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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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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 3-fold. 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.
Translated title of the contributionHepatisk regeneration som følge af stråleinduceret leverskade er associeret med øget hepatobiliær sekretion målt med PET i Göttingen minigrise
Original languageEnglish
Article number10858
JournalScientific Reports
Number of pages10
Publication statusPublished - 2 Jul 2020

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