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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Forschungsschwerpunkt Radiologische Diagnostik und Therapie (Research Program Radiologic Diagnostics and Therapy), Deutsches Krebsforschungszentrum, Heidelberg, Germany.
G
G
Brix
M E
ME
Bellemann
L
L
Gerlach
U
U
Haberkorn
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D003287:Contrast Media; D005461:Fluorine; D005472:Fluorouracil / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods; D008297:Male; D009368:Neoplasm Transplantation; D019047:Phantoms, Imaging; D051381:Rats; D011912:Rats, Inbred ACI; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D003287:Contrast Media; C073590:gadolinium ethoxybenzyl DTPA; D005461:Fluorine; D019786:Gadolinium DTPA; D005472:Fluorouracil