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Am J Physiol Lung Cell Mol Physiol 261: L60-L65, 1991;
1040-0605/91 $5.00
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Targeting of macromolecular carriers and liposomes by antibodies to myosin heavy chain

Alexander L. Klibanov 1, Ban An Khaw 1, Naseem Nossiff 1, Sean M. O'Donnell 1, Leaf Huang 1, Mikhail A. Slinkin 1, and Vladimir P. Torchilin 1

1 Institute of Experimental Cardiology, 121552 Moscow, USSR; Division of Nuclear Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; and Department of Biochemistry, University of Tennessee, Knoxville, Tennessee 37996-0840

Macromolecular carriers and liposomes were covalently coupled to monoclonal antibodies against cardiac myosin heavy chain. Deferoxamine-modified polymers bound tightly with 67Ga and 68Ga radioisotopes. Ternary deferoxamine-polylysine antibody conjugates specifically targeted the radioisotopes to a myosin-coated microplate. Scatchard analysis revealed a high affinity of the conjugate for the target with a Kas of ap108 M–1. Liposomes that contained immobilized antimyosin antibodies were targeted specifically to the myosin-coated plate. Additional coating of these liposomes with polyethylene glycol reduced specific binding to the target in vitro. However, because of the presence of polyethylene glycol on the surface of liposomes, these liposomes had a long half-life and slowly cleared from the bloodstream after intravenous injection. These immunoliposomes showed up to 16- to 18-fold specific localization to the necrotic areas of the myocardium in rabbits with experimental infarction.

antimyosin; chelating polymer; liposome; monoclonal antibody; myocardial infarction; radioimmunoimaging







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