Abstract

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 18F-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 [18F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) (n = 3), [18F]fluoroacetate ([18F]FAc) (n = 3), and 18F-fluoro-2-deoxy-D-glucose ([18F]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 [18F]FEPPA and [18F]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 [18F]FAc in the liver was not significantly different before and after BDL (P = 0.28). Collectively, both [18F]FEPPA and [18F]FDG can serve as sensitive probes for detecting the liver fibrosis. However, [18F]FAc is not recommended to diagnose liver fibrosis.

Highlights

  • Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), is a global health concern, with a rising prevalence in Asia [1]

  • As NASH may irreversibly progress from fibrosis to cirrhosis, the accurate and rapid assessment of liver condition plays a crucial role in formulating effective therapeutic plans

  • The common bile duct was significantly dilated after bile duct ligation (BDL) on MR images, and the bile duct appeared hyperintense after BDL surgery on both T1W and T2W imaging, suggesting that the increased T1 and T2 values were associated with successful establishment of liver fibrosis [20]

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Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), is a global health concern, with a rising prevalence in Asia [1]. As NASH may irreversibly progress from fibrosis to cirrhosis, the accurate and rapid assessment of liver condition plays a crucial role in formulating effective therapeutic plans. Liver biopsy has been considered the gold standard for the assessment of fibrosis. Translocator protein (18 kDa) (TSPO), known as peripheral benzodiazepine receptor, is located on the outer membrane of mitochondria and is expressed in various peripheral organs but relatively low in the normal liver [3]. The liver of NASH patients has increased mitochondrial mass and biosynthesis due to adaptive stress response [4]. Hatori et al indicated that the elevated accumulation of [18F]FEDAC in a chronic carbon tetrachloride-treated fibrotic liver was noticed when compared to controls [6]. TSPO is increased during the inflammation process, which is considered a common feature observed in chronic liver diseases

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