The effective use of
5-fluorouracil (5-FU) in
cancer therapy requires the noninvasive assessment of its transport, metabolism, and retention ("trapping") in the different tissues of the organism, particularly in the
tumor. We used a chemical-shift selective 19F magnetic resonance (MR) imaging technique to map selectively
5-FU and its major catabolite
alpha-fluoro-beta-alanine (
FBAL) in six ACI rats bearing
Morris hepatoma. After i.v. administration of 200 mg/kg-bw
5-FU, three metabolic MR maps were acquired consecutively in each animal: 1) an early 5-FU image (5-37 min post-injection (p.i.); dominant Fourier line, 8 min p.i.) characterizing the early uptake of 5-FU into the various tissues; 2) an
FBAL image (40-72 min p.i.; dominant Fourier line, 56 min p.i.) reflecting the catabolism of the
drug; and 3) a late 5-FU image (75-107 min p.i.; dominant Fourier line, 78 min p.i.) to assess the retention of unmetabolized 5-FU and its MR-visible anabolites. In the early 5-FU maps, the
drug was detected in all major organs (e.g., heart, liver, kidneys) as well as in the muscular system. The
FBAL maps showed no
FBAL accumulation in the
hepatoma which reveals that the
tumor cells have lost hepatocellular functions relevant for 5-FU catabolism. On the late 5-FU maps, a significant amount of 5-FU was detected in only one of the six Morris
hepatomas. The observation in this rat verifies directly that 5-FU can be trapped in solid
tumors. The images, moreover, emphasize the necessity of acquiring spatially-resolved MR data to detect metabolic
tumor heterogeneity.