Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs

Abstract Normal liver tissue is highly vulnerable towards irradiation, which remains a challenge in radiotherapy of hepatic tumours. Here, we examined the effects of radiation-induced liver injury on two specific liver functions and hepatocellular regeneration in a minipig model. Five Göttingen mini...

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Autores principales:	Kristoffer Kjærgaard, Britta Weber, Aage Kristian Olsen Alstrup, Jørgen Breede Baltzer Petersen, Rune Hansen, Stephen Jacques Hamilton-Dutoit, Frank Viborg Mortensen, Michael Sørensen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/18ef545d82d04dbbb541ea1279dc0a1e
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spelling	oai:doaj.org-article:18ef545d82d04dbbb541ea1279dc0a1e2021-12-02T16:32:08ZHepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs10.1038/s41598-020-67609-y2045-2322https://doaj.org/article/18ef545d82d04dbbb541ea1279dc0a1e2020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-67609-yhttps://doaj.org/toc/2045-2322Abstract Normal liver tissue is highly vulnerable towards irradiation, which remains a challenge in radiotherapy of hepatic tumours. Here, we examined the effects of radiation-induced liver injury on two specific liver functions and hepatocellular regeneration in a minipig model. Five Göttingen minipigs were exposed to whole-liver stereotactic body radiation therapy (SBRT) in one fraction (14 Gy) and examined 4–5 weeks after; five pigs were used as controls. All pigs underwent in vivo positron emission tomography (PET) studies of the liver using the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine ([11C]CSar) and the galactose-analogue tracer [18F]fluoro-2-deoxy-d-galactose ([18F]FDGal). Liver tissue samples were evaluated histopathologically and by immunohistochemical assessment of hepatocellular mitosis, proliferation and apoptosis. Compared with controls, both the rate constant for secretion of [11C]CSar from hepatocytes into intrahepatic bile ducts as well as back into blood were doubled in irradiated pigs, which resulted in reduced residence time of [11C]CSar inside the hepatocytes. Also, the hepatic systemic clearance of [18F]FDGal in irradiated pigs was slightly increased, and hepatocellular regeneration was increased by a threefold. In conclusion, parenchymal injury and increased regeneration after whole-liver irradiation was associated with enhanced hepatobiliary secretion of bile acids. Whole-liver SBRT in minipigs ultimately represents a potential large animal model of radiation-induced liver injury and for testing of normal tissue protection methods.Kristoffer KjærgaardBritta WeberAage Kristian Olsen AlstrupJørgen Breede Baltzer PetersenRune HansenStephen Jacques Hamilton-DutoitFrank Viborg MortensenMichael SørensenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kristoffer Kjærgaard Britta Weber Aage Kristian Olsen Alstrup Jørgen Breede Baltzer Petersen Rune Hansen Stephen Jacques Hamilton-Dutoit Frank Viborg Mortensen Michael Sørensen Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs
description	Abstract Normal liver tissue is highly vulnerable towards irradiation, which remains a challenge in radiotherapy of hepatic tumours. Here, we examined the effects of radiation-induced liver injury on two specific liver functions and hepatocellular regeneration in a minipig model. Five Göttingen minipigs were exposed to whole-liver stereotactic body radiation therapy (SBRT) in one fraction (14 Gy) and examined 4–5 weeks after; five pigs were used as controls. All pigs underwent in vivo positron emission tomography (PET) studies of the liver using the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine ([11C]CSar) and the galactose-analogue tracer [18F]fluoro-2-deoxy-d-galactose ([18F]FDGal). Liver tissue samples were evaluated histopathologically and by immunohistochemical assessment of hepatocellular mitosis, proliferation and apoptosis. Compared with controls, both the rate constant for secretion of [11C]CSar from hepatocytes into intrahepatic bile ducts as well as back into blood were doubled in irradiated pigs, which resulted in reduced residence time of [11C]CSar inside the hepatocytes. Also, the hepatic systemic clearance of [18F]FDGal in irradiated pigs was slightly increased, and hepatocellular regeneration was increased by a threefold. In conclusion, parenchymal injury and increased regeneration after whole-liver irradiation was associated with enhanced hepatobiliary secretion of bile acids. Whole-liver SBRT in minipigs ultimately represents a potential large animal model of radiation-induced liver injury and for testing of normal tissue protection methods.
format	article
author	Kristoffer Kjærgaard Britta Weber Aage Kristian Olsen Alstrup Jørgen Breede Baltzer Petersen Rune Hansen Stephen Jacques Hamilton-Dutoit Frank Viborg Mortensen Michael Sørensen
author_facet	Kristoffer Kjærgaard Britta Weber Aage Kristian Olsen Alstrup Jørgen Breede Baltzer Petersen Rune Hansen Stephen Jacques Hamilton-Dutoit Frank Viborg Mortensen Michael Sørensen
author_sort	Kristoffer Kjærgaard
title	Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs
title_short	Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs
title_full	Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs
title_fullStr	Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs
title_full_unstemmed	Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs
title_sort	hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by pet in göttingen minipigs
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/18ef545d82d04dbbb541ea1279dc0a1e
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Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in Göttingen minipigs

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