Detection of experimental thrombi in rabbits with an131I-labelled fibrin-specific monoclonal antibody

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Abstract
The detection of thrombi in rabbits has been investigated with131I-labelled DD-3136/22, a monoclonal antibody (Mab) reactive at high affinity (Kd=2.68 x 10−10 M) with human D Dimer (DD). DD-3136/22 bound well to both “fresh” and “aged” human clots in an in vitro assay but showed poor binding to rabbit clots. However, reactivity was restored to rabbit blood if it was seeded, before clotting, with human DD covalently coupled to Sepharose beads. Thus, a rabbit model was developed in which blood was allowed to clot around DD-Sepharose beads introduced into the jugular vein. Gamma camera imaging showed that intact131I-labelled DD-3136/22 localised to these clots within 24 h. Uptake at this time was 0.202±0.012% injected dose per gram (%ID/g) compared with 0.086±0.018%ID/g after injection of control antibody.131I-labelled F(ab′)2, fragments of DD-3136/22 allowed earlier scintigraphic detection of the clot which was evident 4 h after injection. Uptake in the clot at 24 h was 0.154±0.038 %ID/g compared with 0.109±0.027 %ID/g for a control F(ab')2. As antigen levels in the clot are estimated to be less than 300 μg DD, thus representing a very small human clot, the DD-3136/22 Mab would appear to have a good potential for the sensitive detection of thrombi in a clinical setting.