Intravenous and intra-arterial oxygen-15-labeled water and fluorine-18-labeled fluorouracil in patients with liver metastases from colorectal carcinoma.

UNLABELLED

Intra-arterial chemotherapy can potentially increase drug delivery at the tumor sites and has therefore been used for the therapy of metastatic colorectal cancer.

METHODS

Dynamic PET and [18F]fluorouracil (18F-FU) were used in patients with liver metastases from colorectal cancer to examine the pharmacokinetics of the drug up to 120 min after intravenous and intra-arterial injection of the same dose of fluorouracil (FU). All patients included in the study (n = 15) had surgically implanted catheters in the gastroduodenal artery. Dynamic PET studies (up to 5 min) with 15O-labeled water were performed for the evaluation of the access to the lesions immediately before the 18F-FU study using both administration routes. The final evaluation included 24 metastases, obtained from 15 patients.

RESULTS

Of 24 lesions, 21 (87.5%) showed an improved access using the intra-arterial approach, and 20 (83.3%) demonstrated a better FU influx after intra-arterial 18F-FU infusion. Metastases reached the highest 18F-FU concentrations after intra-arterial administration, with a maximum standardized uptake values of 18.75 for the FU influx and of 5.03 for FU trapping. Of 24 metastases, eight (33.3%) demonstrated enhanced FU trapping after the intra-arterial 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 enhancement of the 18F-FU trapping after intra-arterial application. The data gave evidence for at least one different, energy-dependent transport system, which can be saturated even after intravenous administration 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 possible to predict the pharmacokinetics of FU after intra-arterial application using an intravenous PET study. It may be possible, using intravenous PET double-tracer studies, to identify metastases having a nonperfusion-dependent transport system and exclude them from an intra-arterial treatment protocol.