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Updated: Aug 5, 2025
MRI and PET in Mouse Models of Myocardial Infarction
Published on: December 19, 2013
Myeloperoxidase PET Imaging Tracks Intracellular and Extracellular Treatment Changes in Experimental Myocardial
Matthias W G Zeller1,2, Cuihua Wang1,2, Edmund J Keliher2,3
1Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02129, USA.
Abstract:
Myeloperoxidase (MPO) is a highly oxidative, pro-inflammatory enzyme involved in post-myocardial infarction (MI) injury and is a potential therapeutic target. While multiple MPO inhibitors have been developed, the lack of an imaging reporter to select appropriate patients and assess therapeutic efficacy has hampered clinical development. Thus, a translational imaging method to detect MPO activity non-invasively would help to better understand the role MPO plays in MI and facilitate novel therapy development and clinical validation. Interestingly, many MPO inhibitors affect both intracellular and extracellular MPO, but previous MPO imaging methods can only report extracellular MPO activity. In this study, we found that an MPO-specific PET imaging agent (18F-MAPP) can cross cell membranes to report intracellular MPO activity. We showed that 18F-MAPP can track the treatment effect of an MPO inhibitor (PF-2999) at different doses in experimental MI. The imaging results were corroborated by ex vivo autoradiography and gamma counting data. Furthermore, extracellular and intracellular MPO activity assays revealed that 18F-MAPP imaging can report the changes induced by PF-2999 on both intracellular and extracellular MPO activities. These findings support 18F-MAPP as a translational candidate to noninvasively report MPO activity and accelerate drug development against MPO and other related inflammatory targets.
Insights
A new PET imaging agent, 18F-MAPP, can non-invasively detect intracellular myeloperoxidase (MPO) activity, aiding in tracking MPO inhibitor efficacy for myocardial infarction (MI) treatment.
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.
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