IN-VIVO TRAFFICKING OF LONG-CIRCULATING LIPOSOMES IN TUMOR-BEARING MICE DETERMINED BY POSITRON EMISSION TOMOGRAPHY

Various kinds of long-circulating liposome, such as ganglioside GM1-, polyethyleneglycol- (PEG-), and glucuronide-modified liposomes, have b een 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 j ust after injection of liposomes, by a non-invasive method using posit ron emission tomography (PET). Liposomes composed of dipalmitoylphosph atidylcholine, cholesterol, and modifier, namely, GM1, distearoylphosp hatidylethanolamine (DSPE)-PEG or palmityl-D-glucuronide (PGlcUA), wer e labelled with [2-F-18]-2-fluoro-2-deoxy-D-glucose ([2-F-18]FDG), and administered to mice bearing Meth A sarcoma after having been sized t o 100nm. A PET scan was started immediately after injection of liposom es and continued for 120 min. PET images and time-activity curves indi cated that PEG liposomes and PGlcUA liposomes were efficiently accumul ated in tumour tissues time dependently from immediately after injecti on. In contrast, GM1 liposomes accumulated less in the tumour as was a lso the case for control liposomes that contained dipalmitoylphosphati dylglycerol (DPPG) instead of a modifier. Long-circulating liposomes i ncluding GM1 liposomes, however, remained in the blood circulation and avoided liver trapping compared with control DPPG liposomes. These da ta suggest that PGlcUA and PEG liposomes start to accumulate in the tu mour just after injection, whereas GM1 liposomes may accumulate in the tumour after a longer period of circulation.