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[18F]- Alfatide PET imaging of integrin αvβ3 for the non-invasive quantification of liver fibrosis.

Authors
  • Shao, Tuo1
  • Chen, Zhen2
  • Belov, Vasily3
  • Wang, Xiaohong4
  • Rwema, Steve H5
  • Kumar, Viksit4
  • Fu, Hualong2
  • Deng, Xiaoyun2
  • Rong, Jian2
  • Yu, Qingzhen2
  • Lang, Lixin6
  • Lin, Wenyu5
  • Josephson, Lee2
  • Samir, Anthony E4
  • Chen, Xiaoyuan7
  • Chung, Raymond T8
  • Liang, Steven H9
  • 1 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology; Liver Center and Gastrointestinal Division, Department of Medicine.
  • 2 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology.
  • 3 Massachusetts General Hospital, Shriners Hospitals for Children, Boston, USA.
  • 4 Center for Ultrasound Research & Translation, Department of Radiology, Massachusetts General Hospital, Boston, USA.
  • 5 Liver Center and Gastrointestinal Division, Department of Medicine.
  • 6 Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, USA.
  • 7 Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, USA. Electronic address: [email protected]
  • 8 Liver Center and Gastrointestinal Division, Department of Medicine. Electronic address: [email protected]
  • 9 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology. Electronic address: [email protected]
Type
Published Article
Journal
Journal of hepatology
Publication Date
Mar 04, 2020
Identifiers
DOI: 10.1016/j.jhep.2020.02.018
PMID: 32145257
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The vitronectin receptor integrin alpha v beta 3 (αvβ3) drives fibrogenic activation of hepatic stellate cells (HSC). Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on activated HSCs (aHSCs) in the injured liver. In this study, we sought to compare differences in uptake of the [18F]-Alfatide between normal and injured liver to evaluate its utility for assessment of hepatic fibrogenesis. PET with [18F]-Alfatide, non-enhanced computerized tomography (CT), histopathology, immunofluorescence staining, immunoblotting and gene analysis were performed to evaluate and quantify hepatic integrin αvβ3 levels and liver fibrosis progression in carbon-tetrachloride (CCl4) and bile duct ligation (BDL) induced liver fibrosis mice model. The AUC liver 0-30 min to AUC blood 0-30 min contrast was used as an integrin αvβ3-PET index to quantify fibrosis progression. Ex vivo analysis of frozen liver tissue from patients with fibrosis and cirrhosis verified the animal findings. Fibrotic mouse livers showed enhanced [18F]-Alfatide uptake and retention compared to control livers. The radiotracer was demonstrated to bind specifically with integrin αvβ3 mainly expressed on aHSCs. Autoradiography and histopathology confirmed the PET imaging results. Further, the mRNA and protein level of integrin αvβ3 and its signaling complex were higher in CCl4 and BDL models compared to controls. Human fibrotic liver section results supported the animal findings. Imaging hepatic integrin αvβ3 with PET and [18F]-Alfatide offers a potential noninvasive method for monitoring the progression of liver fibrosis. Copyright © 2020. Published by Elsevier B.V.

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