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

Bioconjug Chem. 1993 Jul-Aug;4(4):251-5. doi: 10.1021/bc00022a001.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / chemistry*
  • Antibody Specificity
  • Antigen-Antibody Reactions
  • Chelating Agents / chemistry
  • Cross-Linking Reagents / chemistry
  • Immunoglobulin Fab Fragments / blood
  • Immunoglobulin Fab Fragments / chemistry*
  • Indium Radioisotopes / blood
  • Metabolic Clearance Rate
  • Mice
  • Myocardial Infarction / metabolism*
  • Myocardium / metabolism
  • Myosins / immunology*
  • Pentetic Acid / chemistry
  • Polylysine / blood
  • Polylysine / chemistry
  • Rabbits
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Chelating Agents
  • Cross-Linking Reagents
  • Immunoglobulin Fab Fragments
  • Indium Radioisotopes
  • Polylysine
  • Pentetic Acid
  • Myosins