Fluorescently labeled microbubbles for facilitatin

Authors: Patrick Koczera Zhuojun Wu Stanley Fokong Benjamin Theek Lia Appold Samuel Jorge Diana Möckel Zhe Liu Adelina Curaj Gert Storm Marc van Zandvoort Fabian Kiessling Twan Lammers

Publish Date: 2012/01/20

Volume: 2, Issue: 1, Pages: 56-64

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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 postloading strategy for labeling polymerbased MB with fluorophores and we show that the use of rhodamineloaded MB in combination with fluorescence microscopy substantially reduces the variability and the observer dependency of in vitro binding studies In addition we demonstrate that rhodamineloaded MB can also be used for in vivo and ex vivo experimental setups eg for analyzing MB binding to inflamed carotids using twophoton laser scanning microscopy and for validating the binding of VEGFR2targeted 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 drugloaded MB to enable imageguided targeted and triggered drug delivery to tumors and to sites of inflammation

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