Thrombus radioimmunoscintigraphy: an approach using monoclonal antiplatelet antibody

Thrombus detection and localization is of cardinal importance in clinical medicine. The currently available method using autologous 111In-labeled platelets is too lengthy and complex for everyday use. It requires careful separation of the platelets prior to labeling and visualization of the thrombus becomes possible only 24 hr after injection. An approach to thrombus imaging using a monoclonal antiplatelet antibody labeled with 111In or 123I is described. The antibody (7E3) prepared against human platelets inhibits the interaction between fibrinogen-coated beads and both human and dog platelets. 7E3 is an IgG1 that binds to the complexed glycoprotein IIb/IIIa. Ninety percent of a tracer dose of radiolabeled 7E3 binds to human platelets and 50% binds to dog platelets. In vitro studies showed that virtually all of the platelet-bound radioactivity becomes incorporated into clots formed by adding thrombin to whole blood. 7E3 was labeled with 111In by the cyclic anhydride diethylenetriaminepentaacetic acid method or by radioiodination with 123I. At a ratio of 1:50 (anhydride:7E3) the specific activity ranged between 10 and 40 muCi/micrograms (1 Ci = 37 GBq) without change in the antibody characteristics. In vivo studies in dogs were performed by preincubating for 1 hr the radiolabeled 7E3 with citrated blood or by directly injecting the radiolabeled 7E3 intravenously. Experimental thrombi were induced by transcatheter placement of copper coils into peripheral arteries and veins as well as in the superior vena cava and pulmonary artery. With gamma camera, visualization of venous and arterial thrombi as well as sites of intimal injury without visible thrombi, could be observed 1-1.5 hr after injection. There was no need for delayed imaging because of the fast clearance of radioactivity from the circulation nor was there need for blood pool subtraction. Two to 10-hr thrombi could be imaged but 48-hr thrombi were not detectable with this method. No change in platelet counts before and after the injection of labeled 7E3 nor increased bleeding tendency occurred. The advantages of this method are a shorter preimaging preparation time, faster visualization after injection, and no need for delayed imaging or subtraction techniques. For these reasons human investigations seem to be warranted.