Development of matrix metalloproteinase-targeted probes for lung inflammation detection with positron emission...

Area of Science:

• Biomedical Imaging
• Radiochemistry
• Molecular Imaging

Background:

• Matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-12, play a role in chronic obstructive pulmonary disease (COPD) pathogenesis.
• Targeted imaging probes are needed for non-invasive assessment of MMP activity in lung diseases.

Purpose of the Study:

• To develop and evaluate a novel radiofluorinated positron emission tomography (PET) probe, 18F-IPFP, for imaging MMPs in COPD.
• To assess the probe's affinity for MMP-12 and its efficacy in detecting MMP upregulation in a preclinical COPD model.

Main Methods:

• Design and synthesis of 18F-IPFP by modifying an MMP inhibitor with a radiofluorine label.
• Evaluation of IPFP's binding affinity for MMP-12 (IC50).
• Establishment of a mouse model of COPD induced by cigarette smoke exposure and assessment of lung MMP expression.

Main Results:

• 18F-IPFP demonstrated high affinity for MMP-12 (IC50 = 1.5 nM), outperforming existing PET probes.
• COPD mice showed significantly increased MMP-9 and MMP-12 expression in the lungs.
• Lung radioactivity accumulation of 18F-IPFP was 4x higher in COPD mice compared to normal mice and significantly higher than in other organs.

Conclusions:

• 18F-IPFP is a promising PET probe for pulmonary imaging of MMPs.
• The probe shows potential for early diagnosis, monitoring therapeutic response, and aiding drug development for MMP-related diseases.