F-18 RADIOPHARMACOKINETICS OF [F-18] 5-FLUOROURACIL IN A MOUSE BEARING 2 COLON TUMORS WITH A DIFFERENT 5-FLUOROURACIL SENSITIVITY - A STUDYFOR A CORRELATION WITH ONCOLOGICAL RESULTS

The tissue distribution and biodynamics of F-18-labelled 5-fluorouraci l (FU) are described and studied for correlation with its in vivo anti tumor activity. The in vivo model consisted of Balb/c mice bearing a F U sensitive (Colon 26-10 carcinoma) tumor in the left and a less respo nsive (Colon 26 carcinoma) tumor in the right abdominal side of the an imal. Distribution and efflux of F-18-label from tumor, blood, and oth er tissues were determined by obduction at 0.5, 1, 2, 4, and 6 h posti ntravenous injection. For a comparison, the F-18-labeled 5-fluoro-6-hy droxy and cis-5-fluoro-6-ethoxy uracil adducts were studied in the sam e in vivo model. For F-18-FU it was found that the F-18-label tumor ki netics rapidly fell into a biphasic mode: a relatively short F-18 beta phase (F-18 t(1/2) beta 21 +/- 3 min), linked with the total body met abolic capacity and clearance of the animal, and a longer F-18 gamma p hase, linked with the intrinsic intratumoral FU metabolism (Colon 26-1 0: F-18 t(1/2) gamma 10.3 h; Colon 26: F-18 t(1/2) gamma 5.6 h). It is proposed that the observed faster F-18 efflux of the less responsive Colon 26 corresponds to an enhanced breakdown of 5-fluoronucleotides t o 5-fluoronucleosides and subsequent elimination from the tumor cells. It is concluded that on PET scanning, measurement of the dynamic F-18 t(1/2) gamma and F-18 t(1/2) beta parameter is of prime importance fo r an insight in the in vivo tumor biology of a patient.