Peter Caravan1,2, Ilknur Ay1, David Izquierdo-Garcia1,3, Himashinie Diyabalanage4, Ian A Ramsay1,4,2, Nicholas J Rotile1,2, Adam Mauskapf5, Ji-Kyung Choi1, Thomas Witzel1, Valerie Humblet4, Farouc A Jaffer5, Anna-Liisa Brownell6, Ahmed Tawakol7, Ciprian Catana1,2, Mark F Conrad8. 1. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (D.I.-G., I.A.R., N.J.R., J.-K.C., T.W., C.C., P.C., I.A.), Massachusetts General Hospital and Harvard Medical School, Charlestown. 2. The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown (I.A.R., N.J.R., C.C., P.C.). 3. Harvard-MIT Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge (D.I.-G.). 4. Collagen Medical, LLC, Belmont, MA (H.D., I.A.R., V.H.). 5. Cardiovascular Research Center, Division of Cardiology, Department of Medicine (A.M., F.A.J.), Massachusetts General Hospital and Harvard Medical School, Boston. 6. Gordon Center for Medical Imaging, Department of Radiology (A.-L.B.), Massachusetts General Hospital and Harvard Medical School, Charlestown. 7. Nuclear Cardiology, Division of Cardiology, Department of Medicine (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston. 8. Division of Vascular and Endovascular Surgery (M.F.C.), Massachusetts General Hospital and Harvard Medical School, Boston.
Abstract
BACKGROUND AND PURPOSE: High-risk atherosclerosis is an underlying cause of cardiovascular events, yet identifying the specific patient population at immediate risk is still challenging. Here, we used a rabbit model of atherosclerotic plaque rupture and human carotid endarterectomy specimens to describe the potential of molecular fibrin imaging as a tool to identify thrombotic plaques. METHODS: Atherosclerotic plaques in rabbits were induced using a high-cholesterol diet and aortic balloon injury (N=13). Pharmacological triggering was used in a group of rabbits (n=9) to induce plaque disruption. Animals were grouped into thrombotic and nonthrombotic plaque groups based on gross pathology (gold standard). All animals were injected with a novel fibrin-specific probe 68Ga-CM246 followed by positron emission tomography (PET)/magnetic resonance imaging 90 minutes later. 68Ga-CM246 was quantified on the PET images using tissue-to-background (back muscle) ratios and standardized uptake value. RESULTS: Both tissue-to-background (back muscle) ratios and standardized uptake value were significantly higher in the thrombotic versus nonthrombotic group (P<0.05). Ex vivo PET and autoradiography of the abdominal aorta correlated positively with in vivo PET measurements. Plaque disruption identified by 68Ga-CM246 PET agreed with gross pathology assessment (85%). In ex vivo surgical specimens obtained from patients undergoing elective carotid endarterectomy (N=12), 68Ga-CM246 showed significantly higher binding to carotid plaques compared to a D-cysteine nonbinding control probe. CONCLUSIONS: We demonstrated that molecular fibrin PET imaging using 68Ga-CM246 could be a useful tool to diagnose experimental and clinical atherothrombosis. Based on our initial results using human carotid plaque specimens, in vivo molecular imaging studies are warranted to test 68Ga-CM246 PET as a tool to stratify risk in atherosclerotic patients.
BACKGROUND AND PURPOSE: High-risk atherosclerosis is an underlying cause of cardiovascular events, yet identifying the specific patient population at immediate risk is still challenging. Here, we used a rabbit model of atherosclerotic plaque rupture and human carotid endarterectomy specimens to describe the potential of molecular fibrin imaging as a tool to identify thrombotic plaques. METHODS: Atherosclerotic plaques in rabbits were induced using a high-cholesterol diet and aortic balloon injury (N=13). Pharmacological triggering was used in a group of rabbits (n=9) to induce plaque disruption. Animals were grouped into thrombotic and nonthrombotic plaque groups based on gross pathology (gold standard). All animals were injected with a novel fibrin-specific probe 68Ga-CM246 followed by positron emission tomography (PET)/magnetic resonance imaging 90 minutes later. 68Ga-CM246 was quantified on the PET images using tissue-to-background (back muscle) ratios and standardized uptake value. RESULTS: Both tissue-to-background (back muscle) ratios and standardized uptake value were significantly higher in the thrombotic versus nonthrombotic group (P<0.05). Ex vivo PET and autoradiography of the abdominal aorta correlated positively with in vivo PET measurements. Plaque disruption identified by 68Ga-CM246 PET agreed with gross pathology assessment (85%). In ex vivo surgical specimens obtained from patients undergoing elective carotid endarterectomy (N=12), 68Ga-CM246 showed significantly higher binding to carotid plaques compared to a D-cysteine nonbinding control probe. CONCLUSIONS: We demonstrated that molecular fibrin PET imaging using 68Ga-CM246 could be a useful tool to diagnose experimental and clinical atherothrombosis. Based on our initial results using human carotid plaque specimens, in vivo molecular imaging studies are warranted to test 68Ga-CM246 PET as a tool to stratify risk in atherosclerotic patients.
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