INTRACELLULAR AND EXTRACELLULAR FLUOROURACIL UPTAKE - ASSESSMENT WITHCONTRAST-ENHANCED METABOLIC F-19 MR-IMAGING

PURPOSE: To assess the extra- and intracellular uptake of the anticanc er drug fluorouracil and its major catabolite alpha-fluoro-beta-alanin e (FBAL) at gadolinium-enhanced fluorine-19 magnetic resonance (MR) im aging. MATERIALS AND METHODS: The relative fluorouracil and FBAL F-19 signal intensity increases due to extracellular and hepatobiliary para magnetic contrast media were evaluated in ACI rats with transplanted M orris hepatoma. Control rats (n = 6) did not receive contrast medium; study rats received gadopentetate dimeglumine (n = 6) or gadoxetic aci d (n = 6) before intravenous fluorouracil administration. The biodistr ibutions of fluorouracil and FBAL were mapped at metabolic F-19 MR ima ging at about 6 minutes (early distribution phase) and 64 minutes (met abolic phase), respectively, after drug administration. RESULTS: Gadop entetate dimeglumine induced a significant (P < .05) increase in the s ignal intensity of fluorouracil (70%) in the hepatoma; gadoxetic acid induced a significant increase in the signal intensity of fluorouracil in the hepatoma (85%) and of FBAL in the liver (71%). The fluorouraci l liver signal intensity did not increase with either contrast medium. CONCLUSION: Whereas a marked amount of fluorouracil is in the extrace llular tumor compartment 6 minutes after fluorouracil administration, the dominant fluorouracil signal intensity in the liver at 6 minutes a rises from the intracellular compartment, which can be explained as re tention of fluorouracil in hepatocytes. The marked increase in the FBA L signal intensity about 1 hour after fluorouracil administration is c ongruent with our observation of a high intracellular uptake of gadoxe tic acid in the liver at about 1 hour.