Biomedical Microdevices

, Volume 9, Issue 5, pp 719–727 | Cite as

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

  • Bryan R. Smith
  • Johannes Heverhagen
  • Michael Knopp
  • Petra Schmalbrock
  • John Shapiro
  • Masashi Shiomi
  • Nicanor I. Moldovan
  • Mauro Ferrari
  • Stephen C. Lee


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.


Vascular imaging Molecular imaging Targeted contrast Apoptosis Annexin V Superparamagnetic 



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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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Bryan R. Smith
    • 1
  • Johannes Heverhagen
    • 2
  • Michael Knopp
    • 2
  • Petra Schmalbrock
    • 2
  • John Shapiro
    • 1
  • Masashi Shiomi
    • 3
  • Nicanor I. Moldovan
    • 1
  • Mauro Ferrari
    • 4
  • Stephen C. Lee
    • 5
  1. 1.Department of Biomedical EngineeringOhio State UniversityColumbusUSA
  2. 2.Department of RadiologyOhio State UniversityColumbusUSA
  3. 3.Institute for Experimental AnimalsKobe University Graduate School of MedicineKobeJapan
  4. 4.Brown Institute of Molecular Medicine, Department of Biomedical EngineeringThe University of Texas Health Science CenterHoustonUSA
  5. 5.Departments of Biomedical Engineering, Chemical and Biomolecular Engineering, Cellular and Molecular Biochemistry, Davis Heart and Lung Research InstituteOhio State UniversityColumbusUSA

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