Macrophage-Specific Lipid-Based Nanoparticles Improve Cardiac Magnetic Resonance Detection and Characterization of Human Atherosclerosis

JACC-CARDIOVASCULAR IMAGING

卷:2

Article

Lipinski, Michael J.^1,2,3,4,5  Frias, Juan C.^1,2,6  Amirbekian, Vardan^1,2,7  Briley-Saebo, Karen C.^1,2  Mani, Venkatesh^1,2  Samber, Daniel^1,2  Abbate, Antonio⁴  Aguinaldo, Juan Gilberto S.^1,2  Massey, Davis^1,8  Fuster, Valentin³  Vetrovec, George W.⁴  Fayad, Zahi A.^1,2,3 

[1] Mt Sinai Med Ctr, Translat & Mol Imaging Inst, New York, NY 10029 USA

[2] Mt Sinai Med Ctr, Imaging Sci Labs, Dept Radiol, New York, NY 10029 USA

[3] Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovasc Inst, Marie Josee & Henry R Kravis Cardiovasc Hlth Ct, Dept Internal Med,Div Cardiol, New York, NY 10029 USA

[4] Virginia Commonwealth Univ, VCU Pauley Heart Ctr, Richmond, VA USA

[5] Univ Virginia Hlth Syst, Dept Internal Med, Charlottesville, VA USA

[6] Univ Valencia, Inst Ciencia Mol, Valencia, Spain

[7] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA

[8] Virginia Commonwealth Univ Hlth Syst, Dept Pathol, Richmond, VA USA

关键词: atherosclerosis;    CD36;    macrophage;    magnetic resonance imaging;    nanoparticles;   

DOI  :  10.1016/j.jcmg.2008.08.009

来源: Elsevier

【 摘 要 】

OBJECTIVES We sought to determine whether gadolinium (Gd)-containing lipid-based nanoparticles (NPs) targeting the macrophage scavenger receptor-B (CD36) improve cardiac magnetic resonance (CMR) detection and characterization of human atherosclerosis. BACKGROUND Gd-containing lipid-based NPs targeting macrophages have improved MR detection of murine atherosclerosis. METHODS Gadolinium-containing untargeted NPs, anti-CD36 NPs, and nonspecific Fc-NPs were created. Macrophages were incubated with fluorescent targeted and nontargeted NPs to determine uptake via confocal microscopy and inductively coupled plasma mass spectroscopy (ICP-MS) quantified Gd uptake. Human aortic specimens were harvested at autopsy. With a 1.5-T scanner, T1, T2, and PDW 3-dimensional scans were performed along with post-contrast scans after 24 h incubation. The T1 and cluster analyses were performed and compared with immunohistopathology. RESULTS The NPs had a mean diameter of 125 nm and 14,900 Gd-ions, and relaxivity was 37 mmol/l(-1)s(-1) at 1.5-T and 37 degrees C. Confocal microscopy and ICP-MS demonstrated significant in vitro macrophage uptake of targeted NPs, whereas non-targeted NPs had minimal uptake. On T1 imaging, targeted NPs increased contrast-to-noise ratio (CNR) by 52.5%, which was significantly greater than Fc-NPs (CNR increased 17.2%) and nontargeted NPs (CNR increased 18.7%) (p = 0.001). Confocal fluorescent microscopy showed that NPs target resident macrophages, whereas the untargeted NPs and Fc-NPs are found diffusely throughout the plaque. Targeted NPs had a greater signal intensity increase in the fibrous cap compared with non-targeted NPs. CONCLUSIONS Macrophage-specific (CD36) NPs bind human macrophages and improve CMR detection and characterization of human aortic atherosclerosis. Thus, macrophage-specific NPs could help identify high-risk human plaque before the development of an atherothrombotic event. (J Am Coll Cardiol Img 2009; 2: 637-47) (C) 2009 by the American College of Cardiology Foundation

【 授权许可】

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