Non-invasively differentiate non-alcoholic steatohepatitis by visualizing hepatic integrin αvβ3 expression with a targeted molecular imaging modality  

作　　者：Xiao-Quan Huang Ling Wu Chun-Yan Xue Chen-Yi Rao Qing-Qing Fang Ying Chen Cao Xie Sheng-Xiang Rao Shi-Yao Chen Feng Li 

机构地区：[1]Department of Gastroenterology and Hepatology,Zhongshan Hospital,Fudan University,Shanghai 200032,China [2]Department of Gastroenterology,Minhang Hospital,Fudan University,Shanghai 201100,China [3]Department of Pharmacy,Fudan University,Shanghai 200032,China [4]Department of Radiology,Zhongshan Hospital,Fudan University,Shanghai 200032,China

出　　处：《World Journal of Hepatology》2024年第11期1290-1305,共16页世界肝病学杂志（英文）

基　　金：Supported by the National Natural Science Foundation of China,No.81670513;and Young Scientists Fund of the National Natural Science Foundation of China,No.81900511。

摘　　要：BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrin αvβ3-targeted molecular imaging modality to differentiate NASH.METHODS Integrinαvβ3 expression was assessed in Human LO2 hepatocytes Scultured with palmitic and oleic acids(FFA).Hepatic integrinαvβ3 expression was analyzed in rabbits fed a high-fat diet(HFD)and in rats fed a high-fat,high-carbohydrate diet(HFCD).After synthesis,cyclic arginine-glycine-aspartic acid peptide(cRGD)was labeled with gadolinium(Gd)and used as a contrast agent in magnetic resonance imaging(MRI)performed on mice fed with HFCD.RESULTS Integrin αvβ3 was markedly expressed on FFA-cultured hepatocytes,unlike the control hepatocytes.Hepatic integrin αvβ3 expression significantly increased in both HFD-fed rabbits and HFCD-fed rats as simple fatty liver(FL)progressed to steatohepatitis.The distribution of integrinαvβ3 in the liver of NASH cases largely overlapped with albumin-positive staining areas.In comparison to mice with simple FL,the relative liver MRI-T1 signal value at 60 minutes post-injection of Gd-labeled cRGD was significantly increased in mice with steatohepatitis(P<0.05),showing a positive correlation with the NAFLD activity score(r=0.945;P<0.01).Hepatic integrin αvβ3 expression was significantly upregulated during NASH development,with hepatocytes being the primary cells expressing integrin αvβ3.CONCLUSION After using Gd-labeled cRGD as a tracer,NASH was successfully distinguished by visualizing hepatic integrin αvβ3 expression with MRI.

关 键 词：Non-alcoholic steatohepatitis Cyclic peptides Magnetic resonance imaging Non-invasive diagnosis Hepatic integrinαvβ3 

分 类 号：R575.1[医药卫生—消化系统]