In vivo monitoring of changes in 5‐fluorouracil metabolism induced by methotrexate measured by 19F NMR spectroscopy

Jason A. Koutcher, Robert C. Sawyer, Alice B. Kornblith, Robert L. Stolfi, Daniel S. Martin, Mary L. Devitt, David Cowburn, Charles W. Young

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Abstract

We have used in vivo 19F NMR spectroscopy to study the metabolism of 5‐fluorouracil (FUra) in tumors with and without pretreatment with methotrexate (MTX). Using the CD8F1 murine mammary tumor as an in vivo model, we observed signals from FUra, α‐fluoro‐β‐alanine (FβALA), α‐fluoro‐β‐ureidopropionic acid (FUPA), and 5‐fluorouracil‐nucleotides (FUN) after intravenous or intraperitoneal injection of 150 mg/kg FUra. Formation of FUN was increased about 1.7‐fold in CD8F1 tumor with methotrexate pretreatment as determined by acid extraction and HPLC analysis. A comparison of in vivo NMR spectra from FUra and sequential MTX + FUra‐treated tumors showed a significantly higher ratio of the FUN signal to the initial total 19F signal in the MTX + FUra‐treated tumors (p < 0.001) for animals receiving FUra either intravenously or intraperi‐toneally. In addition, tumors treated with MTX + FUra had significantly longer time durations during which FUN was detected, independent of the mode of administration. These experiments indicate that in vivo 19F NMR spectroscopy can be used to noninvasively monitor alterations of 5‐fluorouracil metabolism that occur with administration of modulating agents such as methotrexate. Further studies, in both murine tumor models and patients, are indicated to determine if these results can be correlated with tumor response. © 1991 Academic Press, Inc.

Original languageEnglish (US)
Pages (from-to)113-123
Number of pages11
JournalMagnetic Resonance in Medicine
Volume19
Issue number1
DOIs
Publication statusPublished - May 1991
Externally publishedYes

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ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Koutcher, J. A., Sawyer, R. C., Kornblith, A. B., Stolfi, R. L., Martin, D. S., Devitt, M. L., ... Young, C. W. (1991). In vivo monitoring of changes in 5‐fluorouracil metabolism induced by methotrexate measured by 19F NMR spectroscopy. Magnetic Resonance in Medicine, 19(1), 113-123. https://doi.org/10.1002/mrm.1910190111