Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments
Abstract 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 contrib...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2021-09-01
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| Series: | European Radiology Experimental |
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| Online Access: | https://doi.org/10.1186/s41747-021-00236-y |
| _version_ | 1818622956575653888 |
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| author | Catherine M. Pastor Florian Joly Valérie Vilgrain Philippe Millet |
| author_facet | Catherine M. Pastor Florian Joly Valérie Vilgrain Philippe Millet |
| author_sort | Catherine M. Pastor |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-16T18:33:24Z |
| format | Article |
| id | doaj.art-96f0a710f87d4cb99294a117653ce265 |
| institution | Directory Open Access Journal |
| issn | 2509-9280 |
| language | English |
| last_indexed | 2024-12-16T18:33:24Z |
| publishDate | 2021-09-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | European Radiology Experimental |
| spelling | doaj.art-96f0a710f87d4cb99294a117653ce2652022-12-21T22:21:14ZengSpringerOpenEuropean Radiology Experimental2509-92802021-09-015111010.1186/s41747-021-00236-yConcentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartmentsCatherine M. Pastor0Florian Joly1Valérie Vilgrain2Philippe Millet3Centre de recherche sur l’inflammation, Inserm, U1149, CNRS, ERL8252, Université de ParisCentre de recherche sur l’inflammation, Inserm, U1149, CNRS, ERL8252, Université de ParisCentre de recherche sur l’inflammation, Inserm, U1149, CNRS, ERL8252, Université de ParisDepartment of Psychiatry, University Hospital of GenevaAbstract 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.https://doi.org/10.1186/s41747-021-00236-yMembrane transport proteinsCholestasisHepatocytesBile canaliculiExtracellular space |
| spellingShingle | Catherine M. Pastor Florian Joly Valérie Vilgrain Philippe Millet Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments European Radiology Experimental Membrane transport proteins Cholestasis Hepatocytes Bile canaliculi Extracellular space |
| 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 | Membrane transport proteins Cholestasis Hepatocytes Bile canaliculi Extracellular space |
| url | https://doi.org/10.1186/s41747-021-00236-y |
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