DEGREE OF POLYMER ORGANIZATION DECREASES THE BINDING OF A MONOCLONAL-ANTIBODY RAISED AGAINST THE BETA-CHAIN AMINO-TERMINUS OF FIBRIN

Accurate non-invasive diagnosis of deep venous thrombosis and pulmonar y embolism remains an elusive goal, Radiolabeled antibodies specific f or the epitope exposed on the beta-chain of fibrin after fibrinopeptid e B release (anti-beta) enabled hi situ imaging of thrombi in experime ntal subjects with nuclear medicine techniques. When used in patients anticoagulated for thrombo-embolic disease, however, the antibody was unable to reliably image the thrombi, We postulated that the neoepitop e on the beta-chain of fibrin is covered up as fibrin organizes into a polymer network and is therefore exposed to the antibody only during active incorporation of fibrin subunits. We determined the equilibrium binding kinetics of an anti-beta monoclonal antibody to fibrin in var ious stages of organization. The concentration of exposed epitopes on immobilized fibrin monomers was equal to the molar concentration of fi brin beta-chains. The percentage of beta-chains exposed to the antibod ies markedly decreased as the fibrin network was allowed to organize, a process catalyzed by calcium. Conclusions: The beta-chain amino term inus of fibrin is exposed transiently as subunits are added to the enl arging fibrin network. Anti-beta antibodies bind preferentially to act ively enlarging fibrin polymers.