INTRAVENOUS AND INTRAARTERIAL OXYGEN-15-LABELED WATER AND FLUORINE-18-LABELED FLUOROURACIL IN PATIENTS WITH LIVER METASTASES FROM COLORECTAL-CARCINOMA

Intra-arterial chemotherapy can potentially increase drug delivery at the tumor sites and has therefore been used for the therapy of metasta tic colorectal cancer. Methods: Dynamic PET and [F-18]fluorouracil [F- 18-FU) were used in patients with liver metastases from colorectal can cer to examine the pharmacokinetics of the drug up to 120 min after in travenous and intra-arterial injection of the same dose of fluorouraci l (FU). All patients included in the study (n = 15) had surgically imp lanted catheters in the gastroduodenal artery. Dynamic PET studies (up to 5 min) with O-15-labeled water were performed for the evaluation o f the access to the lesions immediately before the F-18-FU study using both administration routes. The final evaluation included 24 metastas es, obtained from 15 patients. Results: Of 24 lesions, 21 (87.5%) show ed an improved access using the intra-arterial approach, and 20 (83.3% ) demonstrated a better FU influx after intra-arterial F-18-FU infusio n. Metastases reached the highest F-18-FU concentrations after intra-a rterial administration, with a maximum standardized uptake values of 1 8.75 for the FU influx and of 5.03 for FU trapping. Of 24 metastases, eight (33.3%) demonstrated enhanced FU trapping after the intra-arteri al administration, Cluster analysis revealed a group of metastases (n = 6) with a nonperfusion-dependent FU transport using the intravenous application. Of these six lesions, five (83.3%) did not show any enhan cement of the F-18-FU trapping after intra-arterial application. The d ata gave evidence for at least one different, energy-dependent transpo rt system, which can be saturated even after intravenous administratio n of the drug. Conclusion: The data show that the main limiting factor for a therapy response is the very high and rapid elimination of the cytostatic agent out of the tumor cells. Furthermore, it was not possi ble to predict the pharmacokinetics of FU after intra-arterial applica tion using an intravenous PET study. It may be possible, using intrave nous PET double-tracer studies, to identify metastases having a nonper fusion-dependent transport system and exclude them from an intra-arter ial treatment protocol.