Fluorescently labeled microbubbles for facilitating translational molecular ultrasound studies

P. Koczera, Z. Wu, S. Fokong, B. Theek, L. Appold, S. Jorge, D. Möckel, Z. Liu, A. Curaj, Gerrit Storm, M. van Zandvoort, F. Kiessling, Twan Gerardus Gertudis Maria Lammers

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)

Abstract

Abstract Microbubbles (MB) are routinely used as contrast agents for functional and molecular ultrasound (US) imaging. For molecular US imaging, MB are functionalized with antibodies or peptides, in order to visualize receptor expression by angiogenic or inflamed endothelium. In general, initial in vitro binding studies with targeted MB are performed using phase contrast microscopy. Difficulties in the identification of MB in standard phase contrast microscopy, however, generally result in high variability, high observer dependency, and low reproducibility. To overcome these shortcomings, we here describe a simple post-loading strategy for labeling polymer-based MB with fluorophores, and we show that the use of rhodamine-loaded MB in combination with fluorescence microscopy substantially reduces the variability and the observer dependency of in vitro binding studies. In addition, we demonstrate that rhodamine-loaded MB can also be used for in vivo and ex vivo experimental setups, e.g., for analyzing MB binding to inflamed carotids using two-photon laser scanning microscopy, and for validating the binding of VEGFR2-targeted MB to tumor endothelium. These findings demonstrate that fluorescently labeled MB substantially facilitate translational molecular US studies, and they suggest that a similar synthetic strategy can be exploited for preparing drug-loaded MB, to enable image-guided, targeted, and triggered drug delivery to tumors and to sites of inflammation.
Original languageEnglish
Pages (from-to)56-64
JournalDrug delivery and translational research
Volume2
Issue number1
DOIs
Publication statusPublished - 2012

Keywords

  • IR-83083
  • METIS-292676

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