A fluorinated 2-nitroimidazole, KU-2285, as a new hypoxic cell radiosensitizer
- Department of Radiology, Faculty of Medicine, Kyoto University (Japan)
To develop new hypoxic cell radiosensitizers, we incorporated fluorine atoms into the side chain of the 2-nitroimidazole. Of the resulting compounds, KU-2285 (a 2-nitroimidazole with an N1-substituent of CH2CF2CONHCH2-CH2OH) was considered the most useful as a hypoxic cell radiosensitizer. In this study, its in vivo radiosensitizing activity and acute toxicity were compared with those of etanidazole. The reduction potentials of KU-2285 and etanidazole were -0.96 V and -1.05 V vs Ag/Ag+ in N,N-dimethylformamide, respectively, and their respective octanol/water partition coefficients were 0.25 and 0.040. The in vivo radiosensitizing activity of KU-2285 was found to be similar to that of etanidazole at the same administration dose when assayed by an in vivo-in vitro assay, a growth delay assay, and a tumor control assay using SCC VII tumor or transplanted mammary tumor in C3H/He mice. Although the radiosensitizing activity of etanidazole was reduced when it was administered orally, there was no significant difference in the radiosensitizing activity of KU-2285 whether it was administered intravenously, intraperitoneally, or orally. The acute toxicity measured as the LD50/7 in 8-week-old female C3H/HeJ mice was found to be 2.4 g/kg (intravenously), 2.1 g/kg (intraperitonealy), and 4.25 g/kg (orally) for KU-2285, whereas it was 4.75 g/kg (intravenously) for etanidazole.
- OSTI ID:
- 5396204
- 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. 6; ISSN IOBPD; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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Cells
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560152 -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANOXIA
BODY
CHEMICAL PREPARATION
COMPARATIVE EVALUATIONS
DRUGS
EXPERIMENTAL NEOPLASMS
GLANDS
GROWTH
IN VITRO
IN VIVO
MAMMALS
MAMMARY GLANDS
MICE
ORGANS
RADIOSENSITIZERS
RODENTS
SYNTHESIS
TOXICITY
TUMOR CELLS
VERTEBRATES