Published online before print August 8, 2002, doi: 10.1161/01.ATV.0000033089.56970.2D
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© 2002 American Heart Association, Inc.
Thrombosis |
In Vivo Imaging of Thrombin Activity in Experimental Thrombi With Thrombin-Sensitive Near-Infrared Molecular Probe
From the Center for Molecular Imaging Research (F.A.J., C.-H.T., R.W.) and the Center for Immunology and Inflammatory Diseases (R.E.G.), Massachusetts General Hospital, Harvard Medical School, Charlestown, and the Cardiology Division (F.A.J., R.E.G.), Department of Medicine, Massachusetts General Hospital, Boston.
Correspondence to Farouc A. Jaffer, MD, PhD, Center for Molecular Imaging Research, Massachusetts General Hospital, 149 13th St, Room 5406, Charlestown, MA 02129. E-mail fjaffer{at}partners.org
Objective— Thrombin, a serine protease, plays an important role in thrombosis as well as other cellular and developmental processes. In this study, we investigated the ability of a novel thrombin-activatable molecular probe to provide in vivo images of thrombin activity in experimental thrombi.
Methods and Results— The thrombin probe consists of a near-infrared (NIR) fluorochrome attached to a delivery vehicle via a thrombin-specific oligopeptide substrate. In human blood, endogenous thrombin activated the thrombin probe and increased the fluorescence signal by 18-fold (P=0.008). Hirudin, a specific thrombin inhibitor, suppressed probe activation by 82% (P=0.007). Imaging of in vivo thrombin activity was then investigated in acute experimental murine thrombosis models up to 12 hours. After systemic thrombin probe injection, focal NIR fluorescence signal enhancement was rapidly detected within acute and subacute thrombi. In contrast, no thrombosis signal enhancement was seen in similar experiments with a control NIR fluorochrome.
Conclusions— Thrombin activity can be imaged in vivo by using a novel thrombin-activatable and thrombin-specific NIR molecular probe. The thrombin probe could enhance the understanding of the role of thrombin in thrombogenesis and other homeostatic and pathological conditions.
Key Words: thrombin • near-infrared imaging • optical fluorescence • molecular imaging • thrombosis
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