The radiosensitizing efficiencies of 4 structural analogues of misonidazole (MISO) have been compared with that of the parent compound. Three of these were charged basic compounds, previously shown in vitro to be 10 times more efficient. Enhancement ratios were measured from pairs of tumour growth-delay curves for the mouse fibrosarcoma SA Fab. Two routes of administration and ranges of drug dose and intervals between injection and irradiation were tested. Drug concentrations in blood, brain and tumour were measured using highperformance liquid chromatography. The peak concentration in tumours coincided with the peak in radiosensitization: 20 min after i.v. injection and 40 min after i.p. injection. The concentration in tumours was similar for either route. Comparison of radiosensitizing efficiency on the basis of equal administered dose showed no difference between the 5 compounds, but after equimolar doses the charged compounds achieved lower tumour concentrations. Comparison of sensitizing efficiency on the basis of tumour concentration showed that they were 3 times more potent than MISO, as predicted from their higher electron-affinity. The resultant improvement in radiosensitization at low, clinically relevant, concentrations is so slight that any therapeutic benefit would depend on reduced drug toxicity in man.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.