Direct detection of intratumoral 5-fluorouracil trapping using metabolic F-19 MR imaging

The effective use of 5-fluorouracil (5-FU) in cancer therapy requires the n oninvasive assessment of its transport, metabolism, and retention ("trappin g") in the different tissues of the organism, particularly in the tumor. We used a chemical-shift selective F-19 magnetic resonance (MR) imaging techn ique to map selectively 5-FU and its major catabolite alpha-fluoro-beta-ala nine (FBAL) in six ACI rats bearing Morris hepatoma. After i.v. administrat ion of 200 mg/kg-bw 5-FU, three metabolic MR maps were acquired consecutive ly 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 Fourie r 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 t he retention of unmetabolized 5-FU and its MR-visible anabolites. In the ea rly 5-FU maps, the drug was detected in all major organs (e.g., heart, live r, 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 map s, 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 t rapped in solid tumors. The images, moreover, emphasize the necessity of ac quiring spatially-resolved MR data to detect metabolic tumor heterogeneity. (C) 1998 Elsevier Science Inc.