This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by El-Tahtawy, A. Articles by Wolf, W. Search for Related Content PubMed PubMed Citation Articles by El-Tahtawy, A. Articles by Wolf, W.

In Vivo Measurements of Intratumoral Metabolism, Modulation, and Pharmacokinetics of 5-Fluorouracil, Using ¹⁹F Nuclear Magnetic Resonance Spectroscopy¹

Radiopharmacy Program, University of Southern California, Los Angeles, California 90033

In vivo ¹⁹F nuclear magnetic resonance spectroscopy was used to monitor and measure 5-fluorouracil and some of its cytotoxic anabolites directly in rats bearing the Walker 256 adenocarcinoma by using a 4.7-T horizontal bore magnet. A two-compartment subsystem model was used to estimate intratumoral transfer parameters. The apparent rate of formation of the nucleosides/tides in the tumor, K₂₁, changed following methotrexate pretreatment, from a value of 6.4 ± 2.4 to 15.5 ± 5.0. These values were statistically significant to P < 0.01. This 2-compartment model was validated by excising the tumors and measuring the ¹⁹F content of the acid soluble and the RNA fractions. The increase of the mean K₂₁ value (2.4) estimated in vivo correlated favorably with the increase of the levels of the fluorinated nucleosides/nucleotides (2.2) observed by in vitro analysis. The in vitro measurements also revealed that the increase in the fluorinated nucleosides was accompanied with a similar increase in 5-fluorouracil incorporation into the RNA fraction, which suggests that increases or decreases in the relative intensity of the fluorinated nucleoside/nucleotide signals observed in vivo could be indicative of similar changes of the nuclear magnetic resonance invisible fluorinated RNA.

The present study documents that it is now possible to estimate the pharmacokinetic behavior of 5-fluorouracil and of its active metabolites at its target site, tumor tissue, by using noninvasive measurements. Such measurements may provide useful means of assessing, during treatment, the possible effect of 5-fluorouracil on the tumor, and its response to treatment, both when used by itself as well as a function of biochemical modulation.

¹ This work was supported, in part, by Department of Energy Grant FG03-84ER60219, and by grants from the Margaret and Herbert Hoover Foundation. This work is part of the dissertation that was submitted by A. E. T. to the University of Southern California, as partial requirement for his Ph.D.

² To whom requests for reprints should be addressed, at Radiopharmacy Program, University of Southern California, 1985 Zonal Ave., Los Angeles, CA 90033.

Received 5/31/91. Accepted 8/27/91.

This article has been cited by other articles:

				J. R. Bading, P. B. Yoo, J. D. Fissekis, M. M. Alauddin, D. Z. D'Argenio, and P. S. Conti Kinetic Modeling of 5-Fluorouracil Anabolism in Colorectal Adenocarcinoma: A Positron Emission Tomography Study in Rats Cancer Res., July 1, 2003; 63(13): 3667 - 3674. [Abstract] [Full Text] [PDF]

				Y. Matsumura, K. Haruyama, T. Hamaguchi, K. Shirao, K. Muro, Y. Yamada, Y. Shimada, and K. Sugano Effect of a 3-hour Interval Between Methotrexate and 5-Fluorouracil in the Treatment of Metastatic Colorectal Cancer Jpn. J. Clin. Oncol., January 1, 2002; 32(1): 9 - 13. [Abstract] [Full Text] [PDF]

				B. A. Teicher, V. Chen, C. Shih, K. Menon, P. A. Forler, V. G. Phares, and T. Amsrud Treatment Regimens Including the Multitargeted Antifolate LY231514 in Human Tumor Xenografts Clin. Cancer Res., March 1, 2000; 6(3): 1016 - 1023. [Abstract] [Full Text]

				C. A. Presant, W. Wolf, V. Waluch, C. L. Wiseman, I. Weitz, and J. Shani Enhancement of Fluorouracil Uptake in Human Colorectal and Gastric Cancers by Interferon or by High-Dose Methotrexate: An In Vivo Human Study Using Noninvasive 19F-Magnetic Resonance Spectroscopy J. Clin. Oncol., January 14, 2000; 18(2): 255 - 255. [Abstract] [Full Text] [PDF]

				L. D. Stegman, A. Rehemtulla, B. Beattie, E. Kievit, T. S. Lawrence, R. G. Blasberg, J. G. Tjuvajev, and B. D. Ross Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy PNAS, August 17, 1999; 96(17): 9821 - 9826. [Abstract] [Full Text] [PDF]

				R. J.A. Harte, J. C. Matthews, S. M. O'Reilly, D.W. O. Tilsley, S. Osman, G. Brown, S. J. Luthra, F. Brady, T. Jones, and P. M. Price Tumor, Normal Tissue, and Plasma Pharmacokinetic Studies of Fluorouracil Biomodulation With N-Phosphonacetyl-L-aspartate, Folinic Acid, and Interferon Alfa J. Clin. Oncol., May 1, 1999; 17(5): 1580 - 1580. [Abstract] [Full Text] [PDF]