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Utility of Translocator Protein (18 kDa) as a Molecular Imaging Biomarker to Monitor the Progression of Liver Fibrosis

Hepatic fibrosis is the wound healing response to chronic hepatic injury caused by various factors. In this study, we aimed to evaluate the utility of translocator protein (18 kDa) (TSPO) as a molecular imaging biomarker for monitoring the progression of hepatic fibrosis to cirrhosis. Model rats wer...

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Autores principales: Hatori, Akiko, Yui, Joji, Xie, Lin, Kumata, Katsushi, Yamasaki, Tomoteru, Fujinaga, Masayuki, Wakizaka, Hidekatsu, Ogawa, Masanao, Nengaki, Nobuki, Kawamura, Kazunori, Wang, Feng, Zhang, Ming-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661446/
https://www.ncbi.nlm.nih.gov/pubmed/26612465
http://dx.doi.org/10.1038/srep17327
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author Hatori, Akiko
Yui, Joji
Xie, Lin
Kumata, Katsushi
Yamasaki, Tomoteru
Fujinaga, Masayuki
Wakizaka, Hidekatsu
Ogawa, Masanao
Nengaki, Nobuki
Kawamura, Kazunori
Wang, Feng
Zhang, Ming-Rong
author_facet Hatori, Akiko
Yui, Joji
Xie, Lin
Kumata, Katsushi
Yamasaki, Tomoteru
Fujinaga, Masayuki
Wakizaka, Hidekatsu
Ogawa, Masanao
Nengaki, Nobuki
Kawamura, Kazunori
Wang, Feng
Zhang, Ming-Rong
author_sort Hatori, Akiko
collection PubMed
description Hepatic fibrosis is the wound healing response to chronic hepatic injury caused by various factors. In this study, we aimed to evaluate the utility of translocator protein (18 kDa) (TSPO) as a molecular imaging biomarker for monitoring the progression of hepatic fibrosis to cirrhosis. Model rats were induced by carbon tetrachloride (CCl(4)), and liver fibrosis was assessed. Positron emission tomography (PET) with N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[(18)F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]-acetamide ([(18)F]FEDAC), a radioprobe specific for TSPO, was used for noninvasive visualisation in vivo. PET scanning, immunohistochemical staining, ex vivo autoradiography, and quantitative reverse-transcription polymerase chain reaction were performed to elucidate the relationships among radioactivity uptake, TSPO levels, and cellular sources enriching TSPO expression in damaged livers. PET showed that uptake of radioactivity in livers increased significantly after 2, 4, 6, and 8 weeks of CCl(4) treatment. Immunohistochemistry demonstrated that TSPO was mainly expressed in macrophages and hepatic stellate cells (HSCs). TSPO-expressing macrophages and HSCs increased with the progression of liver fibrosis. Interestingly, the distribution of radioactivity from [(18)F]FEDAC was well correlated with TSPO expression, and TSPO mRNA levels increased with the severity of liver damage. TSPO was a useful molecular imaging biomarker and could be used to track the progression of hepatic fibrosis to cirrhosis with PET.
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spelling pubmed-46614462015-12-02 Utility of Translocator Protein (18 kDa) as a Molecular Imaging Biomarker to Monitor the Progression of Liver Fibrosis Hatori, Akiko Yui, Joji Xie, Lin Kumata, Katsushi Yamasaki, Tomoteru Fujinaga, Masayuki Wakizaka, Hidekatsu Ogawa, Masanao Nengaki, Nobuki Kawamura, Kazunori Wang, Feng Zhang, Ming-Rong Sci Rep Article Hepatic fibrosis is the wound healing response to chronic hepatic injury caused by various factors. In this study, we aimed to evaluate the utility of translocator protein (18 kDa) (TSPO) as a molecular imaging biomarker for monitoring the progression of hepatic fibrosis to cirrhosis. Model rats were induced by carbon tetrachloride (CCl(4)), and liver fibrosis was assessed. Positron emission tomography (PET) with N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[(18)F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]-acetamide ([(18)F]FEDAC), a radioprobe specific for TSPO, was used for noninvasive visualisation in vivo. PET scanning, immunohistochemical staining, ex vivo autoradiography, and quantitative reverse-transcription polymerase chain reaction were performed to elucidate the relationships among radioactivity uptake, TSPO levels, and cellular sources enriching TSPO expression in damaged livers. PET showed that uptake of radioactivity in livers increased significantly after 2, 4, 6, and 8 weeks of CCl(4) treatment. Immunohistochemistry demonstrated that TSPO was mainly expressed in macrophages and hepatic stellate cells (HSCs). TSPO-expressing macrophages and HSCs increased with the progression of liver fibrosis. Interestingly, the distribution of radioactivity from [(18)F]FEDAC was well correlated with TSPO expression, and TSPO mRNA levels increased with the severity of liver damage. TSPO was a useful molecular imaging biomarker and could be used to track the progression of hepatic fibrosis to cirrhosis with PET. Nature Publishing Group 2015-11-27 /pmc/articles/PMC4661446/ /pubmed/26612465 http://dx.doi.org/10.1038/srep17327 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Hatori, Akiko
Yui, Joji
Xie, Lin
Kumata, Katsushi
Yamasaki, Tomoteru
Fujinaga, Masayuki
Wakizaka, Hidekatsu
Ogawa, Masanao
Nengaki, Nobuki
Kawamura, Kazunori
Wang, Feng
Zhang, Ming-Rong
Utility of Translocator Protein (18 kDa) as a Molecular Imaging Biomarker to Monitor the Progression of Liver Fibrosis
title Utility of Translocator Protein (18 kDa) as a Molecular Imaging Biomarker to Monitor the Progression of Liver Fibrosis
title_full Utility of Translocator Protein (18 kDa) as a Molecular Imaging Biomarker to Monitor the Progression of Liver Fibrosis
title_fullStr Utility of Translocator Protein (18 kDa) as a Molecular Imaging Biomarker to Monitor the Progression of Liver Fibrosis
title_full_unstemmed Utility of Translocator Protein (18 kDa) as a Molecular Imaging Biomarker to Monitor the Progression of Liver Fibrosis
title_short Utility of Translocator Protein (18 kDa) as a Molecular Imaging Biomarker to Monitor the Progression of Liver Fibrosis
title_sort utility of translocator protein (18 kda) as a molecular imaging biomarker to monitor the progression of liver fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661446/
https://www.ncbi.nlm.nih.gov/pubmed/26612465
http://dx.doi.org/10.1038/srep17327
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