The oxidation state of tissues influences their response to cancer therapy. We have devised a novel approach to the measurement of thiol redox which is based on the relative nuclear magnetic resonance signal intensity from carbon-13 adjacent to sulfur in metabolites of the redox-sensitive phosphorothioate drug, S-2-(3-methylaminopropylamino)ethylphosphorothioic acid (WR3689). Incubation of WR3689 metabolites under oxidizing conditions results in quantifiable changes in the 13C nuclear magnetic resonance spectrum stoichiometrically related to the degree of oxidation in mouse liver homogenate in vitro. Drug oxidation is competitive with the oxidation of tissue-derived thiol groups under these conditions. Noninvasive measurement of redox state may assist in designing more effective strategies for altering normal and malignant tissue response to cancer therapy.
These studies were supported by Program Project Grant 1-P01-CA42045 and Research Grant 1-R01-CA36485 from the National Cancer Institute, NIH, DHHS. This work has been presented in part at the 33rd Annual Meeting of the Society of Nuclear Medicine, Washington, DC, June 22–25, 1986, and at the Conference on Prediction of Tumor Treatment Response, Banff, Canada, April 21–24, 1987.