Abstract 324: Molecular Imaging of High Risk Atherosclerotic Plaque Using Fibrin-Binding PET Probe

Abstract

Objectives: There is a need for better stratification of atherosclerotic patients to identify individuals at high risk for a cardiovascular event. Two key hallmarks of plaque at high risk for rupture are intraplaque hemorrhage and evidence of prior rupture. The protein fibrin is strongly associated with both hemorrhage and rupture but it is not present in earlier stages of plaque development, suggesting that fibrin imaging would be sensitive for high risk plaque versus stable/early disease. Here, we describe imaging properties of a fibrin-specific PET probe for atherosclerotic plaque rupture in rabbits. Methods: Rabbits were fed with high cholesterol diet (HCD) for 8 weeks followed by 2 weeks of normal diet. Two weeks after the initiation of HCD, endothelial denudation of abdominal aorta was performed using balloon catheter. At 10 weeks, rabbits were randomly divided into plaque rupture (n=8; triggered by Russell’s viper venom and histamine) and control group (n=4), injected with fibrin-binding probe [ 68 Ga]CM-246, and scanned on a PET/MRI. Then, vessels of interest were removed for ex-vivo PET, autoradiography, and histology. Results: Rabbits with plaque rupture had >2-fold increase in [ 68 Ga]CM-246 signal in the abdominal aorta compared with the control group (A). At 105-120 min post probe injection, there was a clear PET uptake on the aorta in plaque rupture rabbit (B) compared with control rabbit (C). MR images were used to differentiate abdominal aorta (green arrows) and the inferior vena cava (blue arrows). T2-dark blood images confirmed the atherosclerotic plaques in plaque rupture (D) and control rabbits (E). ToF images were used to visualize aortic lumen in plaque rupture (F) and control rabbits (G). Ex vivo PET imaging (H) and autoradiography confirmed in vivo results. Conclusions: We demonstrated that [ 68 Ga]CM-246 detects atherosclerotic plaque rupture in a rabbit model and can be a useful tool for the diagnosis of high-risk atherosclerotic plaque in patients.