title: Radiosensitization by 2-nitroimidazole nucleoside analog RP-170: radiosensitizing effects under both intravenous and oral administration.
abstract: The radiosensitizing activity, pharmacokinetics and toxicity of RP-170, 2-nitroimidazole nucleoside analog, were investigated and compared with those of etanidazole (SR-2508). An intravenous administration (i.v.) of 100 mg/kg of RP-170 or the same dose of etanidazole showed an equal sensitizer enhancement ratio (SER) of about 1.4 to solid EMT6 tumor under in vivo-in vitro assay and a virtually equal SER of 1.4-1.5 to solid SCC VII tumor under tumor growth delay assay. As predicted from the low partition coefficient, lower drug levels in neural tissue and more rapid serum elimination of RP-170 and etanidazole produced lower acute toxicity than lipophilic sensitizers (e.g., misonidazole). The major advantage of RP-170 over etanidazole is that it has a second route of administration. In contrast to etanidazole, in which the administration route is limited to intravenous injection, with RP-170 oral administration also exhibited effective distribution to tumors, sensitizing radiation activity to solid EMT6 and SCC VII tumors. Moreover, LD50 in mice of RP-170 (4.3 g/kg on i.v.) was increased to 5.2 g/kg by oral administration. This availability of two routes of administration indicates RP-170 as a promising hypoxic cell radiosensitizer for clinical use.
authors.affiliation: Department of Radiation Oncology, School of Medicine, Tokai University, Isehara, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Murayama
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: C
authors.initials: C
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Miyata
authors.forename: T
authors.initials: T
authors.lastname: Shoji
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: T
authors.initials: T
authors.lastname: Mori
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003131:Combined Modality Therapy; D017341:Etanidazole; D005260:Female; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000532:radiotherapy*; D009593:Nitroimidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D009705:Nucleosides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009593:Nitroimidazoles; D009705:Nucleosides; D011838:Radiation-Sensitizing Agents; C060996:RP 170; D017341:Etanidazole