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Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments

BACKGROUND: In hepatobiliary imaging, systems detect the total amount of agents originating from extracellular space, bile canaliculi, and hepatocytes. They add in situ concentration of each compartment corrected by its respective volume ratio to provide liver concentrations. In vivo contribution of...

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Autores principales: Pastor, Catherine M., Joly, Florian, Vilgrain, Valérie, Millet, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452805/
https://www.ncbi.nlm.nih.gov/pubmed/34545428
http://dx.doi.org/10.1186/s41747-021-00236-y
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author Pastor, Catherine M.
Joly, Florian
Vilgrain, Valérie
Millet, Philippe
author_facet Pastor, Catherine M.
Joly, Florian
Vilgrain, Valérie
Millet, Philippe
author_sort Pastor, Catherine M.
collection PubMed
description BACKGROUND: In hepatobiliary imaging, systems detect the total amount of agents originating from extracellular space, bile canaliculi, and hepatocytes. They add in situ concentration of each compartment corrected by its respective volume ratio to provide liver concentrations. In vivo contribution of each compartment to liver concentration is inaccessible. Our aim was to quantify the compartmental distribution of two hepatobiliary agents in an ex vivo model and determine how their liver extraction ratios and cholestasis (livers lacking canalicular transporters) might modify it. METHODS: We perfused labelled gadobenate dimeglumine (Bopta, 200 μM, 7% liver extraction ratio) and mebrofenin (Meb, 64 μM, 94% liver extraction ratio) in normal (n = 18) and cholestatic (n = 6) rat livers. We quantified liver concentrations with a gamma counter placed over livers. Concentrations in hepatocytes and bile canaliculi were calculated. Mann-Whitney and Kruskal-Wallis tests were used. RESULTS: Hepatocyte concentrations were 2,043 ± 333 μM (Meb) versus 360 ± 69 μM (Bopta, p < 0.001). Meb extracellular concentrations did not contribute to liver concentrations (1.3 ± 0.3%). The contribution of Bopta extracellular concentration was 12.4 ± 1.9% (p < 0.001 versus Meb). Contribution of canaliculi was similar for both agents (16%). Cholestatic livers had no Bopta in canaliculi but their hepatocyte concentrations increased in comparison to normal livers. CONCLUSION: Hepatocyte concentrations are correlated to liver extraction ratios of hepatobiliary agents. When Bopta is not present in canaliculi of cholestatic livers, hepatocyte concentrations increase in comparison to normal livers. This new understanding extends the interpretation of clinical liver images.
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spelling pubmed-84528052021-10-07 Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments Pastor, Catherine M. Joly, Florian Vilgrain, Valérie Millet, Philippe Eur Radiol Exp Original Article BACKGROUND: In hepatobiliary imaging, systems detect the total amount of agents originating from extracellular space, bile canaliculi, and hepatocytes. They add in situ concentration of each compartment corrected by its respective volume ratio to provide liver concentrations. In vivo contribution of each compartment to liver concentration is inaccessible. Our aim was to quantify the compartmental distribution of two hepatobiliary agents in an ex vivo model and determine how their liver extraction ratios and cholestasis (livers lacking canalicular transporters) might modify it. METHODS: We perfused labelled gadobenate dimeglumine (Bopta, 200 μM, 7% liver extraction ratio) and mebrofenin (Meb, 64 μM, 94% liver extraction ratio) in normal (n = 18) and cholestatic (n = 6) rat livers. We quantified liver concentrations with a gamma counter placed over livers. Concentrations in hepatocytes and bile canaliculi were calculated. Mann-Whitney and Kruskal-Wallis tests were used. RESULTS: Hepatocyte concentrations were 2,043 ± 333 μM (Meb) versus 360 ± 69 μM (Bopta, p < 0.001). Meb extracellular concentrations did not contribute to liver concentrations (1.3 ± 0.3%). The contribution of Bopta extracellular concentration was 12.4 ± 1.9% (p < 0.001 versus Meb). Contribution of canaliculi was similar for both agents (16%). Cholestatic livers had no Bopta in canaliculi but their hepatocyte concentrations increased in comparison to normal livers. CONCLUSION: Hepatocyte concentrations are correlated to liver extraction ratios of hepatobiliary agents. When Bopta is not present in canaliculi of cholestatic livers, hepatocyte concentrations increase in comparison to normal livers. This new understanding extends the interpretation of clinical liver images. Springer International Publishing 2021-09-21 /pmc/articles/PMC8452805/ /pubmed/34545428 http://dx.doi.org/10.1186/s41747-021-00236-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Pastor, Catherine M.
Joly, Florian
Vilgrain, Valérie
Millet, Philippe
Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments
title Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments
title_full Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments
title_fullStr Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments
title_full_unstemmed Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments
title_short Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments
title_sort concentrations and pharmacokinetic parameters of mri and spect hepatobiliary agents in rat liver compartments
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452805/
https://www.ncbi.nlm.nih.gov/pubmed/34545428
http://dx.doi.org/10.1186/s41747-021-00236-y
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