title: In vivo monitoring of capecitabine metabolism in human liver by 19fluorine magnetic resonance spectroscopy at 1.5 and 3 Tesla field strength.
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.
authors: Departments of Medical Oncology and Radiology, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands. h.vanlaarhoven@onco.umcn.nl
authors: Hanneke W M
authors: HW
authors: van Laarhoven
authors: Dennis W J
authors: DW
authors: Klomp
authors: Yvonne J L
authors: YJ
authors: Kamm
authors: Cornelis J A
authors: CJ
authors: Punt
authors: Arend
authors: A
authors: Heerschap
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005467:Floxuridine / Q000378:metabolism / Q000493:pharmacokinetics; D005461:Fluorine; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D005467:Floxuridine; D003841:Deoxycytidine; D005461:Fluorine; D000069287:Capecitabine; C418208:5'-deoxy-5-fluorocytidine; D005472:Fluorouracil; C025034:doxifluridine