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Updated: Jun 14, 2026
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
Radiofluorinated pyrimidine-2,4,6-triones as molecular probes for noninvasive MMP-targeted imaging
Hans-Jörg Breyholz1, Stefan Wagner, Andreas Faust
1Department of Nuclear Medicine, University of Münster, Germany. breyholz@uni-muenster.de <breyholz@uni-muenster.de>
Abstract:
Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent endopeptidases. Representing a subfamily of the metzincin superfamily, MMPs are involved in the proteolytic degradation of components of the extracellular matrix. Unregulated MMP expression, MMP dysregulation and locally increased MMP activity are common features of various diseases, such as cancer, atherosclerosis, stroke, arthritis, and others. Therefore, activated MMPs are suitable biological targets for the specific visualization of such pathologies, in particular by using radiolabeled MMP inhibitors (MMPIs). The aim of this work was to develop a radiofluorinated molecular probe for noninvasive in vivo imaging for the detection of up-regulated levels of activated MMPs in the living organism. Fluorinated MMPIs (26, 31 and 38) based on the pyrimidine-2,4,6-trione lead structure RO 28-2653 (1) were synthesized, and their MMP inhibition potency was evaluated in vitro. The radiosynthesis and the in vivo biodistribution of the first (18)F-labeled prototype, MMP-targeted tracer [(18)F]26, suitable for molecular imaging by means of positron emission tomography (PET) were realized.
Insights
Researchers developed a novel radiofluorinated molecular probe for positron emission tomography (PET) imaging. This probe targets matrix metalloproteinases (MMPs), aiding in the noninvasive detection of diseases like cancer and arthritis.
Area of Science:
- Biochemistry
- Molecular Biology
- Radiochemistry
Background:
- Matrix metalloproteinases (MMPs) are enzymes crucial for extracellular matrix remodeling.
- Dysregulated MMP activity is implicated in various pathologies, including cancer, atherosclerosis, and arthritis.
- Targeting activated MMPs offers a strategy for disease visualization.
Purpose of the Study:
- To develop a novel radiofluorinated molecular probe for in vivo imaging of activated MMPs.
- To synthesize and evaluate fluorinated MMP inhibitors (MMPIs) for their potency.
- To enable noninvasive detection of MMP-related diseases using positron emission tomography (PET).
Main Methods:
- Synthesis of fluorinated MMPIs based on the pyrimidine-2,4,6-trione scaffold.
- In vitro evaluation of MMP inhibition potency.
- Radiosynthesis and in vivo biodistribution studies of the (18)F-labeled tracer [(18)F]26.
Main Results:
- Several fluorinated MMPIs were synthesized and their inhibitory potential assessed.
- The first (18)F-labeled MMP-targeted tracer, [(18)F]26, was successfully synthesized.
- Initial biodistribution studies demonstrated the feasibility of [(18)F]26 for in vivo imaging.
Conclusions:
- A novel (18)F-labeled MMPI, [(18)F]26, was developed as a potential PET imaging agent.
- This tracer shows promise for noninvasive visualization of activated MMPs in disease states.
- Further studies are warranted to validate its clinical utility for diagnosing MMP-related pathologies.
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