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The activated platelet is a potential target for the localization of thrombi in vivo since, after stimulation and secretion of granule contents, activated platelets are concentrated at sites of blood clot formation. In this study, wefised antibodies specific for a membrane protein of activated plate, lets to detect experimental thrombi in an animal model. PADGEM (platelet activation-dependent granule-external membrane protein), a platelet a-granule membrane protein, is translocated to the plasma membrane during platelet activation and granule secretion. Since PADGEM is-internal in unstimulated platelets, polyclonal anti-PADGEM and monoclonal KC4 antibodies do not bind to circulating resting platelets but do interact with activated platelets. Dacron graft material incubated with radiolabeled KC4 or anti-PADGEM antibodies in the presence of thrombin-activated platelet-rich plasma bound most of the antibody. Imaging experiments with 123I-labeled anti-PADGEM in baboons with an external arterialvenous Dacron shunt revealed rapid uptake in the thrombus induced by the Dacron graft; control experiments with 'DIlabeled nonimmune IgG exhibited minimal uptake. Deep venous thrombi, formed by using percutaiieous balloon catheters to stop blood flow in the femoral vein of baboons, were visualized with 123I-labeled anti-PADGEM. Thrombi were discernible against blood pool background activity without subtraction techniques within 1 hr. No target enhancement was seen with 1231-labeled nonimmune IgG. 123I-labeled anti-PADGEM cleared the blood pool with an initial halfdisappearance time of 6 min and did not interfere with hemostasis. These results indicate that radioimmunoscintigraphy with anti-PADGEM antibodies can visualize thrombi in baboon models and is a promising technique for clinical thrombus detection in humans.

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