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 position emission tomography (PET).
Liposomes composed of
dipalmitoylphosphatidylcholine,
cholesterol, and palmityl-D-
glucuronide (
PGlcUA) in a molar ratio of 4:4:1 were prepared in the presence of 2-[18F]fluoro-
2-deoxyglucose ([2-18F]FDG). [2-18F]FDG-labeled
liposomes sized by extrusion through a filter with various-sized pores were administered to mice bearing Meth A
sarcoma, and a PET scan was performed for 120 min. Small-sized, long-circulating
liposomes (100 nm in diameter) constructed with
PGlcUA tended to accumulate in the
tumor tissues. On the contrary, control
liposomes (100 nm in diameter) containing
dipalmitoylphosphatidylglycerol instead of
PGlcUA accumulated in the liver. Large-sized
PGlcUA-containing
liposomes (> 300 nm) also accumulated in the liver, as well as in the spleen. Time-activity 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 data suggest that, although the majority of small long-circulating
liposomes remain in the bloodstream, some extravasate once into the interstitial spaces in the liver re-enter the bloodstream again, and finally accumulate in the
tumor tissues. This PET technique might be useful for studying real-time liposomal trafficking and for
tumor imaging.