Enhanced accumulation of long-circulating liposomes modified with the nucleosome-specific monoclonal antibody 2C5 in various tumours in mice: gamma-imaging studies.
OBJECTIVE
To further improve tumour targeting and delivery of imaging agents by long-circulating liposomes via the coupling of the anti-cancer monoclonal antibody 2C5 with nucleosome-restricted activity, which can recognize the surface of various tumours but not normal cells and can specifically target pharmaceutical carriers to tumour cells in vitro and in vivo.


METHODS
The 2C5 antibody was attached to the surface of long-circulating PEG-liposomes (LCL) by the post-insertion technique after antibody modification with a single-terminus activated PEG-lipid derivative to yield nucleosome-specific tumour-targeted liposomes. Tumour cell binding of the targeted liposomes was verified both by fluorescence microscopy and by flow cytometry in several cell lines using fluorescently labelled liposomes. 111In-radiolabelled liposomal formulations (prepared using membrane-anchored chelating groups) were used to examine in vivo biodistribution and tumour accumulation of liposomes by direct gamma scintigraphy.


RESULTS
The 2C5 antibody-modified LCL demonstrated a three- to eightfold increase in in vitro specific cell binding to various cancer cell lines of diverse origin. 111In-labelled tumour-targeted liposomes demonstrated prolonged circulation and doubled tumour accumulation compared with that of control formulations. Whole-body gamma scintigraphic imaging of mice implanted with different tumours revealed markedly faster (6 h post injection for 2C5-LCL vs 24 h for non-specific analogues) and superior in vivo tumour visualization with 111In-2C5-LCL than with the 2C5-free formulations in tested tumour models.


CONCLUSIONS
The 2C5 antibody-modified LCL effectively and specifically accumulate in various tumours and can serve as delivery vehicles for imaging agents, allowing for fast and efficient tumour visualization.
Elbayoumi
Tamer A
TA
Department of Pharmaceutical Sciences, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, Boston, MA 02115, USA.
Torchilin
Vladimir P
VP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D009707:Nucleosomes / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D009928:Organ Specificity; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D008081:Liposomes; D009707:Nucleosomes