F-19-(H-1) NUCLEAR OVERHAUSER EFFECT AND PROTON DECOUPLING OF 5-FLUOROURACIL AND ALPHA-FLUORO-BETA-ALANINE

F-19-{H-1} magnetic double-resonance experiments were performed on model solutions of the antitumor drug 5-fluorouracil (5-FU) and of alpha-fluoro-beta-alanine (FBAL) in order to improve F-19 NMR sensitivity for the application in pharmacokinetic studies in vivo. Upon driving the proton spins into saturation, a fluorine signal enhancement (nuclear Overhauser effect) was observed on the order of the theoretical NOE maximum gamma(H)/2 gamma, = 53% for purely dipolar coupled F-19-H-1 spin systems in extreme narrowing. The dependence of the effect on proton excitation frequency and temporal parameters was measured and cross-relaxation rate constants of 0.07 s(-1) (5-FU) and 0.19 s(-1) (FBAL) were determined. Irradiation of the proton spin system by a broad pulse during the F-19 signal detection period removed FBAL multiplet splittings completely and narrowed the linewidth of this resonance band by a factor of six, Application of proton presaturation in the F-19 NMR examination of a patient undergoing 5-FU chemotherapy enhanced the signal-to-noise ratio of the major 5-FU catabolite FBAL detected noninvasively in the liver. (C) 1995 Academic Press, Inc.