Binding properties of 111In-diethylenetriaminepentaacetic acid (DTPA)-fragment E 1,2, a fibrin-specific probe, are dependent on use of protecting complex during attachment of DTPA groups

Abstract

Fragments E 1 and E 2, plasmic degradation products of crosslinked fibrin, bind specifically to polymers of fibrin. A mixture of these fragments, denoted as fragment E 1,2, was radiolabeled with 111In after covalently attaching metal chelating groups (diethylenetriaminepentaacetic acid, DTPA) to the fragment, using two approaches. In the first approach, DTPA groups were attached directly to purified fragment E 1,2. In the second approach, attachment sites of DTPA groups were directed away from the active region of the molecule by having fragment E 1,2 bound in complex, with its active sites protected during the derivatization. Direct attachment of DTPA groups to fragment E 1,2 resulted in complete loss of binding to fibrin in vitro. When derivatized in complex, 111In-DTPA-fragment E 1,2 retained a higher degree of binding to human fragment DD and human plasma clots in vitro than did radioiodinated fragment E 1, even when up to eight DTPA groups were attached per molecule of fragment E 1,2.