Enhanced Accumulation of Long-circulating Liposomes Modified with the Nucleosome-specific Monoclonal Antibody 2C5 in Various Tumours in Mice: Gamma-imaging Studies

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2006 Jun 10

PMID 16763815

Citations 34

Authors

Tamer A Elbayoumi

Vladimir P Torchilin

Affiliations

Soon will be listed here.

Abstract

Purpose: 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.

Conclusion: 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.

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