In vitro and in vivo study of 99mTc-MIBI encapsulated in PEG-liposomes: a promising radiotracer for tumour imaging.

Encapsulation of technetium-99m sestamibi (99mTc-MIBI) in polyethyleneglycol-liposomes (99mTc-MIBI-PEG-liposomes) could extend the duration of its circulation in blood and alter its biodistribution, enabling its concentration in tumours to be increased. An original method to encapsulate 99mTc-MIBI in PEG-liposomes is described. The 99mTc-MIBI-PEG-liposomes were compared with free 99mTc-MIBI with respect to (a) tumour availability (b) ability to distinguish between chemotherapy-sensitive and -resistant cells and (c) uptake ratio in tumour imaging. PEG-liposomal systems composed of distearoylphosphatidylcholine/cholesterol/PEG2000-distearoyl phosphatidylethanolamine and lissamine-rhodamine B-labelled liposomes were used. The encapsulation of 99mTc-MIBI in liposomes was achieved using the K+ diffusion potential method. We compared the uptake of free versus encapsulated 99mTc-MIBI by sensitive and resistant erythroleukaemia (K562) and breast tumour (MCF-7ras) cells. To assess the internalisation of these liposomes into cells, rhodamine B-labelled PEG-liposomes were used and visualised by fluorescence microscopy. Biodistribution and imaging characteristics of encapsulated and free radiotracer were determined in rats and tumour-bearing nude mice. The efficiency of 99mTc-MIBI encapsulation in PEG-liposomes was 50±5%. Use of 99mTc-MIBI-PEG-liposomes did not impair the ability of this tracer to distinguish between chemotherapy-sensitive and -resistant tumour cells; the percentage of radioactivity accumulated in the sensitive K562 cells was 1.24±0.04%, as compared with 0.41±0.04% in the resistant K562 cells. One hour post injection in rats, PEG-liposomes showed a ten times higher activity in blood than free 99mTc-MIBI, whereas activity of free 99mTc-MIBI in kidneys and bladder was markedly higher than that of encapsulated 99mTc-MIBI, indicating faster clearance of the free radiotracer. In the (MCF7-ras)-bearing nude mice, PEG-liposome uptake in tumour was two times that of free 99mTc-MIBI. Summarising, the 99mTc-MIBI-PEG-liposomes demonstrated a longer blood circulation time, enabled distinction between chemotherapy-sensitive and -resistant cells and improved tumour to background contrast in in vivo imaging. 99mTc-MIBI-PEG-liposomes therefore show promising potential for tumour imaging.