Using chemical shift-selective (19)F magnetic resonance (MR) imaging, we investigated the biomodulating action of
5-bromovinyluracil (BVU) on the degradation of the anticancer
drug 5-fluorouracil (5-FU) to its major catabolite
alpha-fluoro-beta-alanine (
FBAL) and the tissue uptake of
5-FU in ACI rats with transplanted
Morris hepatoma. Rats in the control group (n = 7) received 200 mg/kg
body weight of
5-FU intravenously, whereas the rats in the BVU group (n = 7) additionally received 30 mg/kg
body weight of BVU intraperitoneally about 45 min before
5-FU injection. In each animal examination, three selective (19)F MR images were acquired sequentially after
5-FU administration with an acquisition time of 32 min each: an early
5-FU image (dominant Fourier line, 8 min p.i.) that characterized the early uptake of the
drug into the various tissues, an
FBAL image (dominant Fourier line, 56 min p.i.) that reflected the catabolism of the
drug, and a late
5-FU image (dominant Fourier line, 78 min p.i.) that assessed the retention ("trapping") of unmetabolized
5-FU and its MR-visible anabolites. Pretreatment with BVU resulted in a highly statistical significant decrease (P < 0.001) of the
FBAL signal in the liver. The marked effect of BVU on
5-FU degradation, however, improved neither the early uptake nor the retention of
5-FU in skeletal muscle and
tumor tissue (P > 0.7). Moreover, our results indicate that
5-FU tumor uptake is not only dependent on the plasma concentration of unmetabolized
5-FU but is also determined by
tumor-specific factors, these showing considerable variations between individual
neoplasms. Magn Reson Med 42:936-943, 1999.