In vivo monitoring of capecitabine metabolism in human liver by 19fluorine magnetic resonance spectroscopy at 1.5 and 3 Tesla field strength

Cancer Res. 2003 Nov 15;63(22):7609-12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / metabolism
  • Antimetabolites, Antineoplastic / pharmacokinetics*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Capecitabine
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / metabolism
  • Deoxycytidine / pharmacokinetics*
  • Deoxycytidine / therapeutic use
  • Female
  • Floxuridine / metabolism
  • Floxuridine / pharmacokinetics
  • Fluorine
  • Fluorouracil / analogs & derivatives
  • Humans
  • Liver / metabolism
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / secondary*
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Prodrugs / pharmacokinetics
  • Prodrugs / therapeutic use

Substances

  • Antimetabolites, Antineoplastic
  • Prodrugs
  • Floxuridine
  • Deoxycytidine
  • Fluorine
  • Capecitabine
  • 5'-deoxy-5-fluorocytidine
  • Fluorouracil
  • doxifluridine