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Localization to atherosclerotic plaque and biodistribution of biochemically derivatized superparamagnetic iron oxide nanoparticles (SPIONs) contrast particles for magnetic resonance imaging (MRI)

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An ERRATUM to this article was published on 19 December 2007

Abstract

Annexin V recognizes apoptotic cells by specific molecular interaction with phosphatidyl serine, a lipid that is normally sequestered in the inner leaflet of the cell membrane, but is translocated to the outer leaflet in apoptotic cells, such as foam cells of atherosclerotic plaque. Annexin V could potentially deliver carried materials (such as superparamagnetic contrast agents for magnetic resonance imaging) to sites containing apoptotic cells, such as high grade atherosclerotic lesions, so we administered biochemically-derivatized (annexin V) superparmagnetic iron oxide particles (SPIONs) parenterally to two related rabbit models of human atherosclerosis. We observe development of negative magnetic resonance imaging (MRI) contrast in atheromatous lesions and but not in healthy artery. Vascular targeting by annexin V SPIONs is atheroma-specific (i.e., does not occur in healthy control rabbits) and requires active annexin V decorating the SPION surface. Targeted SPIONs produce negative contrast at doses that are 2,000-fold lower than reported for non-specific atheroma uptake of untargeted superparamagnetic nanoparticles in plaque in the same animal model. Occlusive and mural plaques are differentiable. While most of the dose accumulates in liver, spleen, kidneys and bladder, annexin V SPIONs also partition rapidly and deeply into early apoptotic foamy macrophages in plaque. Contrast in plaque decays within 2 months, allowing MRI images to be replicated with a subsequent, identical dose of annexin V SPIONs. Thus, biologically targeted superparamagnetic contrast agents can contribute to non-invasive evaluation of cardiovascular lesions by simultaneously extracting morphological and biochemical data from them.

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Acknowledgments

The authors acknowledge George Hinkle, Charles Hitchcock, Nathan Hall, Noe Tirado-Muniz, Krista LaPerle and Donna Kusewitt for their technical support and advice. This work supported was by BRTT02-0001, a grant from the Biomedical Research and Technology Transfer Commission of Ohio and National Science Foundation Grant No. 0221678.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Ohio State University, 1080 Carmack Road, Columbus, OH, 43210, USA

    Bryan R. Smith, John Shapiro & Nicanor I. Moldovan

  2. Department of Radiology, Ohio State University, 630 Means Hall, 1654 Upham Drive, Columbus, OH, 43210, USA

    Johannes Heverhagen, Michael Knopp & Petra Schmalbrock

  3. Institute for Experimental Animals, Kobe University Graduate School of Medicine, Kobe, Japan

    Masashi Shiomi

  4. Brown Institute of Molecular Medicine, Department of Biomedical Engineering, The University of Texas Health Science Center, 1825 Pressler, Suite 537D, Houston, TX, 77031, USA

    Mauro Ferrari

  5. Departments of Biomedical Engineering, Chemical and Biomolecular Engineering, Cellular and Molecular Biochemistry, Davis Heart and Lung Research Institute, Ohio State University, 473 W. 12th Ave., Columbus, OH, 43210, USA

    Stephen C. Lee

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  1. Bryan R. Smith
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  2. Johannes Heverhagen
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Correspondence to Stephen C. Lee.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10544-007-9136-5

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Smith, B.R., Heverhagen, J., Knopp, M. et al. Localization to atherosclerotic plaque and biodistribution of biochemically derivatized superparamagnetic iron oxide nanoparticles (SPIONs) contrast particles for magnetic resonance imaging (MRI). Biomed Microdevices 9, 719–727 (2007). https://doi.org/10.1007/s10544-007-9081-3

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