In vivo radiosensitizing effect of nitroimidazole derivative KIN-804

Journal Article · Wed Jun 15 00:00:00 EDT 1994 · International Journal of Radiation Oncology, Biology and Physics; (United States)

DOI:https://doi.org/10.1016/0360-3016(94)90465-0· OSTI ID:6946340

Tada, Takuhito ^[1]; Nakajima, Toshifumi; Onoyama, Yasuto ^[2]; Murayama, Chieko; Mori, Yomoyuki ^[3]; Nagasawa, Hideko ^[4]; Hori, Hitoshi ^[5]; Inayama, Seiichi ^[6]

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1. Osaka-Prefectural Habikino Hospital, Habikino-City (Japan) Osaka City Univ. Medical School (Japan)
2. Osaka City Univ. Medical School (Japan)
3. Tokai Univ. School of Medicine (Japan)
4. Keio Univ., Tokyo (Japan)
5. Tokushima Univ. (Japan)
6. Keio Univ., Tokyo (Japan) Tokushima Univ. (Japan)

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 SCCVII tumor. Results were compared with misonidazole (MISO). LD[sub 50]7 of KIN-804 and MISO were 3200 mg/kg and 2000 mg/kg, respectively. The peak concentration 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 TCD[sub 50] 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. 10 refs., 5 figs.

• OSTI ID: 6946340
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (United States), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (United States) Vol. 29:3; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
560300 -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AZOLES
COMPARATIVE EVALUATIONS
DRUGS
EVALUATION
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOSENSITIVITY
RADIOSENSITIZERS
TOXICITY