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Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
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Dual-functional, receptor-targeted fluorogenic probe for in vivo imaging of extracellular protease expressions
Lei Zhu1, Jin Xie, Magdalena Swierczewska
1National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Maryland 20892, United States.
Abstract:
Herein, we report a new type of in vivo fluorogenic probe that enables simultaneous and active targeting of overexpressed receptors, α(V)β(3) integrins, and extracellular proteases, matrix metalloproteinases (MMPs), in the tumor regions. This c(RGDyK)-conjugated MMP fluorogenic probe efficiently targets the tumor regions with high retention time while maintaining receptor binding affinity and substrate activity. The probe minimizes nonspecific accumulation, thus demonstrating improved tumor-to-background signal ratio (T/N) in both α(V)β(3) integrin- and MMP-overexpressing U87MG tumor-bearing mouse model. This strategy can be easily tuned for a wide array of applications targeting various receptors and extracellular proteases in vivo.
Insights
Researchers developed a novel in vivo fluorogenic probe for simultaneous targeting of alpha(V)beta(3) integrins and matrix metalloproteinases (MMPs) in tumors. This probe enhances tumor visualization by minimizing background signals for improved diagnostic potential.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Cancer Diagnostics
Background:
- Overexpressed alpha(V)beta(3) integrins and matrix metalloproteinases (MMPs) are key biomarkers in tumor regions.
- Simultaneous targeting of multiple tumor biomarkers can improve diagnostic accuracy and therapeutic strategies.
- Existing imaging probes often suffer from nonspecific accumulation and low tumor-to-background ratios.
Purpose of the Study:
- To develop a novel in vivo fluorogenic probe for simultaneous and active targeting of alpha(V)beta(3) integrins and MMPs.
- To evaluate the probe's efficiency in targeting tumor regions and maintaining binding affinity and substrate activity.
- To assess the probe's performance in minimizing nonspecific accumulation and improving tumor-to-background signal ratio (T/N).
Main Methods:
- Conjugation of c(RGDyK) peptide to an MMP-cleavable fluorogenic substrate.
- In vivo administration of the c(RGDyK)-conjugated MMP fluorogenic probe.
- Evaluation of probe targeting, retention time, binding affinity, substrate activity, and T/N ratio in U87MG tumor-bearing mouse models.
Main Results:
- The c(RGDyK)-conjugated MMP fluorogenic probe efficiently targeted tumor regions with high retention.
- The probe maintained both alpha(V)beta(3) integrin binding affinity and MMP substrate activity.
- Improved T/N ratios were observed, indicating minimized nonspecific accumulation in U87MG tumor models.
Conclusions:
- A new class of in vivo fluorogenic probes enables simultaneous targeting of alpha(V)beta(3) integrins and MMPs.
- This probe strategy offers enhanced tumor visualization with improved T/N ratios.
- The tunable strategy holds potential for diverse in vivo applications targeting various receptors and proteases.
