A fluorinated 2-nitroimidazole, KU-2285, as a new hypoxic cell radiosensitizer.
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.[1]References
- A fluorinated 2-nitroimidazole, KU-2285, as a new hypoxic cell radiosensitizer. Sasai, K., Nishimoto, S., Shimokawa, K., Hisanaga, Y., Kitakabu, Y., Shibamoto, Y., Zhou, L., Wang, J., Takahashi, M., Kagiya, T. Int. J. Radiat. Oncol. Biol. Phys. (1991) [Pubmed]
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