TY - JOUR
T1 - Complete elimination of the hepatobiliary mr contrast agent Gd-EOB-DTPA in hepatic dysfunction
T2 - An experimental study using transport-deficient, mutant rats
AU - Muhler, Andreas
AU - Oude Elferink, Ronald P.J.
AU - Weinmann, Hanns Joachim
PY - 1993/9
Y1 - 1993/9
N2 - Mutant Wistar rats (TR- rats) are characterized by a defect in the canalicular transport system for organic anions in the hepatocytes. Anionic hepatobiliary contrast agents for X-ray and MR imaging usually depend on this transport system for biliary secretion. The current study investigated in rats whether Gd-EOB-DTPA, a hepatocyte-directed MR contrast agent, can be completely eliminated in the absence of biliary excretion, and whether urinary elimination may compensate for the hepatic dysfunction. In TR/t- rats elimination of Gd-EOB-DTPA almost completely depended on renal excretion: following intravenous administration of 25 μmol kg-1 Gd-EOB-DTPA only 2.4±0.4% of the injected dose underwent biliary excretion. Nevertheless only 2% of a 10-fold higher dose (250 μmolkg-1 Gd-EOB-DTPA) was still detected in the body 24 hours p.a., and less than 0.5% 7 days p.a. (no statistically significant differences as compared to values in control rats). In TR- rats, renal and liver signal intensities on T1-weighted MR images returned to baseline within 24 hours following administration of 25 μmol kg-1 Gd-EOB-DTPA. In control rats, return to baseline values was observed already 6 hours after injection of the contrast agent. In conclusion, the hepatobiliary MR contrast agent Gd-EOB-DTPA is effectively and completely cleared from the body even in the virtual absence of biliary excretion. The urinary elimination pathway is able to fully compensate for the deficient hepatic transport system.
AB - Mutant Wistar rats (TR- rats) are characterized by a defect in the canalicular transport system for organic anions in the hepatocytes. Anionic hepatobiliary contrast agents for X-ray and MR imaging usually depend on this transport system for biliary secretion. The current study investigated in rats whether Gd-EOB-DTPA, a hepatocyte-directed MR contrast agent, can be completely eliminated in the absence of biliary excretion, and whether urinary elimination may compensate for the hepatic dysfunction. In TR/t- rats elimination of Gd-EOB-DTPA almost completely depended on renal excretion: following intravenous administration of 25 μmol kg-1 Gd-EOB-DTPA only 2.4±0.4% of the injected dose underwent biliary excretion. Nevertheless only 2% of a 10-fold higher dose (250 μmolkg-1 Gd-EOB-DTPA) was still detected in the body 24 hours p.a., and less than 0.5% 7 days p.a. (no statistically significant differences as compared to values in control rats). In TR- rats, renal and liver signal intensities on T1-weighted MR images returned to baseline within 24 hours following administration of 25 μmol kg-1 Gd-EOB-DTPA. In control rats, return to baseline values was observed already 6 hours after injection of the contrast agent. In conclusion, the hepatobiliary MR contrast agent Gd-EOB-DTPA is effectively and completely cleared from the body even in the virtual absence of biliary excretion. The urinary elimination pathway is able to fully compensate for the deficient hepatic transport system.
KW - contrast agent
KW - elimination
KW - gadolinium
KW - liver
KW - mr contrast agent
KW - transport systems
UR - http://www.scopus.com/inward/record.url?scp=0006419795&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/BF01769415
DO - https://doi.org/10.1007/BF01769415
M3 - Article
SN - 0968-5243
VL - 1
SP - 134
EP - 139
JO - MAGMA Magnetic Resonance Materials in Physics, Biology, and Medicine
JF - MAGMA Magnetic Resonance Materials in Physics, Biology, and Medicine
IS - 3-4
ER -