This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Presant, C. A. Articles by Shani, J. Search for Related Content PubMed PubMed Citation Articles by Presant, C. A. Articles by Shani, J. Social Bookmarking                            What's this?

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

From the Los Angeles Oncologic Institute at the St. Vincent Medical Center; University of Southern California School of Pharmacy; and California Cancer Medical Center, Los Angeles, CA; and the David R. Bloom Center for Pharmacy at the Hebrew University of Jerusalem, Jerusalem, Israel.

Address reprint requests to Walter Wolf, PhD, Pharmacokinetic Imaging Program, University of Southern California, 1985 Zonal Ave, Los Angeles, CA 90033; email wwolfw{at}hsc.usc.edu

PURPOSE: To study whether two modulators, high-dose methotrexate (MTX) and interferon alfa-2a (IFN-2a) will alter the intratumoral pharmacokinetics of fluorouracil (5-FU).

PATIENTS AND METHODS: Five patients, two with gastric cancer and three with colorectal cancer, who had metastatic tumor nodules in their livers were studied dynamically in vivo after 5-FU injection. In a magnetic resonance imaging unit, noninvasive ¹⁹F-magnetic resonance spectroscopy (MRS) was used to detect ¹⁹F signals from 5-FU and its metabolites.

RESULTS: The intratumoral half-life (t_1/2) of 5-FU in these tumors ranged from 18.8 minutes to 42.3 minutes. Four of the five patients exhibited increases in the t_1/2 of 5-FU after intravenous (IV) administration of MTX or IFN-2a. In the two patients with gastric cancer who received IV high-dose MTX followed by IV 5-FU, increases were seen in either the total t_1/2 of 5-FU (41.8%) or in the t_1/2 of the phase (150%). In the three patients with colorectal cancer who received IV IFN-2a followed by IV 5-FU, the two patients with partial responses had increases in the t_1/2 of 5-FU of 41% and 30.2%, whereas the nonresponder had a nonsignificant increase (5.6%) in the t_1/2 of 5-FU.

CONCLUSIONS: These results document that the in vivo modulation of the tumoral pharmacokinetics of 5-FU can be measured noninvasively by ¹⁹F-MRS and suggest that such information correlates with subsequent clinical outcomes. The findings also indicate that IFN-2a and high-dose MTX can increase the intratumoral 5-FU in some patients. Such information, obtained prospectively in vivo, may assist in better individual cancer patient management and in developing novel drug combinations.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				N. Panayotatos Drug-binding Cavities in Long-Lived Biologics: Cause for Concern but Also Potential Benefit J. Clin. Pharmacol., October 1, 2008; 48(10): 1208 - 1211. [Abstract] [Full Text] [PDF]

				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]

				J. Pehoushek and K. J. Smith Imiquimod and 5% Fluorouracil Therapy for Anal and Perianal Squamous Cell Carcinoma In Situ in an HIV-1-Positive Man Arch Dermatol, January 1, 2001; 137(1): 14 - 16. [Full Text] [PDF]