Related Experiment Video
Updated: Jun 25, 2026
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
Atherosclerosis and matrix metalloproteinases: experimental molecular MR imaging in vivo
Vardan Amirbekian1, Juan Gilberto S Aguinaldo, Smbat Amirbekian
1Translational and Molecular Imaging Institute, Department of Radiology, Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Schoolof Medicine, New York, NY 10029, USA.
Purpose:
To evaluate the capability of P947, a magnetic resonance (MR) imaging contrast agent that molecularly targets matrix metalloproteinases (MMPs), to aid detection and imaging of MMPs in atherosclerotic lesions in vivo; its specificity compared with that of P1135; expression and distribution of MMPs in atherosclerotic vessels; and in vivo distribution and molecular localization of fluorescent europium (Eu) P947.
Materials And Methods:
The Animal Care and Use Committee approved all experiments. P947 was synthesized by attaching a gadolinium chelate (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) to a peptide that specifically binds MMPs. Scrambled form of P947 (P1135) was synthesized by replacing the targeting moiety of P947 with a scrambled peptide lacking the ability to bind MMPs. P947, P1135, and gadoterate meglumine were injected into atherosclerotic apolipoprotein E-deficient and wild-type mice. The aortic MR imaging enhancement produced by the contrast agents was measured at different times and was compared by using one-way analysis of variance. MMP expression was investigated in the aortas by using MMP immunostaining and in situ MMP zymography. A fluorescent form of P947 (Eu-P947) was synthesized to compare the in vivo distribution of the contrast agent (Eu-P947) with specific MMP immunofluorescent staining.
Results:
MMP-targeted P947 facilitated a 93% increase (P < .001) in MR image signal intensity (contrast-to-noise ratio [CNR], 17.7 compared with 7.7; P < .001) of atherosclerotic lesions in vivo. Nontargeted P1135 (scrambled P947) provided 33% MR image enhancement (CNR, 10.8), whereas gadoterate meglumine provided 5% (CNR, 6.9). Confocal laser scanning microscopy demonstrated colocalization between fluorescent Eu-P947 and MMPs in atherosclerotic plaques. Eu-P947 was particularly present in the fibrous cap region of plaques.
Conclusion:
P947 improved MR imaging for atherosclerosis through MMP-specific targeting. The results were validated and provide support for further assessment of P947 as a potential tool for the identification of unstable atherosclerosis.
Insights
A novel magnetic resonance imaging contrast agent, P947, effectively targets matrix metalloproteinases (MMPs) in atherosclerotic lesions. This MMP-specific agent significantly enhances imaging, aiding in the identification of unstable atherosclerosis.
Area of Science:
- Biomedical Imaging
- Cardiovascular Research
- Molecular Imaging
Background:
- Atherosclerosis involves matrix metalloproteinases (MMPs) that degrade extracellular matrix.
- Accurate imaging of MMPs is crucial for identifying vulnerable atherosclerotic plaques.
Purpose of the Study:
- To assess P947, a novel MR imaging contrast agent targeting MMPs, for detecting MMPs in atherosclerotic lesions.
- To compare the specificity of P947 with a non-targeted agent (P1135).
- To investigate MMP expression and distribution in atherosclerotic vessels and the in vivo localization of P947.
Main Methods:
- Synthesis of P947 (MMP-targeting) and P1135 (scrambled control) contrast agents.
- MR imaging of atherosclerotic mice after injection of P947, P1135, or gadoterate meglumine.
- Analysis of aortic MR imaging enhancement using ANOVA.
- MMP expression analysis via immunostaining and zymography.
- In vivo distribution studies using fluorescent Eu-P947.
Main Results:
- P947 significantly increased MR signal intensity in atherosclerotic lesions by 93% (CNR 17.7).
- Non-targeted P1135 and gadoterate meglumine showed lesser enhancement (33% and 5%, respectively).
- Fluorescent Eu-P947 colocalized with MMPs in plaques, particularly in the fibrous cap region.
Conclusions:
- P947 enhances MR imaging of atherosclerosis through specific MMP targeting.
- These findings support P947 as a promising tool for identifying unstable atherosclerotic lesions.
