Comparison of (18)F-FDG, (18)F-Fluoroacetate, and (18)F-FEPPA for Imaging Liver Fibrosis in a Bile Duct-Ligated Rat Model

Developing sensitive diagnostic methods for a longitudinal evaluation of the status of liver fibrosis is a priority. This study is aimed at assessing the significance of longitudinal positron emission tomography (PET) imaging with (18)F-labeling tracers for assessing liver fibrosis in a rat model with bile duct ligation (BDL). Twenty-one 6-week-old Sprague-Dawley male rats were used in this study. Longitudinal PET images using [(18)F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([(18)F]FEPPA) (n = 3), [(18)F]fluoroacetate ([(18)F]FAc) (n = 3), and 18F-fluoro-2-deoxy-D-glucose ([(18)F]FDG) (n = 3) were obtained at 0, 1, and 2 weeks after BDL. Biochemical assays, histological assays, immunohistochemical staining assays, and next generation sequencing analyses were also performed at 0 (n = 3), 1 (n = 3), 2 (n = 3), and 3 (n = 3) weeks after BDL, which demonstrated the severe damage in rat livers after BDL. Regarding [(18)F]FEPPA and [(18)F]FDG, there was a significantly higher uptake in the liver after BDL (both P < 0.05), which lasted until week 2. However, the uptake of [(18)F]FAc in the liver was not significantly different before and after BDL (P = 0.28). Collectively, both [(18)F]FEPPA and [(18)F]FDG can serve as sensitive probes for detecting the liver fibrosis. However, [(18)F]FAc is not recommended to diagnose liver fibrosis.