Intra- and extracellular fluorouracil uptake: assessment with contrast-enhanced metabolic F-19 MR imaging

To assess the extra- and intracellular uptake of the anticancer drug fluorouracil and its major catabolite alpha-fluoro-beta-alanine (FBAL) at gadolinium-enhanced fluorine-19 magnetic resonance (MR) imaging.

The relative fluorouracil and FBAL F-19 signal intensity increases due to extracellular and hepatobiliary paramagnetic contrast media were evaluated in ACI rats with transplanted Morris hepatoma. Control rats (n = 6) did not receive contrast medium; study rats received gadopentetate dimeglumine (n = 6) or gadoxetic acid (n = 6) before intravenous fluorouracil administration. The biodistributions of fluorouracil and FBAL were mapped at metabolic F-19 MR imaging at about 6 minutes (early distribution phase) and 64 minutes (metabolic phase), respectively, after drug administration.

Gadopentetate dimeglumine induced a significant (P < .05) increase in the signal 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 fluorouracil liver signal intensity did not increase with either contrast medium.

Whereas a marked amount of fluorouracil is in the extracellular tumor compartment 6 minutes after fluorouracil administration, the dominant fluorouracil signal intensity in the liver at 6 minutes arises from the intracellular compartment, which can be explained as retention of fluorouracil in hepatocytes. The marked increase in the FBAL signal intensity about 1 hour after fluorouracil administration is congruent with our observation of a high intracellular uptake of gadoxetic acid in the liver at about 1 hour.