Tissue distribution of [18F]-5-fluorouracil in mice: effects of route of administration, strain, tumour and dose.
In a study investigating the usefulness of 5-fluorouracil labelled with fluorine 18 [( 18F]-5-FU) in cancer chemotherapy, the tissue distribution of the radiolabel was determined in mice at 2, 4 and 6 h after administration by varying several parameters such as the mode of administration, the strain of mouse, the presence of a tumour and the total dose of 5-FU. The tissue distribution of fluorine 18 after i.p. injection pointed to an altered behaviour of the drug and/or its metabolites when compared with values obtained after i.v. injection, but no difference was found in the accumulation of radiolabel in the tumour. A comparison of non-tumour-bearing BALB/c and C57Bl/6 mice revealed that the latter showed a higher radiolabel accumulation of the drug and its metabolites in the liver, kidney, intestines and coecum (P less than 0.05 at 2 and 4 h). In tumour-bearing mice, especially at 2 h, the tissue accumulation of radiolabel was found to be significantly higher than in non-tumour-bearing controls (in BALB/c mice bearing colon 26 carcinoma, P less than 0.05 for all tissues; in C57Bl/6 mice bearing colon 38 carcinoma, P less than 0.05 for the blood, lung, liver, kidney, large intestines, coecum and muscle). Finally, a comparison of injections of a tracer dose of [18F]-5-FU (2.5 mg/kg) vs a therapeutic dose (100 mg/kg) revealed only small differences in the accumulation of fluorine 18 in the liver and kidney.
Visser
G W
GW
Radio-Nuclide-Centre (RNC), Free University, Amsterdam, The Netherlands.
Gorree
G C
GC
Peters
G J
GJ
Herscheid
J D
JD
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005462:Fluorine Radioisotopes; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013997:Time Factors; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D005472:Fluorouracil