Abstract WP526: Molecular Imaging of Carotid Plaques Using a Fibrin-Binding PET Probe

Abstract

Objectives: We aim to develop molecular fibrin imaging as a tool to stratify high risk atherosclerotic carotid plaques. Here, we describe our results with a fibrin-specific probe [ 68 Ga]CM-246 in two different experimental settings: ex vivo imaging of carotid endarterectomy specimens and in vivo / ex vivo imaging of atherosclerotic plaque rupture in rabbits. Methods: We incubated discarded endarterectomy specimens (n=11) from asymptomatic patients with [ 68 Ga] CM-246 or a scrambled peptide control probe and measured uptake by autoradiography and a tissue binding assay. In a rabbit plaque rupture model of high cholesterol diet followed by abdominal aorta balloon injury (n=13) and subsequent pharmacological plaque rupture, in vivo and ex vivo PET-MR with [ 68 Ga]CM-246 was performed. Tissues were processed for autoradiography and histology to verify presence of fibrin and plaque rupture. Results: Autoradiography (A-B) and tissue binding assays (C) with [ 68 Ga]CM-246 with human carotid plaques show increased tissue binding compared with non-specific control probe. Carstair’s staining (D) verified the presence of fibrin in the specimens (red stained areas). Rabbits with plaque rupture had an increase in [ 68 Ga]CM-246 signal in the abdominal aorta compared with the control group. At 105-120 min post probe injection, there was a clear PET uptake on the aorta in plaque rupture rabbit (E) compared with control rabbit (F). MR images were used to differentiate abdominal aorta (green arrows) and the inferior vena cava (blue arrows). T2-dark blood images confirmed the plaques in rupture (G) and control rabbits (H). ToF images were used to visualize aortic lumen in plaque rupture (I) and control rabbits (J). Ex-vivo PET imaging, autoradiography, and histology confirmed in vivo results. Conclusions: We demonstrated that [ 68 Ga]CM-246 detects high-risk plaque in human and rabbits and can be a useful tool for the stratification of atherosclerotic plaques in patients.