Intravitalmikroskopische und pharmakokinetische Untersuchung zur Anreicherung von 5-FU-PEG-Liposomen sowie dynamisches MRT-Monitoring des Langzeitverlaufs an CC-531 lebertumortragenden WAG-Ratten

Abstract

Controversy still exists for therapy of inoperable colorectal liver metastases. Regional therapy has been considered a promising approach because several clinical studies demonstrated prolonged survival. The aim of this study was to investigate tumor targeting of the most frequently used cytostatic 5-fluouracil by modifying systemic and regional therapy by liposome encapsulation. Our results demonstrate that encapsulation of 5-FU in SUV-PEG liposomes increased tumor concentration by the factor 25 fold with systemic and factor 85 with regional therapy. Reduction of blood flow by starch microspheres (SMS) during regional chemotherapy with liposome-encapsuled 5-FU resulted in an additional 4000 fold increase in 5-FU tumor concentration.

Long-term results showed that 5FU-PEG liposomes + SMS led to a 50% tumor recurrence 2 weeks after therapy, while there was a 10- to 19-fold tumor increase in the i.v. groups.

These results are substantiated by intravital microscopy which revealed the highest fluorescence in tumor tissue in the group receiving 5FU-PEG liposomes/starch microspheres.