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Theranostics 2011; 1:18-27. doi:10.7150/thno/v01p0018 This volume Cite

Research Paper

Real-Time Video Imaging of Protease Expression In Vivo

Lei Zhu^1,2, Jin Xie¹, Magdalena Swierczewska^1,3, Fan Zhang¹, Qimeng Quan¹, Ying Ma¹, Xuexun Fang², Kwangmeyung Kim⁴, Seulki Lee^1,✉, Xiaoyuan Chen^1,✉

1. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, USA
2. Key Laboratory of Molecular Enzymology and Enzyme Engineering of Ministry Education, Jilin University, Changchun 130023, P.R. China
3. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA
4. Biomedical Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea

✉ Corresponding author: X.C. (Shawn.Chengov) or S.L. (Seulki.Leegov).

Abstract

We demonstrate the first true real-time in vivo video imaging of extracellular protease expression using an ultrafast-acting and extended-use activatable probe. This simple, one-step technique is capable of boosting fluorescent signals upon target protease cleavage as early as 30 minutes from injection in a small animal model and is able to sustain the strong fluorescent signal up to 24 hours. Using this method, we video imaged the expression and inhibition of matrix metalloproteinases (MMPs) in a tumor-bearing mouse model. The current platform can be universally applied to any target protease of interest with a known peptide substrate and is adaptable to a wide range of real-time imaging applications with high throughputs such as for in vivo drug screening, examinations of the therapeutic efficacy of drugs, and monitoring of disease onset and development in animal models.

Keywords: matrix metalloproteinases (MMPs), activatable probes, near-infrared fluorescence imaging, real-time in vivo video imaging, peptide substrate, PEGylation.

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