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Li CW , Negendank WG , PadavicShaller KA , Odwyer PJ , MurphyBoesch J , Brown TR
Quantitation of 5-fluorouracil catabolism in human liver in vivo by three-dimensional localized F-19 magnetic resonance spectroscopy
Clinical Cancer Research. 1996 Feb;2(2) :339-345
PMID: ISI:A1996TU87500013   
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Abstract
The development of clinical applications of F-19 magnetic resonance (MR) spectroscopy of 5-fluorouracil (5-FU) has been limited by the inability to localize F-19 spectra to specific regions of interest, making it difficult to quantitate drug and metabolite concentrations accurately, To develop methodology for quantitation, we studied the liver of patients receiving rapid bolus i.v. injections of 5-FU. In serial studies, 5-FU disappeared from the liver within 17-26 min, and its catabolite, alpha-fluoro-beta-alanine (FBAL), rose to reach a plateau after 40 min. A high peak level of fluoro-ureido- propionic acid preceded that of FBAL in only one patient, and dihydrofluorouracil was never observed, During the plateau, we obtained MR imaging-directed F-19 MR spectra localized using three-dimensional chemical shift imaging, The spin-lattice relaxation time of FBAL in liver, measured using a variable nutation angle method, was 1.6 +/- 0.2 s (mean +/- SD; n = 5). The concentration of FBAL at 60 +/- 10 min after injection was 1.0 +/- 0.2 mM in liver (mean +/- SD; n = 7). This amount represents similar to 20% of the injected dose and 1.4 times the initial hepatic 5-FU concentration, Our approach may permit one to obtain molar concentrations of fluoropyrimidine metabolites simultaneously in hepatic cancers and surrounding liver, and it helps expand pharmacokinetic modeling of fluoropyrimidine catabolism.
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Times Cited: 8 English Article TU875 CLIN CANCER RES