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pH Dependence of 5-Fluorouracil Uptake Observed by in Vivo ³¹P and ¹⁹F Nuclear Magnetic Resonance Spectroscopy

Institut Curie-Biologie, INSERM U 219, Bât 112, Centre Universitaire, 91405 Orsay Cedex, France

Multinuclear nuclear magnetic resonance spectroscopy was used to follow the metabolism and kinetics of 5-fluorouracil (5FU) after i.v. administration at a dose of 100 mg/kg on Wistar rats. ³¹P spectra allow one to determine both the energetic status and the pH of the tissues under investigation, while serial ¹⁹F spectra reveal the drug clearance. Analyses of 5FU kinetics show that the half-life of 5FU elimination is about 35 min in tissue with a pH of 7.3. However, this half-life increases 2.5-fold when the local pH decreases below 6.9. Thus, acidification seems to induce a local retention of 5FU, which tends to prove the existence of active transport. This retention of the drug may have significant clinical implications for assessing and improving chemotherapy alone or in combination.

¹ To whom requests for reprints should be addressed.

Received 8/ 7/91. Accepted 9/ 5/91.

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