Radiosensitization by a new nucleoside analogue: 1-(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl-2-nitroimidazole (RP-170)

Journal Article · Fri Sep 01 00:00:00 EDT 1989 · International Journal of Radiation Oncology, Biology and Physics; (USA)

DOI:https://doi.org/10.1016/0360-3016(89)90109-0· OSTI ID:5478844

Murayama, C; Suzuki, A; Suzuki, T; Miyata, Y; Sakaguchi, M; Tanabe, Y; Tanaka, N; Mori, T ^[1]

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1. Tokai Univ. (Japan)

A new potent hypoxic cell sensitizer, a 2-nitroimidazole nucleoside analogue having methoxyglycerol as a sugar moiety at the N-1 position of the imidazole ring (RP-170), has been synthesized. Its radiosensitizing activities in vitro and in vivo were investigated and compared with those of misonidazole (MISO) and etanidazole (SR-2508). As might be expected from the almost identical electron affinities of the three compounds, they were equally effective against hypoxic EMT6 cells in vitro. The in vivo-in vitro excision analysis showed that RP-170 was also as effective as MISO and etanidazole to radiosensitize solid tumor cells in vivo. An intraperitoneal administration of 200 mg/kg of RP-170 and an intravenous administration of the same dose of etanidazole showed an equal sensitizer-enhancement ratio of 1.51 to solid EMT6/KU tumors. Its effectiveness was also demonstrated by growth delay assay using solid SCCVII tumors. As predicted from the low partition coefficient, RP-170 and etanidazole showed apparently lower toxicity in vivo than MISO; their LD50/14 were 4.3, 4.8, and 1.8 g/kg in our experiment, respectively. Moreover, RP-170 showed fast clearance from serum in mice (t1/2 = 10.24 min) and poor penetration into neural tissues. Although RP-170 does not show any advantages over etanidazole in terms of sensitization or toxicity, RP-170 might be preferable under certain circumstances because it can be given orally.

• OSTI ID: 5478844
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (USA), Vol. 17:3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
RADIOSENSITIZERS
CHEMICAL PREPARATION
ANOXIA
COMPARATIVE EVALUATIONS
IN VITRO
MICE
MISONIDAZOLE
NUCLEOSIDES
TUMOR CELLS
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
DRUGS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MAMMALS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RIBOSIDES
RODENTS
SYNTHESIS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture
560152 - Radiation Effects on Animals- Animals