Fibroblast Activation Protein Acts as a Biomarker for Monitoring ECM Remodeling During Aortic Aneurysm via 68Ga-FAPI-04 PET Imaging

  • Adv Sci (Weinh). 2025 Apr;12(14):e2411152. doi: 10.1002/advs.202411152.
Chengkai Hu  1 ,  Hui Tan  2 ,  Yuchong Zhang  1 ,  Genmao Cao  1 ,  Chenye Wu  3 ,  Peng Lin  1 ,  Shouji Qiu  1 ,  Fandi Mo  1 ,  Enci Wang  1 ,  Shiyi Li  1 ,  Tong Yuan  1 ,  Zheyun Li  1 ,  Weiguo Fu  1  4  5 ,  Dengfeng Cheng  2 ,  Hao Lai  3 ,  Xiaoyuan Chen  6  7  8  9  10 ,  Lixin Wang  1  4  5
Affiliations
  • 1. Department of Vascular Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
  • 2. Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
  • 3. Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
  • 4. Department of Vascular Surgery (Xiamen), Zhongshan hospital, Fudan University, Xiamen, 361015, China.
  • 5. Xiamen Municipal Vascular Disease Precise Diagnose & Treatment Lab, Xiamen, 361015, China.
  • 6. Departments of Diagnostic Radiology, Chemical and Biomolecular Engineering, Biomedical Engineering, Pharmacy and Pharmaceutical Sciences, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, 119074, Singapore.
  • 7. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore.
  • 8. Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
  • 9. Theranostics Center of Excellence (TCE), Yong Loo Lin School of Medicine, National University of Singapore, 11 Biopolis Way, Helios, Singapore, 138667, Singapore.
  • 10. Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore.
PMID: 39950910 DOI: 10.1002/advs.202411152
Abstract

Traditional imaging modalities used to monitor the diameter of aortic aneurysms (AAs) often fail to follow pathological progression. Fibroblast activation protein (FAP), a key regulator of extracellular matrix (ECM) remodeling, plays a pivotal role in aortic disease. However, its expression in the aortic wall during aneurysm progression and its potential correlation with disease severity remains unexplored. Here, utilizing histology the levels of FAP are higher in the aortic wall of patients with AA compared to healthy controls. In three distinct animal models of AA, a progressive increase in FAP expression, coincides with the advancement of ECM remodeling. Notably, the levels of 68Ga-FAPI-04 uptake in a rabbit model of abdominal AA (AAA) is positively correlated with aortic dilation (r = 0.84, p < 0.01), and the histological examination further confirmed that regions of high 68Ga-FAPI-04 uptake exhibited both increased FAP expression and more severe pathological changes. The 68Ga-FAPI-04 imaging in AA patients showed that the radiotracer specifically accumulated in the aortic walls of persistently dilated AA. These findings suggest that 68Ga-FAPI-04 positron emission tomographic (PET) imaging, by visualizing FAP localization, allows for a non-invasive approach to potentially monitor ECM remodeling during the AA progression.

Keywords
aortic aneurysm; extracellular matrix; fibroblast activation protein; positron emission tomography imaging.
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