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

Murine antimyosin Fab fragment was conjugated with In-111-labeled N-te rminal-modified DTPA-polylysine using three bifunctional reagents: N-h ydroxysuccinimide esters of 3-(2-pyridyldithio)propionic acid (SPDP co njugate), 4-(maleimidomethyl)cyclohexanecarboxylic acid (SMCC conjugat e) and bromoacetic acid (BrAc conjugate) for potential localization of experimental myocardial infarction. Using various antibody preparatio ns and a rabbit acute myocardial infarction model the following parame ters were observed: (1) an in vitro antigen binding activity of SPDP c onjugate = 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 conjuga te, and (4) the infarcted tissue activity showed an accumulation of SM CC 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.