Targeted ultrasound contrast agents: In vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl lewisx

Gregory E.R. Weller, Flordeliza S. Villanueva, Eric M. Tom, William R. Wagner

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

An ultrasound-based molecular imaging technique capable of detecting endothelial cell markers of inflammation may allow early, non-invasive assessment of vascular disease. Clinical application of targeted, acoustically-active microbubbles requires optimization of microbubble- endothelial adhesion strength to maximize image signal-to-noise ratio, as well as the ability to discern the degree of inflammation along a continuum of dysfunction. Accordingly, we hypothesized that adhesion of intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles is dependent on the degree of endothelial inflammation, and that microbubbles multi-targeted to both ICAM-1 (via anti-ICAM-1 antibodies) and selectins (via sialyl Lewisx) demonstrate greater adhesion strength than microbubbles targeted to either inflammatory marker alone. In a radial flow chamber, microbubbles were perfused across endothelial cells activated with interleukin-1β to four different levels of inflammation, as assessed by quantitative ICAM-1 expression. ICAM-1-targeted microbubble adhesion strength increased with increasing degree of inflammation, with a relationship that was both positive and linear (r> 0.99). Microbubble adhesion strength was significantly higher for the multi-targeted microbubbles than either of the single-targeted microbubbles. These data thus demonstrate that multi-targeting of contrast microbubbles may offer improved adhesion characteristics, allowing for greater sensitivity to inflammation. Furthermore, the adhesion strength of targeted microbubbles is linearly dependent on the degree of inflammation, suggesting that targeted ultrasound imaging may offer differentiation between various degrees of endothelial dysfunction, and thus detect not only the presence, but also the severity of inflammatory disease processes.

Original languageEnglish (US)
Pages (from-to)780-788
Number of pages9
JournalBiotechnology and bioengineering
Volume92
Issue number6
DOIs
StatePublished - Dec 20 2005

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Microbubbles
Bond strength (materials)
Intercellular Adhesion Molecule-1
Contrast Media
Adhesion
Ultrasonics
Molecules
Endothelial cells
Inflammation
Molecular imaging
Imaging techniques
Selectins
Radial flow
Interleukin-1
Signal to noise ratio
In Vitro Techniques
Antibodies
Endothelial Cells
Molecular Imaging
Signal-To-Noise Ratio

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

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abstract = "An ultrasound-based molecular imaging technique capable of detecting endothelial cell markers of inflammation may allow early, non-invasive assessment of vascular disease. Clinical application of targeted, acoustically-active microbubbles requires optimization of microbubble- endothelial adhesion strength to maximize image signal-to-noise ratio, as well as the ability to discern the degree of inflammation along a continuum of dysfunction. Accordingly, we hypothesized that adhesion of intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles is dependent on the degree of endothelial inflammation, and that microbubbles multi-targeted to both ICAM-1 (via anti-ICAM-1 antibodies) and selectins (via sialyl Lewisx) demonstrate greater adhesion strength than microbubbles targeted to either inflammatory marker alone. In a radial flow chamber, microbubbles were perfused across endothelial cells activated with interleukin-1β to four different levels of inflammation, as assessed by quantitative ICAM-1 expression. ICAM-1-targeted microbubble adhesion strength increased with increasing degree of inflammation, with a relationship that was both positive and linear (r> 0.99). Microbubble adhesion strength was significantly higher for the multi-targeted microbubbles than either of the single-targeted microbubbles. These data thus demonstrate that multi-targeting of contrast microbubbles may offer improved adhesion characteristics, allowing for greater sensitivity to inflammation. Furthermore, the adhesion strength of targeted microbubbles is linearly dependent on the degree of inflammation, suggesting that targeted ultrasound imaging may offer differentiation between various degrees of endothelial dysfunction, and thus detect not only the presence, but also the severity of inflammatory disease processes.",
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Targeted ultrasound contrast agents : In vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl lewisx. / Weller, Gregory E.R.; Villanueva, Flordeliza S.; Tom, Eric M.; Wagner, William R.

In: Biotechnology and bioengineering, Vol. 92, No. 6, 20.12.2005, p. 780-788.

Research output: Contribution to journalArticle

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T2 - In vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl lewisx

AU - Weller, Gregory E.R.

AU - Villanueva, Flordeliza S.

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AU - Wagner, William R.

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