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

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.

SUBMITTER: Wu CY

PROVIDER: S-EPMC8654319 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Wu Chun-Yi CY Hsieh Hsin-Hua HH Chu Pei-An PA Hong Wen-Hsiang WH Chang Ting-Yu TY Hsu Chia-Fang CF Lin Siao-Ting ST Su Po-Hsun PH Peng Shin-Lei SL

Molecular imaging 20211127

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-phenoxypyri ...[more]

PMID: 34934405

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Project description:BackgroundCoffee consumption has been shown to reduce the risk of liver fibrosis and is capable of inducing human UDP-glucuronosyltransferase (UGT) 1A genes. UGT1A enzymes act as indirect antioxidants catalyzing the elimination of reactive metabolites, which in turn are potent initiators of profibrotic mechanisms. The aim of this study was to analyze the role of UGT1A genes as effectors of the protective properties of coffee in bile duct ligation (BDL) induced liver fibrosis.MethodsFourteen days BDL with and without coffee pre- and co-treatment was performed in htgUGT1A-WT and htgUGT1A-SNP mice. Hepatic UGT1A mRNA expression levels, serum bilirubin and aminotransferase activities were determined. Liver fibrosis was assessed by collagen deposition, computational analysis of Sirius red tissue staining and expression of profibrotic marker genes. Oxidative stress was measured by hepatic peroxidase concentrations and immunofluorescence staining.ResultsUGT1A transcription was differentially activated in the livers of htgUGT1A-WT mice after BDL, in contrast to a reduced or absent induction in the presence of SNPs. Co-treated (coffee + BDL) htgUGT1A-WT-mice showed significantly increased UGT1A expression and protein levels and a considerably higher induction compared to water drinking WT mice (BDL), whereas in co-treated htgUGT1A-SNP mice absolute expression levels remained below those observed in htgUGT1A-WT mice. Collagen deposition, oxidative stress and the expression of profibrotic markers inversely correlated with UGT1A expression levels in htgUGT1A-WT and SNP mice after BDL and coffee + BDL co-treatment.ConclusionsCoffee exerts hepatoprotective and antioxidative effects via activation of UGT1A enzymes. Attenuated hepatic fibrosis as a result of coffee-mediated UGT1A induction during cholestasis was detected, while the protective action of coffee was lower in a common low-function UGT1A SNP haplotype present in 10% of the Caucasian population. This study suggests that coffee consumption might constitute a potential strategy to support the conventional treatment of cholestasis-related liver diseases.

Project description:BackgroundCirculating cirrhotic endothelial progenitor cells (EPC) interact with both liver sinusoidal endothelial cells (LSEC) and hepatic stellate cells (HSC) and promote angiogenesis in vitro. This study evaluated the effect of cirrhotic and control EPCs on hepatic angiogenesis, microcirculation, and fibrosis in vivo in rat models of cirrhosis.MethodologyAnimal models of cirrhosis were prepared by bile duct ligation (BDL). Circulating EPCs isolated from healthy human and cirrhotic blood were characterized by flow cytometry, cultured and administered through the tail vein in BDL rats after 2 weeks of ligation. The cells were given thrice a week for 2 weeks. The untreated group of BDL rats received only saline. Fibrosis was evaluated by Masson's trichrome staining. Dedifferentiated LSECs were identified by the expression of CD31, and activated HSCs were marked as alpha-SMA-positive cells and were studied by immunohistochemistry and western blotting in saline-, healthy EPC-, and cirrhotic EPC-treated rats. In vivo, hepatic and systemic hemodynamic parameters were evaluated. Liver functions were evaluated.ResultsIn comparison to controls, BDL rats revealed an increase of fibrosis and angiogenesis. Among the treated rats, cirrhotic EPC-treated rats had increased fibrosis grade as compared to healthy EPC-treated and saline-treated rats. There was an increase of both fibrosis and angiogenesis markers, alpha-SMA and CD31 in cirrhotic EPC-treated rats as compared to healthy EPC-treated and saline-treated rats in immunohistochemistry and western blot studies. Cirrhotic EPC-treated BDL rats had high portal pressure and portal blood flow with significantly elevated hepatic vascular resistance in comparison with healthy EPC- and saline-treated BDL animals, without significant differences in mean arterial pressure. Cirrhotic EPC-treated BDL rats also showed a substantial increase in the hepatic expression of angiogenic receptors, VEGFR2 and CXCR4 in comparison with saline-treated rats.ConclusionThe study suggests that transplantation of cirrhotic EPCs enhances LSEC differentiation and angiogenesis, activates HSCs and worsens fibrosis, thus resulting in hepatic hemodynamic derangements in BDL-induced cirrhosis.

Dataset Information

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

Publications

Comparison of <sup>18</sup>F-FDG, <sup>18</sup>F-Fluoroacetate, and <sup>18</sup>F-FEPPA for Imaging Liver Fibrosis in a Bile Duct-Ligated Rat Model.

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