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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.

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