title: Modification of monoclonal antimyosin antibody: enhanced specificity of localization and scintigraphic visualization in acute experimental myocardial infarction.
abstract: Positively charged polymers have been shown to interact nonselectively with cells in vitro by means of an electrostatic binding to a negatively charged cell surface. We reasoned that, if a net negative charge could be introduced onto an antibody molecule, some of the nonspecific antibody interactions with cells could be avoided without affecting the function of the antibody combining site. An important result would be improved target-to-background ratios should such antibodies be used as in vivo imaging agents. To test this hypothesis, we first reacted bifunctional chelators such as diethylenetriamine pentaacetic acid with cationic polylysine polymers to permit radiolabeling with 111In, then rendered the polymer completely anionic by reacting the residual epsilon amino groups with succinic anhydride. These modified polymers were then covalently linked either to monoclonal antimyosin antibody or to its Fab fragment by means of a water soluble carbodiimide. The immunoreactivity of the antibody-polymer conjugates was not significantly diminished. 111In-labeled antimyosin Fab modified with succinylated polylysine permitted visualization of experimental myocardial infarcts as early as 30 min after intravenous injection. An inverse exponential relationship was observed between the distribution of 201Tl and that of polymer-modified antimyosin Fab. 111In-labeled succinylated polymer administered by itself did not localize in the infarct. These observations suggest that anionically modified antibodies may enhance the specificity of antibody imaging.
authors.affiliation: Cardiac Unit, Massachusetts General Hospital, Boston 02114.
authors.forename: B A
authors.initials: BA
authors.lastname: Khaw
authors.forename: V P
authors.initials: VP
authors.lastname: Torchilin
authors.forename: A L
authors.initials: AL
authors.lastname: Klibanov
authors.forename: N D
authors.initials: ND
authors.lastname: Nossiff
authors.forename: J B
authors.initials: JB
authors.lastname: Powers
authors.forename: H W
authors.initials: HW
authors.lastname: Strauss
authors.forename: E
authors.initials: E
authors.lastname: Haber
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D004285:Dogs; D007205:Indium Radioisotopes; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000378:metabolism; D009218:Myosins / Q000276:immunology / Q000378:metabolism; D004369:Pentetic Acid; D011107:Polylysine; D011877:Radionuclide Imaging
chemical_list: D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D011107:Polylysine; D004369:Pentetic Acid; D009218:Myosins