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Factors affecting the endothelial retention of targeted microbubbles: influence of microbubble shell design and cell surface projection of the endothelial target molecule

Khanicheh, E. and Mitterhuber, M. and Kinslechner, K. and Xu, L. and Lindner, J. R. and Kaufmann, B. A.. (2012) Factors affecting the endothelial retention of targeted microbubbles: influence of microbubble shell design and cell surface projection of the endothelial target molecule. Journal of the American Society of Echocardiography, Vol. 25, H. 4. pp. 460-466.

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Official URL: http://edoc.unibas.ch/dok/A6338425

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Abstract

BACKGROUND: In biologic systems, the arrest of circulating cells is mediated by adhesion molecules projecting their active binding domain above the cell surface to enhance bond formation and tether strength. Similarly, molecular spacers are used for ligands on particle-based molecular imaging agents. The aim of this study was to evaluate the influence of tether length for targeting ligands on ultrasound molecular imaging agents. METHODS: Microbubbles bearing biotin at the end of variable-length polyethylene glycol spacer arms (MB(2000) and MB(3400)) were prepared. To assess in vivo attachment efficiency to endothelial counterligands that vary in their distance from the endothelial cell surface, contrast-enhanced ultrasound (CEU) molecular imaging of tumor necrosis factor-alpha-induced P-selectin (long distance) or intercellular adhesion molecule-2 (short distance) was performed with each agent in murine hind limbs. To assess the influence of the glycocalyx on microbubble attachment, CEU molecular imaging of intercellular adhesion molecule-2 was performed after degradation of the glycocalyx. RESULTS: CEU molecular imaging targeted to P-selectin showed signal enhancement above control agent for MB(2000) and MB(3400), the degree of which was significantly higher for MB(3400) compared with MB(2000). CEU molecular imaging targeted to intercellular adhesion molecule-2 showed low overall signal for all agents and signal enhancement above control for MB(3400) only. Glycocalyx degradation increased signal for MB(3400) and MB(2000). CONCLUSIONS: Microbubble targeting to endothelial ligands is influenced by (1) the tether length of the ligand, (2) the degree to which the endothelial target is projected from the cell surface, and (3) the status of the glycocalyx. These considerations are important for designing targeted imaging probes and understanding potential obstacles to molecular imaging.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cardiovascular Molecular Imaging (Kaufmann)
UniBasel Contributors:Kaufmann, Beat
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Mosby/Elsevier
ISSN:0894-7317
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:08 May 2015 08:45

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