Abstract
High-resolution 19F nuclear magnetic resonance spectroscopy at 7 T was used to study the effect of modulators on the metabolism of 5-fluorouracil (5-FUra, 115 mg/kg i.p.) in C38 murine colon tumors grown in C57BL/6 mice. Distinct 5-FUra metabolite patterns were found in perchloric acid extracts of these tumors after treatment.
The 19F nuclear magnetic resonance spectra exhibited resonances representing 5-FUra, the catabolites α-fluoro-β-ureidopropionic acid and α-fluoro-β-alanine, as well as four distinct fluoronucleotide anabolites. Using this model system the effect of several modulators on 5-FUra tumor metabolite patterns was investigated: methotrexate (300 mg/kg); α-interferon (105 IU/animal); N-(phosphonacetyl)-l-aspartate (100 and 250 mg/kg); and leucovorin (300 and 750 mg/kg). A significant increase in the anabolite:catabolite ratio was observed for the groups treated with 5-FUra in combination with the modulators methotrexate (n = 8), α-interferon (n = 7), and high-dose leucovorin (n = 14), but not for low-dose leucovorin (n = 7). Cotreatment with high-dose N-(phosphonacetyl)-l-aspartate (n = 8) resulted in a significant decrease in the anabolite: catabolite ratio compared to treatment with 5-FUra alone (n = 16). Possible correlations of metabolite profiles with therapy response are discussed.
Footnotes
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↵1 This work was supported by the Dutch Cancer Society.
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↵2 To whom requests for reprints should be addressed.
- Received September 27, 1993.
- Accepted June 8, 1994.
- ©1994 American Association for Cancer Research.
Volume 54, Issue 16
