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 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.

Long-Term Clinical Investigation of the Hepatobiliary Agents: 99mTc- HIDA and 99mTC-p-Butyl-IDA

The organ distribution data for the two hepatobiliary agents HIDA and p-butyl- IDA in mice showed substantial differences in the extent and rate of hepatobiliary clearance of radioactivity. 99mTc-HIDA and 99mTc-p-butyl-IDA were used in computer assisted serial hepatobiliary scintigraphy. In normal subjects, the data of dynamic studies showed that the kidneys were no longer seen after 2.5 min with p-butyl-IDA. Liver radioactivity decreased significantly after 10 min with HIDA compared to 35 min with p-butyl-IDA. The gall bladder was always visualized at the 10-12th min and the 25-30th min with HIDA and p-butyl-IDA respectively. 99mTc-HIDA provided superior hepatic duct images.