Chemically optimized antimyosin Fab conjugates with chelating polymers: importance of the nature of the protein-polymer single site covalent bond for biodistribution and infarction localization.

Abstract	Murine antimyosin Fab fragment was conjugated with 111In-labeled N-terminal-modified DTPA-polylysine using three bifunctional reagents: N-hydroxysuccinimide esters of 3-(2-pyridyldithio)propionic acid (SPDP conjugate), 4-(maleimidomethyl)cyclohexanecarboxylic acid (SMCC conjugate) and bromoacetic acid (BrAc conjugate) for potential localization of experimental myocardial infarction. Using various antibody preparations and a rabbit acute myocardial infarction model the following parameters were observed: (1) an in vitro antigen binding activity of SPDP conjugate = SMCC conjugate > BrAc conjugate, (2) a blood clearance rate of SPDP conjugate > BrAc conjugate > SMCC conjugate, (3) a liver and splenic accumulation of SPDP conjugate > BrAc conjugate > SMCC conjugate, and (4) the infarcted tissue activity showed an accumulation of SMCC conjugate > SPDP conjugate > BrAc conjugate. This study exemplifies the importance of rational chemical design of antimyosin Fab-chelating polymer conjugate for improved target tissue localization in vivo.
Authors	V S Trubetskoy, J Narula, B A Khaw, V P Torchilin
Journal	Bioconjugate chemistry (Bioconjug Chem) 1993 Jul-Aug Vol. 4 Issue 4 Pg. 251-5 ISSN: 1043-1802 [Print] United States
PMID	8218480 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antibodies, Monoclonal Chelating Agents Cross-Linking Reagents Immunoglobulin Fab Fragments Indium Radioisotopes Polylysine Pentetic Acid Myosins
Topics	Animals Antibodies, Monoclonal (blood, chemistry) Antibody Specificity Antigen-Antibody Reactions Chelating Agents (chemistry) Cross-Linking Reagents (chemistry) Immunoglobulin Fab Fragments (blood, chemistry) Indium Radioisotopes (blood) Metabolic Clearance Rate Mice Myocardial Infarction (metabolism) Myocardium (metabolism) Myosins (immunology) Pentetic Acid (chemistry) Polylysine (blood, chemistry) Rabbits Tissue Distribution

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