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Targeted Microbubbles: Ultrasound Contrast Agents for Molecular Imaging

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Nanoparticles in Biomedical Imaging

Part of the book series: Fundamental Biomedical Technologies ((FBMT,volume 102))

Abstract

Targeted ultrasound contrast microbubble materials are designed as hollow micron-size spheres with a biocompatible shell stabilizer. Excellent detection sensitivity of these particles (down to individual particles of a picogram mass) is achieved routinely with clinical ultrasound. To improve stability and in vivo circulation time, poorly soluble perfluorinated gases can be used as the particle core. Microbubble shell (from several to several hundred nanometers thick) can be made of protein, polymer, lipid, surfactant, or combinations of these. Targeting ligands (antibodies, peptides and mimetics, carbohydrates and combinations) can be attached to the shell, either directly or via a protein/polymer spacer arm. To improve targeting in fast flow conditions that are characterized by high wall shear stress, microbubbles can be outfitted with surface folds/microvilli. Alternatively, bio-inspired fastbinding ligands, such as peptides from P-selectin Glycoprotein Ligand-1 or sialyl Lewis carbohydrates can be applied.

Selective targeting of the microbubbles to the vascular markers of diseases was successful in multiple animal model studies. Selectins, integrins, or addressins on vascular endothelium surface that are upregulated in response to inflammation or ischemia-reperfusion injury have been targeted successfully, ultrasound contrast enhancement of target tissues achieved. Angiogenic endothelium in the tumor vasculature has been imaged by targeting microbubbles to αvβ3 and similar molecules. Overall, the convenience, low cost, and real-time capabilities of ultrasound imaging, combined with molecular imaging capabilities of targeted microbubble contrast agents, may offer significant improvement in patient diagnostics and treatment progress monitoring.

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Authors
  1. Alexander L. Klibanov
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Editors and Affiliations

  1. Department of Radiology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, 21205

    Jeff W.M. Bulte

  2. Institute of Psychiatry King’s College London, Center for the Cellular Basis of Behaviour, 125 Coldharbour Lane, London SE5 9NU, United Kingdom

    Michel M.J. Modo

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Klibanov, A.L. (2008). Targeted Microbubbles: Ultrasound Contrast Agents for Molecular Imaging. In: Bulte, J.W., Modo, M.M. (eds) Nanoparticles in Biomedical Imaging. Fundamental Biomedical Technologies, vol 102. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72027-2_16

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