Monoclonal antibody modification with chelate-linked high-molecular-weight polymers: major increases in polyvalent cation binding without loss of antigen binding.
Polyethyleneimine or polylysines of differing molecular sizes were substituted with either EDTA or DTPA and then with succinic acid groups. These polymers were then reacted with the amino groups on myosin-specific monoclonal antibody or its Fab using a water soluble carbodiimide. The polymer-antibody complexes were capable of binding up to 150 di- or trivalent ions per mole (Mn++, Gd , or 111In ) without attendant loss of antigen binding. The polylysine derivatives of the intact antibody were rapidly cleared and sequestered in the liver, whereas the polylysine 14-kilodalton (kd) derivative of Fab was cleared from the circulation with minimal hepatic and kidney sequestration. This differed from the biodistribution of intact antimyosin or its Fab labeled with 111In via direct attachment of DTPA to the epsilon amino group of the lysyl residues. Applications in magnetic resonance and nuclear imaging are envisioned.
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D004492:Edetic Acid; D007204:Indium; D007700:Kinetics; D004369:Pentetic Acid; D011094:Polyethyleneimine; D011095:Polyethylenes; D011107:Polylysine; D011485:Protein Binding; D011868:Radioisotopes; D013386:Succinates
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D011095:Polyethylenes; D011868:Radioisotopes; D013386:Succinates; D007204:Indium; D011107:Polylysine; D004369:Pentetic Acid; D011094:Polyethyleneimine; D004492:Edetic Acid