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  • Title: Enhancement of fluorouracil uptake in human colorectal and gastric cancers by interferon or by high-dose methotrexate: An in vivo human study using noninvasive (19)F-magnetic resonance spectroscopy.
    Author: Presant CA, Wolf W, Waluch V, Wiseman CL, Weitz I, Shani J.
    Journal: J Clin Oncol; 2000 Jan; 18(2):255-61. PubMed ID: 10637237.
    Abstract:
    PURPOSE: To study whether two modulators, high-dose methotrexate (MTX) and interferon alfa-2a (IFNalpha-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 (19)F-magnetic resonance spectroscopy (MRS) was used to detect (19)F 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 IFNalpha-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 alpha phase (150%). In the three patients with colorectal cancer who received IV IFNalpha-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 (19)F-MRS and suggest that such information correlates with subsequent clinical outcomes. The findings also indicate that IFNalpha-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.
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