Journal
MOLECULAR PHARMACEUTICS
Volume 11, Issue 11, Pages 4208-4217Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp500443x
Keywords
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Funding
- National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health
- National Science Foundation of China (NSFC) [81301256]
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Matrix metalloproteases (MMPs) have been found to be highly expressed in a variety of malignant tumor tissues. Noninvasive visualization of MMP activity may play an important role in the diagnosis of MMP associated diseases. Here we report the design and synthesis of a set of fluorine-19 dendron-based magnetic resonance imaging (MRI) probes for real-time imaging of MMP-2 activity. The probes have the following features: (a) symmetrical fluorine atoms; (b) the number of fluorine atoms can be increased through facile chemical modification; (c) readily accessible peptide sequence as the MMP-2 substrate; (d) activatable (19)F signal (off/on mode) via paramagnetic metal ion incorporation. Following optimization for water solubility, one of the probes was selected to evaluate MMP-2 activity by (19)F magnetic resonance spectroscopy (MRS). Our results showed that the fluorine signal increased by 8.5-fold in the presence of MMP-2. The specific cleavage site was verified by mass spectrometry. The selected probe was further applied to detect secreted MMP-2 activity of living SCC7 squamous cell carcinoma cells. The fluorine signal was increased by 4.8-fold by MRS analysis after 24 h incubation with SCC7 cells. This type of fluorine probe can be applied to evaluate other enzyme activities by simply tuning the substrate structures. This symmetrical fluorine dendron-based probe design extends the scope of the existing (19)F MRI agents and provides a simple but robust method for real-time (19)F MRI application.
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