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Updated: May 27, 2026
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
Early diagnosis of arthritis in mice with collagen-induced arthritis, using a fluorogenic matrix metalloproteinase
Ju Hee Ryu1, Aeju Lee, Jun-Uk Chu
1Korea Institute of Science and Technology, Seoul, and Seoul National University, Seoul, Republic of Korea.
Objective:
Early treatment based on an early diagnosis of rheumatoid arthritis (RA) could halt progression of the disease, but early diagnosis is often difficult. Matrix metalloproteinase 3 (MMP-3) is thought to be particularly important in the pathogenesis of RA. The aim of this study was to investigate whether an MMP-3-specific polymeric probe could be used for early diagnosis and for visualizing the progression of arthritis, using a near-infrared fluorescence (NIRF) imaging system.
Methods:
The MMP-3-specific polymeric probe was developed by conjugating NIRF dye, MMP substrate peptide, and dark quencher to self-assembled chitosan nanoparticles. One hour after intravenous administration of the probe, fluorescent images of mice with collagen-induced arthritis at different stages of disease development were obtained. The correlation between the fluorescence recovered in in vivo imaging when using an MMP-3-specific polymeric probe and up-regulated MMP-3 activity in the joint tissues was evaluated by Western blotting and immunohistochemical staining. Histologic analysis and micro-computed tomography (micro-CT) were also used to assess arthritis progression.
Results:
A significantly higher NIRF signal was recovered from arthritic joints compared with normal joints at 14 days after the first immunization, before any erythema or swelling could be observed with the naked eye or any erosion was detected by histologic analysis or micro-CT. The results of immunohistochemical analysis and Western blotting confirmed that the fluorescence recovered in the in vivo imaging was related to up-regulated MMP-3 activity in the joint tissues.
Conclusion:
An MMP-3-specific polymeric probe provided clear early diagnosis of arthritis and visualization of arthritis progression using an NIRF imaging system. This approach could be used for early diagnosis and for monitoring drug and surgical therapies in individual cases.
Insights
A novel polymeric probe targeting matrix metalloproteinase 3 (MMP-3) enables early rheumatoid arthritis (RA) diagnosis. This near-infrared fluorescence (NIRF) imaging approach visualizes arthritis progression before clinical signs appear.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Rheumatology
Background:
- Early diagnosis of rheumatoid arthritis (RA) is crucial for halting disease progression but remains challenging.
- Matrix metalloproteinase 3 (MMP-3) plays a significant role in RA pathogenesis.
Purpose of the Study:
- To develop and evaluate an MMP-3-specific polymeric probe for early RA diagnosis.
- To assess the probe's utility in visualizing arthritis progression using near-infrared fluorescence (NIRF) imaging.
Main Methods:
- A polymeric probe was synthesized by conjugating NIRF dye, MMP substrate peptide, and dark quencher to chitosan nanoparticles.
- The probe was administered intravenously to mice with collagen-induced arthritis, and NIRF imaging was performed.
- Correlation of fluorescence signals with MMP-3 activity was confirmed via Western blotting and immunohistochemistry; arthritis progression was assessed using histology and micro-CT.
Main Results:
- Significantly elevated NIRF signals were detected in arthritic joints 14 days post-immunization, preceding visible swelling or erosions.
- Immunohistochemistry and Western blotting confirmed the fluorescence signal's direct relationship to upregulated MMP-3 activity.
- The probe successfully visualized arthritis progression in vivo.
Conclusions:
- An MMP-3-specific polymeric probe combined with NIRF imaging facilitates early RA diagnosis and monitoring of disease progression.
- This innovative approach holds potential for personalized monitoring of therapeutic interventions in RA.
