AHA Journals, Author Interviews, Blood Clots, Brigham & Women's - Harvard, Medical Imaging / 17.09.2015

Peter Caravan, PhD Co-Director, Institute for Innovation in Imaging (I3) Martinos Center for Biomedical Imaging Massachusetts General Hospital Associate Professor of Radiology Harvard Medical SchoolMedicalResearch.com Interview with: Peter Caravan, PhD Co-Director, Institute for Innovation in Imaging (I3) Martinos Center for Biomedical Imaging Massachusetts General Hospital Associate Professor of Radiology Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Caravan: The motivation for this work was to develop a technique that would allow the detection of thrombus (clot) anywhere in the body after injection of a molecular probe called 64Cu-FBP8.  Current techniques for thrombus detection are limited to specific vascular territories.  In instances where the location of the thrombus is unknown or if there is suspicion of multiple thrombi, then multiple imaging tests must be performed.  We sought to develop a test that could be used to find clots anywhere:  brain, thorax, abdomen, legs and in arteries, veins, or the cardiac chambers.  In addition to whole body thrombus detection, we sought a technique that could address some of the limitations with current thrombus imaging techniques.  For example computed tomography (CT), which is used to detect pulmonary emboli, requires a contrast agent that cannot be used in patients with poor kidney function.  Transesophageal echocardiography used to identify thrombus in the chambers of the heart requires that the patient be sedated. Our approach is to use a small peptide that recognizes the protein fibrin, which is a key component of blood clots.  We tagged the peptide with an isotope of copper, Cu-64, that allows the peptide to be detected by positron emission tomography (PET). 64Cu-FBP8 binds specifically to fibrin but not to other proteins in the blood and this means that the uptake in the clot is high while background signal is very low.  We combined PET imaging which finds the clot with CT imaging or magnetic resonance imaging (MRI).  By overlaying the PET image with the CT or MRI image, we could precisely localize the clot within the We were interested to see if the age of the clot impacted our ability to detect it.  We imaged animals with a total of 42 arterial or venous clots and then the images were analyzed by two reviewers who had no prior knowledge of the location of the clot.  Overall the accuracy was 98% for detection. Another key finding was that the uptake of 64Cu-FBP8 strongly correlated with the amount of fibrin in the clot and that younger, fresher clots had more fibrin than older clots.  This could be very useful in distinguishing newer clots which may be the source of cardiovascular events from older, clots that may pose less risk. We also showed using combined PET-MRI that we could detect multiple blood clots in the animal in a single whole body scan.  The procedure involves a single intravenous administration of 64Cu-FBP8 and clots in the deep veins of the legs or in the carotid arteries were readily detected. (more…)