Amide-, amine-, and hydroxyl-water proton exchange can generate MRI contrast through chemical exchange saturation transfer (CEST). In this study, we show that thiol-water proton exchange can also generate quantifiable CEST effects under near-physiological conditions (pH = 7.2 and 37°C) through the characterization of the pH dependence of thiol proton exchange in phosphate-buffered solutions of glutathione, cysteine, and N-acetylcysteine. The spontaneous, base-catalyzed, and buffer-catalyzed exchange contributions to the thiol exchange were analyzed. The thiol-water proton exchange of glutathione and cysteine was found to be too fast to generate a CEST effect around neutral pH due to significant base catalysis. The thiol-water proton exchange of N-acetylcysteine was found to be much slower, yet still in the fast-exchange regime with significant base and buffer catalysis, resulting in a 9.5% attenuation of the water signal at pH 7.2 in a slice-selective CEST NMR experiment. Furthermore, the N-acetylcysteine thiol CEST was also detectable in human serum albumin and agarose phantoms.
Keywords: N-acetylcysteine; chemical exchange saturation transfer (CEST); cysteine; exchange rate quantification; glutathione; pH; thiol CEST; thiol proton exchange.
© 2019 John Wiley & Sons, Ltd.