In vivo testing of a 2-nitroimidazole radiosensitizer (Ro 03-8799) using repeated administration

Journal Article · Mon Mar 01 04:00:00 EST 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90665-4· OSTI ID:6704238

Williams, M V; Chir, B; Denekamp, J; Minchinton, A I; Stratford, M R.L.

The radiosensitizing efficiency of a novel 2-nitroimidazole (Ro 03-8799) has been compared with that of misonidazole. Each compound was assessed by constructing dose response curves for regrowth delay using a range of drug doses. The concentration of each compound was measured in tumor homogenates with high performance liquid chromatography (HPLC). When compared on the basis of administered dose the new compound was no more efficient than misonidazole. Comparison on the basis of measured tumor concentrations showed that Ro 03-8799 was 3-4 times more efficient than misonidazole, but only at very high drug levels. Previous in vitro studies had shown a constant 10-fold difference in potency. In order to eliminate possible artifacts caused by the short half life in mice, repeated injections of Ro 03-8799 were used to maintain a constant tumor concentration for two hours before irradiation. No increase in effectiveness was observed with prolonged exposure. This is a charged compound whose distribution is pH dependent; gross tumor levels should therefore be interpreted with caution.

• Research Organization: Mount Vernon Hospital, Northwood, England
• OSTI ID: 6704238
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8:3/4; ISSN IOBPD
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
CHROMATOGRAPHY
CHRONIC EXPOSURE
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
GROWTH
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IN VIVO
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MICE
MISONIDAZOLE
NEOPLASMS
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHARMACOLOGY
RADIOSENSITIZERS
RODENTS
SEPARATION PROCESSES
VERTEBRATES