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

Abstract

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.