Staging Liver Fibrosis by Fibroblast Activation Protein Inhibitor PET in a Human-Sized Swine Model

Abstract

Current methods of staging liver fibrosis have notable limitations. We investigated the utility of PET in staging liver fibrosis by correlating liver uptake of ⁶⁸Ga-labeled fibroblast activation protein inhibitor (FAPI) with histology in a human-sized swine model. Methods: Five pigs underwent baseline ⁶⁸Ga-FAPI-46 (⁶⁸Ga-FAPI) PET/MRI and liver biopsy, followed by liver parenchymal embolization, 8 wk of oral alcohol intake, endpoint ⁶⁸Ga-FAPI PET/MRI, and necropsy. Regions of interest were drawn on baseline and endpoint PET images, and SUV_mean was recorded. At the endpoint, liver sections corresponding to regions of interest were identified and cut out. Fibrosis was histologically evaluated using a modified METAVIR score for swine liver and quantitatively using collagen proportionate area (CPA). Box-and-whisker plots and linear regression were used to correlate SUV_mean with METAVIR score and CPA, respectively. Results: Liver ⁶⁸Ga-FAPI uptake strongly correlated with CPA (r = 0.89, P < 0.001). ⁶⁸Ga-FAPI uptake was significantly and progressively higher across F2 and F3/F4 fibrosis stages, with a respective median SUV_mean of 2.9 (interquartile range [IQR], 2.7–3.8) and 7.6 (IQR, 6.7–10.2) (P < 0.001). There was no significant difference between ⁶⁸Ga-FAPI uptake of baseline liver and endpoint liver sections staged as F0/F1, with a respective median SUV_mean of 1.7 (IQR, 1.3–2.0) and 1.7 (IQR, 1.5–1.8) (P = 0.338). Conclusion: The strong correlation between liver ⁶⁸Ga-FAPI uptake and the histologic stage of liver fibrosis suggests that ⁶⁸Ga-FAPI PET can play an impactful role in noninvasive staging of liver fibrosis, pending validation in patients.