Radioactive smart probe for potential corrected matrix metalloproteinase imaging

Area of Science:

• Biomedical imaging
• Molecular imaging
• Biochemistry

Background:

• Optical imaging probes for metalloproteinase (MMP) activity lack precise quantification due to signal scattering and limited depth penetration.
• Accurate in vivo enzyme activity measurement is crucial for effective tumor diagnosis and treatment monitoring.

Purpose of the Study:

• To develop and validate a novel activatable peptide probe for detecting tumor MMP activity.
• To demonstrate the feasibility of correcting optical imaging data with Positron Emission Tomography (PET) for accurate MMP activity quantification.

Main Methods:

• A novel activatable peptide probe, (64)Cu-BBQ650-PLGVR-K(Cy5.5)-E-K(DOTA)-OH, was synthesized and characterized.
• In vitro and in vivo studies were conducted to confirm MMP specificity and evaluate imaging performance.
• A dual-modality imaging approach combining optical imaging and PET was employed.

Main Results:

• The probe exhibited quenched fluorescence in its native state, releasing strong fluorescence upon enzymatic cleavage by target MMPs.
• MMP specificity was confirmed in both in vitro and in vivo experiments.
• The study successfully demonstrated the feasibility of correcting optical imaging data using PET signals for quantitative MMP activity assessment.

Conclusions:

• The developed activatable probe and dual-modality imaging strategy offer an accurate method for visualizing and quantifying tumor MMP activity.
• This approach overcomes the limitations of optical imaging and provides a new avenue for protease imaging in oncology.
• The strategy holds potential for application in imaging other protease activities beyond MMPs.