In vivo molecular target assessment of matrix metalloproteinase inhibition
Abstract
A number of different matrix metalloproteinase (MMP) inhibitors have been developed as cytostatic and anti-angiogenic agents and are currently in clinical testing. One major hurdle in assessing the efficacy of such drugs has been the inability to sense or image anti-proteinase activity directly and non-invasively in vivo. We show here that novel, biocompatible near-infrared fluorogenic MMP substrates can be used as activatable reporter probes to sense MMP activity in intact tumors in nude mice. Moreover, we show for the first time that the effect of MMP inhibition can be directly imaged using this approach within hours after initiation of treatment using the potent MMP inhibitor, prinomastat (AG3340). The developed probes, together with novel near-infrared fluorescence imaging technology will enable the detailed analysis of a number of proteinases critical for advancing the therapeutic use of clinical proteinase inhibitors.
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The MMPSense 680 probe allows in vivo imaging of key MMPs, including MMP-2 as well as MMP-3, -9, -7, -12, and -13.
“It allows in vivo imaging of key MMPs, including MMP-2 as well as MMP-3, -9, -7, -12, and -13 (4, 32).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [4]
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“Protease-activated probes may provide increased tumor to normal contrast as they are designed to be optically inactive until cleaved by proteases that are highly expressed in tumors, like cathepsin proteases and matrix metalloproteases (MMPs) (13, 22-24).”
BackgroundMolecular imaging of the tumor microenvironment
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- Authors
- Bremer, C., Tung, C.-H., & Weissleder, R.
- Affiliations
- Harvard University (US)
- Corresponding author
- Tung, Ching-Hsuan
- Weissleder, Ralph
- Venue
- Nature Medicine
- Published
- 2001-06
- Volume
- 7
- Issue
- 6
- Pages
- 743-748
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1572736799
- Cited by
- 726
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 19 · 2020: 13 · 2019: 25 · 2018: 24 · 2017: 26 · 2016: 23 · 2015: 22 · 2014: 35 · 2013: 30 · 2012: 43
- FWCI
- 16.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA088365)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Keywords
- matrix metalloproteinase inhibition, prinomastat, angiogenesis inhibitors, tumor imaging, nude mice, protease inhibitors, drug efficacy evaluation
- MeSH terms
- Animals, Antineoplastic Agents, Cell Line, Diagnostic Imaging, Fibrosarcoma, Fluorescence, Fluorescent Dyes, Humans, Mammary Neoplasms, Experimental, Mice, Nude, Neoplasms, Experimental, Organic Chemicals, Peptides, Protease Inhibitors, Spectroscopy, Near-Infrared, Matrix Metalloproteinase 2, Matrix Metalloproteinases, Mice, Matrix Metalloproteinase Inhibitors
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