N. Oku et al., REAL-TIME ANALYSIS OF LIPOSOMAL TRAFFICKING IN TUMOR-BEARING MICE BY USE OF POSITRON EMISSION TOMOGRAPHY, Biochimica et biophysica acta. Biomembranes, 1238(1), 1995, pp. 86-90
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.