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

The metabolism of 5-fluorouracil (511) in tumors and livers of RII -1 tumor-bearing C3H mice given i.p. injections of 5FU was serially moni tored by "F magnetic resonance spectroscopy. The levels of 5FU and fluoronucleotide detected in the tumors after a dose of 130 mg/kg (n = 13) »ereless 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 a-fluoro-/S-ureidoprobionic acid and a-fluoro-/3-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 5FLI was 59 ±7 versus 28 ±2SEM min (P < 0.0001). There was a negative correlation between the levels of 5FL' catabolite (a-fluoro/J-ureidoprobionic acid and a-fluoro-/3-alanine) in liver and fluoronucleotide in tumor (r = 0.80; P = 0.0020), which indicates that the degradation in liver and the activation of 5FL in tumor are competing processes.