In vivo radiosensitizing effect of nitroimidazole derivative KIN-804.

In vivo characteristics of 2-nitroimidazole-1-methylacetohydroxamate (KIN-804), which is a newly developed hypoxic cell radiosensitizer, are presented.
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).
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.
KIN-804 is a promising radiosensitizer since it shows less toxicity and higher radiosensitizing activity than MISO.
AuthorsT Tada, T Nakajima, Y Onoyama, C Murayama, T Mori, H Nagasawa, H Hori, S Inayama
JournalInternational journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 29 Issue 3 Pg. 601-5 (Jun 15 1994) ISSN: 0360-3016 [Print] UNITED STATES
PMID8005823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hydroxamic Acids
  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • 2-nitroimidazole-1-methylacetohydroxamate
  • Misonidazole
  • Animals
  • Carcinoma, Squamous Cell (pathology, radiotherapy)
  • Dose-Response Relationship, Drug
  • Hydroxamic Acids (pharmacokinetics, pharmacology, toxicity)
  • Lethal Dose 50
  • Mice
  • Mice, Inbred C3H
  • Misonidazole (pharmacology)
  • Nitroimidazoles (pharmacokinetics, pharmacology, toxicity)
  • Radiation-Sensitizing Agents (pharmacology)

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