title: 18F-radiopharmacokinetics of [18F]-5-fluorouracil in a mouse bearing two colon tumors with a different 5-fluorouracil sensitivity: a study for a correlation with oncological results.
abstract: The tissue distribution and biodynamics of 18F-labelled 5-fluorouracil (FU) are described and studied for correlation with its in vivo antitumor activity. The in vivo model consisted of Balb/c mice bearing a FU sensitive (Colon 26-10 carcinoma) tumor in the left and a less responsive (Colon 26 carcinoma) tumor in the right abdominal side of the animal. Distribution and efflux of 18F-label from tumor, blood, and other tissues were determined by obduction at 0.5, 1, 2, 4, and 6 h postintravenous injection. For a comparison, the 18F-labeled 5-fluoro-6-hydroxy and cis-5-fluoro-6-ethoxy uracil adducts were studied in the same in vivo model. For 18F-FU it was found that the 18F-label tumor kinetics rapidly fell into a biphasic mode: a relatively short 18F beta phase (18F t1/2 beta 21 +/- 3 min), linked with the total body metabolic capacity and clearance of the animal, and a longer 18F gamma phase, linked with the intrinsic intratumoral FU metabolism (Colon 26-10: 18F t1/2 gamma 10.3 h; Colon 26: 18F t1/2 gamma 5.6 h). It is proposed that the observed faster 18F efflux of the less responsive Colon 26 corresponds to an enhanced breakdown of 5-fluoronucleotides to 5-fluoronucleosides and subsequent elimination from the tumor cells. It is concluded that on PET scanning, measurement of the dynamic 18F t1/2 gamma and 18F t1/2 beta parameter is of prime importance for an insight in the in vivo tumor biology of a patient.
authors.affiliation: Radio-Nuclide-Centre (RNC), Free University, Amsterdam, The Netherlands.
authors.forename: G W
authors.initials: GW
authors.lastname: Visser
authors.forename: C L
authors.initials: CL
authors.lastname: van der Wilt
authors.forename: R
authors.initials: R
authors.lastname: Wedzinga
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
authors.forename: J D
authors.initials: JD
authors.lastname: Herscheid
mesh_terms: D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D005468:Fluorodeoxyuridylate / Q000378:metabolism; D005472:Fluorouracil / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D013940:Thymidylate Synthase / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D005468:Fluorodeoxyuridylate; D013940:Thymidylate Synthase; D005472:Fluorouracil