N. Oku et al., IN-VIVO TRAFFICKING OF LONG-CIRCULATING LIPOSOMES IN TUMOR-BEARING MICE DETERMINED BY POSITRON EMISSION TOMOGRAPHY, Biopharmaceutics & drug disposition, 17(5), 1996, pp. 435-441
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.