Myeloperoxidase PET Imaging Tracks Intracellular and Extracellular Treatment Changes in Experimental Myocardial...

Area of Science:

• Biomedical imaging
• Cardiovascular research
• Enzyme activity detection

Background:

• Myeloperoxidase (MPO) is a key pro-inflammatory enzyme in post-myocardial infarction (MI) injury.
• MPO inhibitors are potential therapeutics, but clinical development is hindered by a lack of imaging reporters.
• Existing imaging methods primarily detect extracellular MPO activity, missing intracellular MPO roles.

Purpose of the Study:

• To develop a translational imaging method for non-invasive MPO activity detection.
• To assess the capability of a novel PET imaging agent, 18F-MAPP, in reporting both intracellular and extracellular MPO activity.
• To evaluate 18F-MAPP's utility in tracking MPO inhibitor treatment effects in experimental MI.

Main Methods:

• Development and characterization of 18F-MAPP, an MPO-specific PET imaging agent.
• In vivo imaging of experimental MI models treated with an MPO inhibitor (PF-2999).
• Ex vivo validation using autoradiography and gamma counting, alongside MPO activity assays.

Main Results:

• 18F-MAPP successfully crossed cell membranes to report intracellular MPO activity.
• PET imaging with 18F-MAPP effectively tracked the dose-dependent effects of the MPO inhibitor PF-2999 in experimental MI.
• Imaging findings were consistent with ex vivo analyses and MPO activity assays, confirming detection of both intracellular and extracellular MPO changes.

Conclusions:

• 18F-MAPP is a promising PET imaging agent for non-invasively reporting MPO activity.
• This agent can assess both intracellular and extracellular MPO activity, crucial for understanding MPO's role in MI.
• 18F-MAPP can accelerate MPO-targeted drug development and clinical validation for inflammatory diseases.