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Published on: January 12, 2016
Molecular Imaging of Fibroblast Activity After Myocardial Infarction Using a 68Ga-Labeled Fibroblast Activation
Zohreh Varasteh1, Sarajo Mohanta2,3, Stephanie Robu4
1Department of Nuclear Medicine, Klinikum rechts der Isar der TUM, Munich, Germany zohreh.varasteh@tum.de.
Insights
New PET imaging using 68Ga-FAPI-04 effectively visualizes activated fibroblasts after myocardial infarction (MI). This tracer shows potential for monitoring cardiac remodeling and improving patient management following heart attacks.
Area of Science:
- Nuclear Medicine
- Cardiovascular Imaging
- Radiochemistry
Background:
- Heart failure is a significant complication following myocardial infarction (MI).
- Activated fibroblasts in the injured heart influence cardiac remodeling post-MI.
- Fibroblast Activation Protein (FAP) is a marker of activated fibroblasts.
Purpose of the Study:
- To assess the feasibility of using a novel 68Ga-labeled FAP inhibitor (68Ga-FAPI-04) for PET imaging of fibroblast activation.
- To evaluate 68Ga-FAPI-04 as a tool for monitoring cardiac remodeling after MI in a preclinical model.
Main Methods:
- Myocardial infarction (MI) and sham-operated rats underwent 68Ga-FAPI-04 PET/CT scans at multiple time points post-MI.
- Comparative 18F-FDG PET/CT scans were performed 3 days after MI.
- Ex vivo analyses included autoradiography, H&E staining, and immunofluorescence on harvested heart tissues.
Main Results:
- 68Ga-FAPI-04 uptake in the injured myocardium peaked at 6 days post-MI.
- Tracer accumulation was concentrated in the MI border zone, correlating with FAP-positive myofibroblast presence.
- Blocking studies demonstrated specific uptake, with minimal off-target accumulation.
Conclusions:
- 68Ga-FAPI-04 is a promising radiotracer for noninvasive in vivo imaging of post-MI fibroblast activation.
- This imaging approach may offer significant diagnostic and prognostic value for managing patients after MI.
- Monitoring activated fibroblasts could enhance understanding and treatment of cardiac remodeling.
Abstract:
Heart failure remains a major source of late morbidity and mortality after myocardial infarction (MI). The temporospatial presence of activated fibroblasts in the injured myocardium predicts the quality of cardiac remodeling after MI. Therefore, monitoring of activated fibroblasts is of great interest for studying cardiac remodeling after MI. Fibroblast activation protein (FAP) expression is upregulated in activated fibroblasts. This study investigated the feasibility of imaging activated fibroblasts with a new 68Ga-labeled FAP inhibitor (68Ga-FAPI-04) for PET imaging of fibroblast activation in a preclinical model of MI. Methods: MI and sham-operated rats were scanned with 68Ga-FAPI-04 PET/CT (1, 3, 6, 14, 23, and 30 d after MI) and with 18F-FDG (3 d after MI). Dynamic 68Ga-FAPI-04 PET and blocking studies were performed on MI rats 7 d after coronary ligation. After in vivo scans, the animals were euthanized and their hearts harvested for ex vivo analyses. Cryosections were prepared for autoradiography, hematoxylin and eosin (H&E), and immunofluorescence staining. Results:68Ga-FAPI-04 uptake in the injured myocardium peaked on day 6 after coronary ligation. The tracer accumulated intensely in the MI territory, as identified by decreased 18F-FDG uptake and confirmed by PET/MR and H&E staining. Autoradiography and H&E staining of cross-sections revealed that 68Ga-FAPI-04 accumulated mainly at the border zone of the infarcted myocardium. In contrast, there was only minimal uptake in the infarct of the blocked rats, comparable to the uptake in the remote noninfarcted myocardium (PET image-derived ratio of infarct uptake to remote uptake: 6 ± 2). Immunofluorescence staining confirmed the presence of FAP-positive myofibroblasts in the injured myocardium. Morphometric analysis of the whole-heart sections demonstrated 3- and 8-fold higher FAP-positive fibroblast density in the border zone than in the infarct center and remote area, respectively. Conclusion:68Ga-FAPI-04 represents a promising radiotracer for in vivo imaging of post-MI fibroblast activation. Noninvasive imaging of activated fibroblasts may have significant diagnostic and prognostic value, which could aid clinical management of patients after MI.
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