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¹⁹F Magnetic Resonance Spectroscopy Studies of the Metabolism of 5-Fluorouracil in Murine RIF-1 Tumors and Liver¹

Magnetic Resonance Research Center, Division of Radiology, Cleveland Clinic Foundation, Cleveland, Ohio 44915

The metabolism of 5-fluorouracil (5FU) in tumors and livers of RIF-1 tumor-bearing C3H mice given i.p. injections of 5FU was serially monitored by ¹⁹F magnetic resonance spectroscopy. The levels of 5FU and fluoronucleotide detected in the tumors after a dose of 130 mg/kg (n = 13) were less than one-third of those after 260-mg/kg 5FU (n = 14). During the days after these doses, tumor size decreased by 24 ± 3 and 52 ± 6 SEM%, respectively. A second 130-mg/kg dose, given at day 7 after the first 130-mg/kg dose, resulted in still lower tumor fluorine levels and little change in tumor size. There was a significant correlation between the magnetic resonance spectroscopy-detected fluoronucleotide levels and the shrinkage of tumors after the 260-mg/kg dose (r = 0.44; P = 0.024).

In mouse liver, the degradation of 5FU to -fluoro-ß-ureidoprobionic acid and -fluoro-ß-alanine after the 260-mg dose (n = 13) was slower than after a dose of 130 mg/kg (n = 14). For the respective doses, the half-life of 5FU was 59 ± 7 versus 28 ± 2 SEM min (P < 0.0001). There was a negative correlation between the levels of 5FU catabolite (-fluoro-ß-ureidoprobionic acid and -fluoro-ß-alanine) in liver and fluoronucleotide in tumor (r = - 0.80; P = 0.0020), which indicates that the degradation in liver and the activation of 5FU in tumor are competing processes.

¹ This work was supported by a grant from the NIH (CA 47227) and the Sherman Research Fund of the Cleveland Clinic Foundation.

² To whom requests for reprints should be addressed at MR Research Center, Desk L10, Cleveland Clinic Foundation, Cleveland, OH 44195.

Received 10/19/90. Accepted 12/20/90.