MPI/FLI/CTA multi-modality imaging of atherosclerotic plaque with plexind1-targeted nanoparticles

Abstract

Abstract M1 macrophage is one of important components which contribute to the progression of atherosclerotic plaques.[1]Previous research of our team showed that plexind1 was expressed more in atherosclerotic plaques at vascular bifurcation than those at straight site and co-localized with M1 macrophages. This study aims to develop a novel multimodal imaging platform by designing a nanoprobe targeting plexind1 to detect and monitor bifurcation lesion and provide detecting method for animal research. Methods A novel multimodal imaging agent,A12-Fe3O4-Cy7, was constructed by coupling superparamagnetic iron oxide nanoparticle (SPIONs) with cyanine 7 N-hydroxysuccin imide ester（Cy7）and nanobody A12 which could target plexind1 specifically. The physical and biological properties were evaluated. To assess the A12-Fe3O4-Cy7 recognition and monitoring for plaque,high-fat-fed 10-week and 20-week Apoe-/- atherosclerosis mouse models were imaged using MPI and FLI,and both 3D images were fused with CTA. HE,Prussian blue and plexind1 immunohistochemical staining were performed on mouse carotid tissue sections. Results The A12-Fe3O4-Cy7 was of favorable stability, biocompatibility（concentration< 200ug/ml) and targeting effect.It could detect, locate, and monitor atherosclerotic plaques at bifurcation of carotid artery in ApoE-/- mice accurately and sensitively, showing significantly higher MPI and FLI signals both in vivo and ex vivo compared with both themselves before nanoprobe injection and two control groups(n=3,p<0.05). FLI is more sensitive than MPI to detect high-fat-fed 10-week mouse plaques.The results were confirmed histologically. Conclusion A12-Fe3O4-Cy7 might serve as a method to detect plaques at the bifurcation by targeting plexind1 in vivo. Limitations MPI is tested only in mouse models presently and it requires combination with CT to provide anatomical information. Besides，there was no intervention on plexind1,so the mechanism of plexind1 in bifurcation plaque occurrence and progression is not illustrated clearly,which is worth exploring in the future.In vitro and vivo assessmentIn vivo and ex vivo imaging