Magnetic Resonance Imaging of Atherosclerosis Using CD81-Targeted Microparticles of Iron Oxide in Mice.

Fei Yan,Lisi Xie,Bensheng Qiu,Xin Liu,Hairong Zheng,Xiang Li,Dongliang Zhou,Junru Wu,Guoxi Xie,Xiang Nan,Hongmei Liu,Wei Yang

doi:10.1155/2015/758616

Abstract

The goal of this study is to investigate the feasibility of using CD81- (Cluster of Differentiation 81 protein-) targeted microparticles of iron oxide (CD81-MPIO) for magnetic resonance imaging (MRI) of the murine atherosclerosis. CD81-MPIO and IgG- (Immunoglobulin G-) MPIO were prepared by covalently conjugating, respectively, with anti-CD81 monoclonal and IgG antibodies to the surface of the tosyl activated MPIO. The relevant binding capability of the MPIO was examined by incubating them with murine bEnd.3 cells stimulated with phenazine methosulfate (PMS) and its effect in shortening T2 relaxation time was also examined. MRI in apolipoprotein E-deficient mice was studied in vivo. Our results show that CD81-MPIO, but not IgG-MPIO, can bind to the PMS-stimulated bEnd.3 cells. The T2 relaxation time was significantly shortened for stimulated bEnd.3 cells when compared with IgG-MPIO. In vivo MRI in apolipoprotein E-deficient mice showed highly conspicuous areas of low signal after CD81-MPIO injection. Quantitative analysis of the area of CD81-MPIO contrast effects showed 8.96- and 6.98-fold increase in comparison with IgG-MPIO or plain MPIO, respectively (P < 0.01). Histological assay confirmed the expression of CD81 and CD81-MPIO binding onto atherosclerotic lesions. In conclusion, CD81-MPIO allows molecular assessment of murine atherosclerotic lesions by magnetic resonance imaging.

Highlights

Coronary artery disease arising from atherosclerosis is a leading cause of death, responsible for about 30% of all deaths worldwide, with more than 80% cases occurring in developing countries compared to developed countries [1, 2]
To test whether antibodies can bind to Micron-sized particles of iron oxide (MPIO), the particles were incubated with FITC-labeled anti-CD81 antibodies
In order to examine whether CD81-MPIO were able to improve contrast effects of endothelial cells, stress-stimulated or non-stress-stimulated bEnd.3 cells were incubated with various concentrations of CD81-MPIO or IgG-MPIO and imaged by MR imaging system

Summary

Introduction

Coronary artery disease arising from atherosclerosis is a leading cause of death, responsible for about 30% of all deaths worldwide, with more than 80% cases occurring in developing countries compared to developed countries [1, 2]. Atherosclerosis occurs through a slowly progressing lesion formation and luminal narrowing of arteries whereby lipids, inflammatory cells, and extracellular matrix accumulation in the subendothelial space (intima) lead to plaque formation. The early identification and characterization of atherosclerotic lesions remain challenging. Magnetic resonance imaging (MRI) has demonstrated substantial potential in phenotyping vascular disease. Magnetic resonance molecular imaging presents opportunities to image directly the biological processes of vascular disease at the molecular and cellular levels [4, 5]. By targeting molecules differentially expressed in disease states, purposebuilt molecular imaging probes can contribute to the molecular understanding of a range of diseases and potentially offer a means of clinical diagnosis [6]

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