A new, potent 2-nitroimidazole nucleoside hypoxic cell radiosensitizer, RP170.
The radiosensitizing activity, acute toxicity and pharmacokinetics of RP170, a new hypoxic cell radiosensitizer, were compared with those of misonidazole (MISO) and SR2508. RP170 belongs to the group of 2-nitroimidazole nucleosides, which are designed to be selectively excluded from the neural tissue. The reduction potential of RP170 was similar to that of MISO and SR2508. The partition coefficients in octanol/water of RP170, MISO, and SR2508 were 0.094, 0.35, and 0.021, respectively. The radiosensitizing activity of RP170 was similar to that of MISO and SR2508 in vitro and in vivo. There was no significant difference in the radiosensitizing activity of RP170 in vivo between intravenous and intraperitoneal administration. The acute toxicity of RP170 was the same as that of SR2508. Pharmacokinetic evaluation showed that the concentration of RP170 in the brain was as low as that of SR2508. RP170 is expected to have the same radiosensitizing effects as MISO and SR2508, and to be less neurotoxic than MISO.
Sasai
K
K
Department of Radiology, Faculty of Medicine, Kyoto University.
Shibamoto
Y
Y
Takahashi
M
M
Abe
M
M
Wang
J
J
Zhou
L
L
Nishimoto
S
S
Kagiya
T
T
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D017341:Etanidazole; D005260:Female; D007928:Lethal Dose 50; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000494:pharmacology; D009593:Nitroimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D009705:Nucleosides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D009593:Nitroimidazoles; D009705:Nucleosides; D011838:Radiation-Sensitizing Agents; C060996:RP 170; D017341:Etanidazole; D008920:Misonidazole