Abstract 212: In Vivo Molecular Imaging of Thrombosis and Thrombolysis Using a Fibrin-binding PET Probe

Abstract

Background and purpose: Thrombus formation plays a critical role in cardiovascular diseases, but thrombus imaging is still challenging. Fibrin is a major component of both arterial and venous thrombi, and represents an ideal candidate for molecular imaging of thrombosis. Here, we describe imaging properties and target uptake of a new fibrin-specific PET probe for thrombus detection in two rat models of thrombosis and stroke. Materials and methods: The fibrin-binding probe FBP7 was synthesized by conjugation of the cyclic peptide FHCHypY(3-CI)DLCHIL to a cross-bridge chelator (CB-TE2A), followed by labeling with copper-64. Wistar rats (4-6/group) underwent carotid crush, as a non-occlusive, mural thrombosis model, or embolic stroke as an occlusive clot model followed by thrombolysis. Results: FBP7 clearly detected thrombus location in both animal models, with a high PET target:background ratio that increased over time (>5-fold at 30-90’, >15-fold at 240-300’, Fig. A-B). Biodistribution confirmed the high thrombus uptake (~0.5 %ID/g), which was >5-10 folds greater than blood and other tissues of the head and thorax (C). Similar results were obtained from ex vivo autoradiography of ipsilateral vs. controlateral carotid arteries (D). PET/CT imaging allowed clot localization in the internal carotid/middle cerebral artery (ICA/MCA) segment of all stroke rats. After baseline PET acquisition, animals were infused with tPA (10 mg/kg, i.v.) or vehicle (saline) and imaged again for 90’. Time-dependent reduction of activity at the level of the thrombus was clearly detected in treated rats, but not in vehicle group (E). Brain autoradiography confirmed clot dissolution in tPA-treated animals, but enduring high thrombus activity in ipsilateral ICA/MCA of control rats (F-G). Conclusions: We demonstrated that FBP7 is suitable for molecular imaging of thrombosis and thrombolysis in vivo, and represents a very promising candidate for bench-to-bedside translation.