WP3.2 A novel contrast agent for detecting active thrombus formation in vivo

Work package 3.2
WP3.2 A novel contrast agent for detecting active thrombus formation in vivo

Early detection and fibrinolytic therapy of thrombus formation is crucial for prevention and treatment of stroke. Non-invasive molecular detection of fresh thrombi can greatly aid in localizing sites of occlusion and in clinical descision making. We have shown that bimodal contrast agent A14 can visualize thrombus formation seconds after induction, both in vitro and in vivo (in the mouse). Imaging was specific for fresh thrombi as older thrombi (>24h) were not detected. We will assess and optimize the affinity and specificity of A14-variants and make them suitable for large scale production. We will evaluate the modified peptide in animal studies and prepare for a proof of concept study in men.

Figure: Bimodal molecular imaging of thrombi with A14-DTPA-Gd-rhodamine. Yellow arrows indicate positive in vivo magnetic resonance imaging (MRI) intensity of an FeCl3-induced carotid artery thrombus. Two-photon laser scanning microscopy (TPLSM) reveals elongated smooth muscle cells of the vessel wall (green) together with leucocytes (green) captured in the thrombus visible by covalent attachment of the (red) A14-DTPA-Gd-rhodamine imaging agent.

Work package leader(s): 
Peter Timmerman, Prof. dr.
Tilman Hackeng, Prof. dr.
28/11/2014