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

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.