Feasibility of 68Ga-FAPI-46 PET for evaluating fibrosis activity in aortic aneurysm

Abstract Purpose Fibroblast activation protein (FAP) expression is upregulated in tissue fibrosis, active inflammation, and tumors. Aortic aneurysm (AA) is a disease where aortic wall loses its elasticity with fibrotic change. We investigated the feasibility of 68Ga-labelled FAP inhibitor (FAPI) PET and its quantitative indexes, as a non-invasive imaging for evaluating fibrosis activity in AA. Methods Twenty patients with AA who were planned for aneurysmal resection were prospectively enrolled. 68Ga-FAPI-46 PET was preoperatively performed to examine FAP expression in the AA. Nine 68Ga-FAPI-46 PET cases from lung cancer patients were used as control. Expressions of FAP and other markers in the resected AA tissue and remote aorta were assessed by western blotting. 68Ga-FAPI-46 PET was evaluated visually, and quantitatively using SUV and target-to-liver ratio (TLR). The image findings and quantitative indexes were compared with the clinicopathologic factors. Results When AA tissues were divided into tertiles according to the visual grading of PET, the quantitative indexes showed significant differences among groups (Low 2.07±0.36 vs. Moderate 2.80±0.47 vs. High 3.55±0.37, p=0.002 for SUVmax; Low 2.37±0.57 vs. Moderate 2.81±1.16 vs. High 4.44±0.13, p=0.042 for TLR). Quantitative indexes of FAPI PET were significantly higher in AA patients compared to control group (1.99±0.36 vs. 2.51±0.67, p=0.048 for SUVmax; 2.10±0.71 vs. 2.81±1.03, p=0.038 for TLR). On western blotting, the AA tissue showed variable but overall increased FAP expression compared to the remote aorta (p=0.012). The quantitative indexes of FAPI PET were significantly correlated with the degree of FAP expression on western blotting (rho=0.75, p=0.0020 for SUVmax; rho=0.68, p=0.0070 for TLR). CT growth rate was significantly different among groups (Low -0.0051±0.011 vs. Moderate 0.0074±0.00947 vs. High 0.034±0.043, p=0.037) and positive correlation was found between CT growth rate and SUVmax (rho=0.53, p=0.043). No significant correlation was found between the indexes and other markers including smooth muscle proliferation (a-SMA) or inflammation (TGF-b). Conclusion AA tissues show variable but overall increased FAP expression. The quantitative indexes of FAPI PET are well correlated with the FAP expression on the tissue. FAPI PET can be an effective non-invasive imaging for evaluating fibrosis activity of AA, and further studies are warranted to assess clinical implication of fibrosis activity in the AA.