In vivo 19F nuclear magnetic resonance spectroscopy: a potential monitor of 5-fluorouracil pharmacokinetics and metabolism

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Abstract
In vivo 19F nuclear magnetic resonance (NMR) spectroscopy has the potential to non-invasively measure the concentration of 5-fluorouracil (FUra) and some of its metabolites in humans. Such a measure could be useful in predicting and optimizing the response of individual patients treated with FUra. The ability of 19F NMR to monitor FUra metabolism in situ in rodent tumors and liver and in human liver has been demonstrated. However, the potential impact of this technique as a predictor of FUra response in individual patients is limited by both the sensitivity (i.e., limit of detection) and the resolution (i.e., ability to distinguish among magnetically similar metabolites) of NMR. To date, the ability of in vivo 19F NMR spectroscopy to provide information that can distinguish FUra-sensitive from FUra-insensitive tumors has not been established. This crucial point should be addressed in the immediate future in studies using the best of experimental conditions (i.e., optimum sensitivity and resolution in well-defined rodent tumor models with NMR methodology appropriate for measurement of absolute metabolite concentrations). The information gained from such studies and any new technical developments to enhance in vivo NMR sensitivity should be directly applicable to any future application of 19F NMR spectroscopy in clinical FUra therapy.