Document Detail


Concentrations of Gd-BOPTA in cholestatic fatty rat livers: role of transport functions through membrane proteins.
MedLine Citation:
PMID:  23281287     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Gd-BOPTA (gadobenate dimeglumine) is a magnetic resonance (MR) contrast agent that, after i.v. administration, distributes within the extracellular space, enters rat hepatocytes through the sinusoidal transporters organic anion transporting peptides (Oatps) and is excreted unchanged into bile through the multidrug resistance-associated protein 2 (Mrp2). It is unclear how the hepatobiliary contrast agent would accumulate in cholestatic fatty livers from obese rats with bile flow impairment. Indeed, the expression of both Oatps and Mrp2 transporters is decreased in cholestatic hepatocytes. To assess this question, we measured on-line the hepatic concentrations of (153) Gd-BOPTA with a gamma probe placed over perfused rat livers. During the perfusion of (153) Gd-BOPTA, we obtained a similar maximal hepatic concentration in normal and fatty livers despite the decreased expression and function of membrane transporters in fatty livers. By pharmacokinetic modeling and mathematical simulations, we show how changes of transport into and out of hepatocytes modify the concentrations of (153) Gd-BOPTA within hepatocytes. Mathematical simulations help to understand how each parameter (entry into hepatocytes, bile excretion, or efflux back to sinusoids) interferes with the hepatic concentrations. The hepatic concentrations of (153) Gd-BOPTA within hepatocytes rely on the entry into hepatocytes through the sinusoidal membrane and on two paths of exit, the efflux back to sinusoids and the elimination into bile. Understanding how (153) Gd-BOPTA accumulates in hepatocytes is then complex. However, such understanding is important to analyze liver imaging with hepatobiliary contrast agents in cholestatic fatty livers. Copyright © 2012 John Wiley & Sons, Ltd.
Authors:
Catherine M Pastor; Michael Wissmeyer; Philippe Millet
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Contrast media & molecular imaging     Volume:  8     ISSN:  1555-4317     ISO Abbreviation:  Contrast Media Mol Imaging     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101286760     Medline TA:  Contrast Media Mol Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  147-56     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
Affiliation:
Laboratoire de Physiopathologie Hépatique et Imagerie Moléculaire.
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