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Exploratory Development of Molecular Magnetic Resonance Imaging Targeting P-selectin in Early Diagnosis of Thrombosis
Ya-Peng Zhao#, Pei-Pei Jin1#, Tong Zhou*, Xue-Feng Wang1, Gao-Ren Zhong2, Xiao Li, Ming-Jung Zhang, Nan Chen, Hong-Li Wang1
Department of Nephrology, 1Department of Clinical Transfusion, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; 2Department of Radiopharmacy, School of Pharm
Abstract: Thrombotic disease is a clinically common disease involving various organs that is associated with vessel injury， blood constituent alteration and the local stasis of blood flow. P-selectin， an activation marker and adhesive receptor of platelets and endothelial cells， takes part in the initiation of thrombosis， and links inflammation with thrombosis as an important mediator and target molecule. Accordingly， we tried to use molecular magnetic resonance imaging (MRI) with a P-selectin targeted contrast agent to diagnose thrombosis in the early phase. The P-selectin-targeted contrast agent was developed by conjugating anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) which was prepared by our lab. We investigated the potential of this contrast agent using in vitro molecular imaging experiment as well as in vivo experiment in a dog model of venous thrombosis. The results indicated that the imaging signals were enhanced by the P-selectin-targeted contrast agent both in platelet-thrombosis and whole blood-thrombosis in vitro. Further study showed that， P-selectin was expressed immediately in tunica intima of injured vein and subsequently in thrombus after the model established. Correspondingly， mural thrombus showed higher signal visualization than surrounding muscle 30 min after contrast agent injection. These enhanced signals exhibited P-selectin specificity and persisted from the initiation of intima lesions to 3 h after development of thrombosis. The same results were derived from 30 min to 4 h after contrast agent being injected in distal to heart part of the injured vessel， and the signal decreased 24 h later. Moreover， the contrast agent did not affect the vital signs of the dog and the heart， lung， liver and kidney functions remained normal after contrast administration. In conclusion， our results suggested that the new prepared MR contrast agent exhibited high specific binding to P-selectin， and can be used to locate thrombus and reflect the status of thrombosis in the early stage in vivo. In addition， this contrast agent did not compromise the function of the important organs. Our study established a new feasible method for early diagnosis of thrombosis.
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