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Updated: Mar 10, 2026
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
Optical imaging of MMP-12 active form in inflammation and aneurysm
Mahmoud Razavian1,2, Thomas Bordenave3, Dimitris Georgiadis4
1Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT USA.
Abstract:
Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm. Here, we developed a novel family of fluorescent probes based on a selective MMP-12 inhibitor, RXP470.1 to target the active form of MMP-12. These probes were stable in complex media and retained the high affinity and selectivity of RXP470.1 for MMP-12. Amongst these, probe 3 containing a zwitterionic fluorophore, ZW800-1, combined a favorable affinity profile toward MMP-12 and faster blood clearance. In vivo binding of probe 3 was observed in murine models of sterile inflammation and carotid aneurysm. Binding specificity was demonstrated using a non-binding homolog. Co-immunostaining localized MMP-12 probe binding to MMP-12 positive areas and F4/80 positive macrophages in aneurysm. In conclusion, the active form of MMP-12 can be detected by optical imaging using RXP470.1-based probes. This is a valuable adjunct for pathophysiology research, drug development, and potentially clinical applications.
Insights
Novel fluorescent probes targeting active matrix metalloproteinase (MMP)-12 were developed. These probes enable molecular imaging of MMP-12, aiding aneurysm research and drug development.
Area of Science:
- Biomedical imaging
- Molecular biology
- Cardiovascular research
Background:
- Matrix metalloproteinase (MMP)-12 is crucial in aneurysm development.
- MMP-12 is activated proteolytically, and imaging its active form is key for understanding pathogenesis.
- Current imaging methods for active MMP-12 are limited.
Purpose of the Study:
- To develop novel fluorescent probes for molecular imaging of active MMP-12.
- To evaluate the probes' affinity, selectivity, and stability.
- To assess the probes' efficacy in vivo using murine models.
Main Methods:
- Development of fluorescent probes based on the selective MMP-12 inhibitor RXP470.1.
- In vitro stability and affinity testing in complex media.
- In vivo optical imaging in murine models of sterile inflammation and carotid aneurysm.
- Specificity validation using a non-binding homolog and co-immunostaining.
Main Results:
- Novel RXP470.1-based fluorescent probes targeting active MMP-12 were successfully developed.
- Probe 3, featuring ZW800-1, showed high affinity, selectivity, and faster blood clearance.
- In vivo imaging demonstrated probe 3 binding in murine aneurysm models, localized to MMP-12 positive macrophages.
- Specificity was confirmed, indicating reliable detection of active MMP-12.
Conclusions:
- RXP470.1-based probes enable effective optical imaging of active MMP-12.
- This technology serves as a valuable tool for aneurysm pathophysiology research.
- The probes hold potential for drug development and future clinical applications.
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