Abstract
Background and Rationale: After acute myocardial infarction (AMI), fibroblast activation protein (FAP) upregulation exceeds the infarct region. We sought further insights into the physiologic relevance by correlating FAP-targeted PET with tissue characteristics from cardiac magnetic resonance (CMR) and functional outcome. Methods: Thirty-five patients underwent CMR, perfusion SPECT, and 68Ga-FAPI-46 PET/CT within 11 days after AMI. Infarct size was determined from SPECT by comparison to reference database. For PET, regional standardized uptake values (SUV) and isocontour volumes-of-interest (VOI) determined the extent of cardiac FAP upregulation (FAP-volume). CMR yielded functional parameters, area of injury (late gadolinium enhancement, LGE) and T1/T2 mapping. Follow-up was available from echocardiography or CMR after 139.5 (IQR 80.5-188.25) days (n = 14). Results: The area of FAP-upregulation was significantly larger than SPECT perfusion defect size (58±15 vs. 23±17%, p<0.001) and infarct area by LGE (28±11%, p<0.001). FAP-volume significantly correlated with CMR parameters at baseline (all p<0.001): infarct area (r=0.58), left ventricular (LV) mass (r=0.69), endsystolic (r=0.62) and enddiastolic volume (r=0.57). Segmental analysis revealed FAP-upregulation in 308/496 myocardial segments (62%). Significant LGE was found in only 56% of FAP-positive segments, elevated T1 in 74%, and elevated T2 in 68%. 14% (44/308) of FAP-positive segments exhibited neither prolonged T1 or T2 nor significant LGE. Of note, FAP-volume correlated only weakly with simultaneously measured left ventricular ejection fraction (LVEF) at baseline (r=-0.32, P = 0.07), whereas there was a significant inverse correlation with LVEF obtained at later follow-up (r=-0.58, P = 0.007). Conclusion: Early after AMI and reperfusion therapy, activation of fibroblasts markedly exceeds the hypoperfused infarct region and involves non-infarcted myocardium. The 68Ga-FAPI PET signal does not match regional myocardial tissue characteristics as defined by CMR, but it is predictive of the evolution of ventricular dysfunction. FAP-targeted imaging may provide a novel biomarker of left ventricular remodeling that is complementary to existing techniques.
- Cardiology (clinical)
- Molecular Imaging
- PET
- fibroblast activation protein
- left ventricular remodeling
- myocardial infarction
- positron emission tomography
- Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.