title: In vitro and in vivo study of 99mTc-MIBI encapsulated in PEG-liposomes: a promising radiotracer for tumour imaging.
abstract: Encapsulation of technetium-99m sestamibi ((99m)Tc-MIBI) in polyethyleneglycol-liposomes ((99m)Tc-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 (99m)Tc-MIBI in PEG-liposomes is described. The (99m)Tc-MIBI-PEG-liposomes were compared with free (99m)Tc-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/PEG(2000)-distearoyl phosphatidylethanolamine and lissamine-rhodamine B-labelled liposomes were used. The encapsulation of (99m)Tc-MIBI in liposomes was achieved using the K(+) diffusion potential method. We compared the uptake of free versus encapsulated (99m)Tc-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 (99m)Tc-MIBI encapsulation in PEG-liposomes was 50+/-5%. Use of (99m)Tc-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 (99m)Tc-MIBI, whereas activity of free (99m)Tc-MIBI in kidneys and bladder was markedly higher than that of encapsulated (99m)Tc-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 (99m)Tc-MIBI. Summarising, the (99m)Tc-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. (99m)Tc-MIBI-PEG-liposomes therefore show promising potential for tumour imaging.
authors.affiliation: Laboratoire de radiopharmacologie et traitement de l'image, UPRES 2360, Université de Paris Nord, 74 rue Marcel Cachin, 93017 Bobigny cedex, France.
authors.forename: Hayet
authors.initials: H
authors.lastname: Belhaj-Tayeb
authors.forename: Dominique
authors.initials: D
authors.lastname: Briane
authors.forename: Jackie
authors.initials: J
authors.lastname: Vergote
authors.forename: Suchart
authors.initials: S
authors.lastname: Kothan
authors.forename: Gérard
authors.initials: G
authors.lastname: Léger
authors.forename: Saad-Eddine
authors.initials: SE
authors.lastname: Bendada
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Tofighi
authors.forename: Feyzi
authors.initials: F
authors.lastname: Tamgac
authors.forename: An
authors.initials: A
authors.lastname: Cao
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Moretti
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000000981:diagnostic imaging / Q000378:metabolism*; D008081:Liposomes / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D011092:Polyethylene Glycols; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017256:Technetium Tc 99m Sestamibi / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014915:Whole-Body Counting
chemical_list: D020099:Coated Materials, Biocompatible; D008081:Liposomes; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols; D017256:Technetium Tc 99m Sestamibi