Molecular imaging of fibroblast activity in pressure overload heart failure using [68 Ga]Ga-FAPI-04 PET/CT
- 29 September 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in European Journal of Nuclear Medicine and Molecular Imaging
- Vol. 50 (2), 465-474
- https://doi.org/10.1007/s00259-022-05984-6
Abstract
Purpose We aimed to evaluate whether [68 Ga]Ga-FAPI-04 PET/CT could characterize the early stages of cardiac fibrosis in pressure overload heart failure. Methods Sprague–Dawley rats underwent abdominal aortic constriction (AAC) (n = 12) and sham surgery (n = 10). All rats were scanned with [68 Ga]Ga-FAPI-04 PET/CT at 2, 4, and 8 weeks after surgery. The expression of fibroblast activation protein (FAP) in the myocardium was detected by immunohistochemistry. [68 Ga]Ga-FAPI-04 PET signal and FAP expression were compared between two groups. Results Compared with the sham group, the AAC group presented with decreased ejection fraction (EF) and fractional shortening (FS) and increased left ventricular internal dimensions in diastole (LVIDd) and systole (LVIDs) at 4 and 8 weeks (all p < 0.01). The AAC group showed higher [68 Ga]Ga-FAPI-04 accumulation in the heart than the sham group at 2, 4, and 8 weeks, and FAPI increased significantly from 2 to 8 weeks (all p < 0.001). Immunohistochemistry confirmed the higher density of the FAP+ area in the AAC group. The intensity of the [68 Ga]Ga-FAPI-04 correlated with the density of the FAP+ area (p < 0.001). The expression of the [68 Ga]Ga-FAPI-04 at 4 weeks correlated with the deterioration of cardiac function at 8 weeks (EF: R = − 0.87; FS: R = − 0.72; LVIDd: R = 0.77; LVIDs: R = 0.79; all p < 0.001). The AAC group also showed an increased [68 Ga]Ga-FAPI-04 signal in the liver, peaking at 4 weeks and then declining. Cardiac and liver PET signals correlated at 4 weeks in the AAC group (R = 0.69, p = 0.0010), suggesting an early fibrotic link between organs. A combination of the [68 Ga]Ga-FAPI-04 intensity in the heart and liver at 4 weeks better predicted the deterioration of cardiac function at 8 weeks. Conclusions The activated fibroblasts in the heart and liver after pressure overload can be monitored by [68 Ga]Ga-FAPI-04 PET/CT, which reveals an early fibrotic link in cardio-liver interactions and could better predict nonischemic heart failure prognosis.Keywords
Funding Information
- “234 Discipline Climbing Plan” of the First Affiliated Hospital of Naval Medical University (2019YPT002, 2020YPT002)
- shanghai science and technology innovation action plan “science and technology support project in biomedical science” (21S11906000)
This publication has 25 references indexed in Scilit:
- Development of Quinoline-Based Theranostic Ligands for the Targeting of Fibroblast Activation ProteinJournal of Nuclear Medicine, 2018
- A Tumor-Imaging Method Targeting Cancer-Associated FibroblastsJournal of Nuclear Medicine, 2018
- Association of Liver Fibrosis With Cardiovascular Diseases in the General PopulationCirculation: Cardiovascular Imaging, 2018
- Epidemiology of heart failure with preserved ejection fractionNature Reviews Cardiology, 2017
- A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in RatsJournal of Visualized Experiments, 2016
- Relevance of mouse models of cardiac fibrosis and hypertrophy in cardiac researchMolecular and Cellular Biochemistry, 2016
- Defining the Cardiac FibroblastCirculation Journal, 2016
- Myocardial Collagen Cross-Linking Is Associated With Heart Failure Hospitalization in Patients With Hypertensive Heart FailureJournal of Invasive Cardiology, 2016
- Prognostic Significance of Myocardial Fibrosis Quantification by Histopathology and Magnetic Resonance Imaging in Patients With Severe Aortic Valve DiseaseJournal of Invasive Cardiology, 2010
- Cardiac fibroblasts: At the heart of myocardial remodelingPharmacology & Therapeutics, 2009