Various kinds of long-circulating
liposome, such as
ganglioside GM1-, polyethyleneglycol- (PEG-), and
glucuronide-modified
liposomes, have been developed for passive targeting of liposomal drugs to tumours. To evaluate the in vivo behaviour of such long-circulating
liposomes, we investigated the liposomal trafficking, especially early trafficking just after injection of
liposomes, by a non-invasive method using positron emission tomography (PET).
Liposomes composed of
dipalmitoylphosphatidylcholine,
cholesterol, and modifier, namely, GM1, distearoylphosphatidylethanolamine (
DSPE)-PEG or palmityl-D-
glucuronide (
PGlcUA), were labelled with [2-18F]-
2-fluoro-2-deoxy-D-glucose ([2-18F]FDG), and administered to mice bearing Meth A
sarcoma after having been sized to 100 nm. A PET scan was started immediately after injection of
liposomes and continued for 120 min. PET images and time-activity curves indicated that PEG
liposomes and
PGlcUA liposomes were efficiently accumulated in tumour tissues time dependently from immediately after injection. In contrast, GM1
liposomes accumulated less in the tumour as was also the case for control
liposomes that contained
dipalmitoylphosphatidylglycerol (
DPPG) instead of a modifier. Long-circulating
liposomes including GM1
liposomes, however, remained in the blood circulation and avoided liver trapping compared with control
DPPG liposomes. These data suggest that
PGlcUA and PEG
liposomes start to accumulate in the tumour just after injection, whereas GM1
liposomes may accumulate in the tumour after a longer period of circulation.