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

Research output: Contribution to journalArticle

79 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)719-727
Number of pages9
JournalBiomedical Microdevices
Volume9
Issue number5
DOIs
StatePublished - Oct 2007
Externally publishedYes

Keywords

  • Annexin V
  • Apoptosis
  • Molecular imaging
  • Superparamagnetic
  • Targeted contrast
  • Vascular imaging

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Genetics
  • Neuroscience(all)
  • Bioengineering
  • Biomedical Engineering

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