[Radiosensitizing effect of a 2-nitroimidazole hydroxamate (KIN-804) to murine tumors].
We studied the toxicity, pharmacokinesis and radiosensitizing effect of a newly developed 2-nitroimidazole-1-methylacetohydroxamate (KIN-804) in C3H/He mice bearing SCC-VII tumor. They were compared with misonidazole. LD50/7 of KIN-804 and misonidazole were 3200 and 2000 mg/kg. The concentration of KIN-804 in the brain and sciatic nerve was at a very low level and its clearance from the sciatic nerve was rapid. Enhancement ratios calculated using the growth delay method were 1.50 for KIN-804 and 1.36 for misonidazole respectively when they were administered by intraperitoneal injection with a dose of 100 mg/kg. KIN-804 was considered to be a promising radiosensitizer because it obtained less toxicity and a higher radiosensitizing activity than misonidazole.
Tada
T
T
Department of Radiology, Osaka City University Medical School.
Nakajima
T
T
Onoyama
Y
Y
Nagasawa
H
H
Hori
H
H
Inayama
S
S
D000818:Animals; D006877:Hydroxamic Acids / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D009593:Nitroimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity
D006877:Hydroxamic Acids; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C076264:2-nitroimidazole-1-methylacetohydroxamate