Imaging thrombi with radiolabelled fragment E1.

Abstract

Fragment E1 is a fragment of human fibrin, produced by controlled plasmin digestion of cross-linked fibrin. It comprises the N-terminal regions of all six polypeptide chains of fibrin. It has been shown to contain a pair of dimeric binding sites which are complementary in binding to sites in the D domains of fibrin which are formed when fibrin polymerizes, so fragment E1 binds to fibrin dimers and polymers but not fibrin monomer or fibrinogen. Radioiodinated fragment E1 has been shown to localize in venous thrombi in a pig model. Thrombus/blood ratios of up to 100: 1 were obtained at 24 h post injection, in thrombi up to 5 days old at the time of tracer injection. In humans, deep-venous thrombi were visualized within 30 min of 123I-labelled fragment E1. Fragment E1 exhibits very rapid blood disappearance, which enhances its ability to produce high thrombus/blood ratios at early times. The thrombus uptake of labelled fragment E1 is not affected by heparin. Fragment E1 has been derivatized with metal chelating groups [diethylene-triaminepentaacetic acid (DTPA) and deferoxamine], to facilitate labelling with 111In and 67Ga. Although these labels appeared promising in animal models, they have not yet achieved success in man. Clinical trials are continuing with 123I-labelled fragment E1, which is felt to be a most promising radiopharmaceutical for thrombus localization.