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Chemotherapy in non-responding cancer patients leads to unnecessary toxicity. A marker is therefore required that can predict the sensitivity of a specific tumour to chemotherapy, which would enable individualisation of therapy. 19F MR spectroscopy (19F MRS) can be used to monitor the metabolism of fluorinated drugs. The aim of this study was to develop a method for quantified localised detection of fluorinated compounds in human liver. For this purpose, sensitivity-optimised localised 19F MRS methods at 3 T were used to detect MR signals from capecitabine, 5′DFUR, 5′DFCR and FBAL after oral intake of capecitabine. As the radio-frequency (rf) coil is made tuneable to 19F and 1H, the same localisation method is applied to obtain 1H MR signals of water and of the 19F metabolites. In addition, T1 measurements have been performed to correct for measurement-induced saturation effects. Finally, absolute tissue concentrations of capecitabine metabolites were obtained in vivo, which revealed a substantial spatial heterogeneity of these metabolites in human liver after chemotherapy. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: 19Fluorine magnetic resonance spectroscopy (19F MRS) offers unique possibilities for monitoring the pharmacokinetics of fluoropyrimidines in vivo in tumors and normal tissue in a non-invasive way, both in animals and in patients. This method may therefore be useful for predicting response to fluoropyrimidine-based therapy with or without the effects of modulating agents, and this may be of value for the individualization of anticancer therapy and the strategic development of new anticancer drugs. 19F MRS has been very valuable in elucidating the basic aspects of fluoropyrimidine metabolism, especially in animal studies. Studies in humans have indicated its clinical potential, but widespread application has been hampered by the relatively low detection sensitivity of the method. The recent introduction of clinical MR scanners with magnetic fields above 1.5T may stimulate increased clinical use of 19F MRS. [Copyright &y& Elsevier]

Chemotherapy in non-responding cancer patients leads to unnecessary toxicity. A marker is therefore required that can predict the sensitivity of a specific tumour to chemotherapy, which would enable individualisation of therapy. 19F MR spectroscopy (19F MRS) can be used to monitor the metabolism of fluorinated drugs. The aim of this study was to develop a method for quantified localised detection of fluorinated compounds in human liver. For this purpose, sensitivity-optimised localised 19F MRS methods at 3 T were used to detect MR signals from capecitabine, 5'DFUR, 5'DFCR and FBAL after oral intake of capecitabine. As the radio-frequency (rf) coil is made tuneable to 19F and 1H, the same localisation method is applied to obtain 1H MR signals of water and of the 19F metabolites. In addition, T1 measurements have been performed to correct for measurement-induced saturation effects. Finally, absolute tissue concentrations of capecitabine metabolites were obtained in vivo, which revealed a substantial spatial heterogeneity of these metabolites in human liver after chemotherapy., (Copyright 2006 John Wiley & Sons, Ltd.)

In metastatic colorectal cancer the oral 5-fluorouracil (5FU) prodrug capecitabine is used with increasing frequency as an alternative to i.v. 5FU administration. The rate of conversion of capecitabine into 5'deoxy-5-fluorouridine has been related to tumor response, and 5FU catabolites have been associated with 5FU-related systemic toxicity. Here we demonstrate for the first time that capecitabine, its metabolites 5'deoxy-5-fluorocytidine and 5'deoxy-5-fluorouridine, and its catabolites 5-fluoro-ureido-propionic acid, alpha-fluoro-beta-alanine, and alpha-fluoro-beta-alanine-bile acid conjugate can be monitored in vivo by (19)fluorine magnetic resonance spectroscopy ((19)F MRS) in the liver of patients with metastatic colorectal cancer. Moreover, we demonstrate an improved signal-to-noise ratio and spectral resolution of the (19)F MRS spectra when measurements are performed at 3 T field strength as compared with measurements at the common clinical field strength of 1.5 T. We conclude that assessment of capecitabine metabolism in patients by (19)F MRS is a promising noninvasive tool for the prediction of its efficacy and toxicity, especially at the now currently available clinical field strength of 3 T.