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

• Published in: Nuclear medicine and biology 1996-04, Vol.23 (3), p.333-342
• Main Authors: Visser, Gerard W.M., van der Wilt, Clasina L., Wedzinga, Rinny, Peters, Godefridus J., Herscheid, Jacobus D.M.
• Format: Article
• Language: English
• Subjects: 18F-Radiopharmacokinetics; 5-Fluorouracil sensitivity; [ 18F]-5-Fluorouracil; Animals; Biological and medical sciences; Cell Line; Colon carcinoma; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Contrast media. Radiopharmaceuticals; Female; Fluorine Radioisotopes - pharmacokinetics; Fluorodeoxyuridylate - metabolism; Fluorouracil - blood; Fluorouracil - pharmacokinetics; Fluorouracil - therapeutic use; Isotope Labeling - methods; Kinetics; Medical sciences; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; Thymidylate Synthase - metabolism; Tissue Distribution
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/0969-8051(95)02088-8

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 t 1 2 β 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 t 1 2 γ 10.3 h; Colon 26: 18F t 1 2 γ 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 t 1 2 and 18F t 1 2 β parameter is of prime importance for an insight in the in vivo tumor biology of a patient.