19F magnetic resonance spectroscopy studies of the metabolism of 5-fluorouracil in murine RIF-1 tumors and liver.
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 alpha-fluoro-beta-ureidoprobionic acid and alpha-fluoro-beta-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 less than 0.0001). There was a negative correlation between the levels of 5FU catabolite (alpha-fluoro-beta-ureidoprobionic acid and alpha-fluoro-beta-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.
Sijens
P E
PE
Magnetic Resonance Research Center, Cleveland Clinic Foundation, Ohio 44195.
Huang
Y M
YM
Baldwin
N J
NJ
Ng
T C
TC
D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism*; D005472:Fluorouracil / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D012044:Regression Analysis
D005472:Fluorouracil