 and MISO were 3200 mg/kg and 2000 mg/kg, respectively. The peak of concentrati ons of KIN-804 in the tumor occurred 20 min after intraperitoneal inje ction and reached about 62% of the maximum concentration in the blood. The concentrations in brain and sciatic nerve were very low and clear ance from sciatic nerve was rapid. Enhancement ratios of KIN-804 calcu lated 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 a t a dose of 100 mg/kg. In the TCD50 assay, enhancement ratios at a dos e 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.