Functionalization of gadolinium metallofullerenes for detecting atherosclerotic plaque lesions by cardiovascular magnetic resonance

Journal of Cardiovascular Magnetic Resonance

Research

Jijin Yang¹  John Olson²  Kerry Link²  Christopher L Kepley³  Marinella G Sandros³  Stephen Vance³  Zhiguo Zhou⁴  Anthony Dellinger⁵ 

[1] Carl Zeiss Microscopy, LLC, One Zeiss Drive, 10594, Thornwood, NY, USA;Center for Biomolecular Imaging, Wake Forest University, 1 Medical Center Blvd, 27157, Winston Salem, NC, USA;Joint School of Nanoscience and Nanoengineering, 2907 E Lee St, 27401, Greensboro, NC, USA;Luna Innovations Incorporated, Luna nanoWorks Division, 521 Bridge St, 24541, Danville, VA, USA;Luna Innovations Incorporated, Luna nanoWorks Division, 521 Bridge St, 24541, Danville, VA, USA;Joint School of Nanoscience and Nanoengineering, 2907 E Lee St, 27401, Greensboro, NC, USA;

关键词: Atherosclerosis;    Magnetic resonance imaging;    Metallofullerenes;    Contrast agent;    Macrophage;    CD36;   

DOI  :  10.1186/1532-429X-15-7

 received in 2011-08-23, accepted in 2012-12-17,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe hallmark of atherosclerosis is the accumulation of plaque in vessel walls. This process is initiated when monocytic cells differentiate into macrophage foam cells under conditions with high levels of atherogenic lipoproteins. Vulnerable plaque can dislodge, enter the blood stream, and result in acute myocardial infarction and stroke. Imaging techniques such as cardiovascular magnetic resonance (CMR) provides one strategy to identify patients with plaque accumulation.MethodsWe synthesized an atherosclerotic-targeting contrast agent (ATCA) in which gadolinium (Gd)-containing endohedrals were functionalized and formulated into liposomes with CD36 ligands intercalated into the lipid bilayer. In vitro assays were used to assess the specificity of the ATCA for foam cells. The ability of ATCA to detect atherosclerotic plaque lesions in vivo was assessed using CMR.ResultsThe ATCA was able to detect scavenger receptor (CD36)-expressing foam cells in vitro and were specifically internalized via the CD36 receptor as determined by focused ion beam/scanning electron microscopy (FIB-SEM) and Western blotting analysis of CD36 receptor-specific signaling pathways. The ATCA exhibited time-dependent accumulation in atherosclerotic plaque lesions of ApoE −/− mice as determined using CMR. No ATCA accumulation was observed in vessels of wild type (C57/b6) controls. Non-targeted control compounds, without the plaque-targeting moieties, were not taken up by foam cells in vitro and did not bind plaque in vivo. Importantly, the ATCA injection was well tolerated, did not demonstrate toxicity in vitro or in vivo, and no accumulation was observed in the major organs.ConclusionsThe ATCA is specifically internalized by CD36 receptors on atherosclerotic plaque providing enhanced visualization of lesions under physiological conditions. These ATCA may provide new tools for physicians to non-invasively detect atherosclerotic disease.

【 授权许可】

Unknown   
© Dellinger et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.