REAL-TIME ANALYSIS OF LIPOSOMAL TRAFFICKING IN TUMOR-BEARING MICE BY USE OF POSITRON EMISSION TOMOGRAPHY

Long-circulating liposomes are known to accumulate passively in tumor tissues of tumor-bearing animals, To evaluate the in vivo behavior of such liposomes, we investigated the real-time liposomal trafficking by a non-invasive method using positron emission tomography (PET), Lipos omes composed of dipalmitoylphosphatidylcholine, cholesterol, and palm ityl-D-glucursoide (PGlcUA) in a molar ratio of 4:4:1 were prepared in the presence of 2-[F-18]fluoro-2-deoxyglucose ([2-F-18]FDG). [2-F-18] FDG-labeled liposomes sized by extrusion through a filter with various -sized pores were administered to mice bearing Meth A sarcoma, and a P ET scan was performed for 120 min. Small-sized, long-circulating lipos omes (100 nm in diameter) constructed with PGlcUA tended to accumulate in the tumor tissues. On the contrary, control liposomes (100 nm in d iameter) containing dipalmitoylphosphatidylglycerol instead of PGlcUA accumulated in the liver. Large-sized PGlcUA-containing liposomes (> 3 00 nm) also accumulated in the liver, as well as in the spleen. Time-a ctivity curves indicated that the small long-circulating liposomes (< 200 nm) transiently accumulated in the liver right after the injection but that the accumulation there decreased time-dependently, These dat a suggest that, although the majority of small long-circulating liposo mes remain in the bloodstream, some extravasate once into the intersti tial spaces in the liver re-enter the bloodstream again, and finally a ccumulate in the tumor tissues. This PET technique might be useful for studying real-time liposomal trafficking and for tumor imaging.