Molecular imaging with optical coherence tomography using ligand-conjugated microparticles that detect activated endothelial cells: Rational design through target quantification

Andrew Jefferson, Rohan S. Wijesurendra, Martina A. McAteer, Janet E. Digby, Gillian Douglas, Thomas Bannister, Francisco Perez-Balderas, Zsolt Bagi, Alistair C. Lindsay, Robin P. Choudhury

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objectives: Optical coherence tomography (OCT) is a high resolution imaging technique used to assess superficial atherosclerotic plaque morphology. Utility of OCT may be enhanced by contrast agents targeting molecular mediators of inflammation. Methods and results: Microparticles of iron oxide (MPIO; 1 and 4.5μm diameter) in suspension were visualized and accurately quantified using a clinical optical coherence tomography system. Bound to PECAM-1 on a plane of cultured endothelial cells under static conditions, 1μm MPIO were also readily detected by OCT. To design a molecular contrast probe that would bind activated endothelium under conditions of shear stress, we quantified the expression (basal vs. TNF-activated; moleculesμm -2) of VCAM-1 (not detected vs. 16±1); PECAM-1 (132±6 vs. 198±10) and E-selectin (not detected vs. 46±0.6) using quantitative flow cytometry. We then compared the retention of antibody-conjugated MPIO targeting each of these molecules plus a combined VCAM-1 and E-selectin (E+V) probe across a range of physiologically relevant shear stresses. E+V MPIO were consistently retained with highest efficiency (P<0.001) and at a density that provided conspicuous contrast effects on OCT pullback. Conclusion: Microparticles of iron oxide were detectable using a clinical OCT system. Assessment of binding under flow conditions recommended an approach that targeted both E-selectin and VCAM-1. Bound to HUVEC under conditions of flow, targeted 1 μm E + V MPIO were readily identified on OCT pullback. Molecular imaging with OCT may be feasible in vivo using antibody targeted MPIO.

Original languageEnglish (US)
Pages (from-to)579-587
Number of pages9
JournalAtherosclerosis
Volume219
Issue number2
DOIs
StatePublished - Dec 1 2011

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Molecular Imaging
Optical Coherence Tomography
Endothelial Cells
Ligands
E-Selectin
Vascular Cell Adhesion Molecule-1
CD31 Antigens
Molecular Probes
Inflammation Mediators
Antibodies
Atherosclerotic Plaques
Contrast Media
Endothelium
Cultured Cells
Suspensions
Flow Cytometry

Keywords

  • Inflammation
  • Microparticles
  • Molecular imaging
  • OCT

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Molecular imaging with optical coherence tomography using ligand-conjugated microparticles that detect activated endothelial cells : Rational design through target quantification. / Jefferson, Andrew; Wijesurendra, Rohan S.; McAteer, Martina A.; Digby, Janet E.; Douglas, Gillian; Bannister, Thomas; Perez-Balderas, Francisco; Bagi, Zsolt; Lindsay, Alistair C.; Choudhury, Robin P.

In: Atherosclerosis, Vol. 219, No. 2, 01.12.2011, p. 579-587.

Research output: Contribution to journalArticle

Jefferson, A, Wijesurendra, RS, McAteer, MA, Digby, JE, Douglas, G, Bannister, T, Perez-Balderas, F, Bagi, Z, Lindsay, AC & Choudhury, RP 2011, 'Molecular imaging with optical coherence tomography using ligand-conjugated microparticles that detect activated endothelial cells: Rational design through target quantification', Atherosclerosis, vol. 219, no. 2, pp. 579-587. https://doi.org/10.1016/j.atherosclerosis.2011.07.127
Jefferson, Andrew ; Wijesurendra, Rohan S. ; McAteer, Martina A. ; Digby, Janet E. ; Douglas, Gillian ; Bannister, Thomas ; Perez-Balderas, Francisco ; Bagi, Zsolt ; Lindsay, Alistair C. ; Choudhury, Robin P. / Molecular imaging with optical coherence tomography using ligand-conjugated microparticles that detect activated endothelial cells : Rational design through target quantification. In: Atherosclerosis. 2011 ; Vol. 219, No. 2. pp. 579-587.
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AU - Digby, Janet E.

AU - Douglas, Gillian

AU - Bannister, Thomas

AU - Perez-Balderas, Francisco

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AU - Lindsay, Alistair C.

AU - Choudhury, Robin P.

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