HEPATIC KINETICS AND MAGNETIC-RESONANCE-IMAGING OF GADOLINIUM-EOB-DTPA IN DOGS

RATIONALE AND OBJECTIVES. TO measure the hepatic uptake and biliary el imination kinetics of gadolinium (Gd)-EOB-DTPA in dogs. METHOD. TWO gr oups of four beagles each were anesthetized and given an intravenous b olus of 25 mu mol/kg or 250 mu mol/kg of Gd-EOB-DTPA. Blood, hepatic b ile, and urine were collected over 140 minutes, and liver samples were obtained immediately after the dogs were killed, Conventional T1-weig hted spin echo sequences of the liver were performed on a 1.5-Tesla (T ) magnetic resonance imager during sampling. A ninth beagle received a bolus of 25 mu mol/kg followed 140 minutes later with a bolus of 250 mu mol/kg of Gd-EOB-DTPA. Wedge liver biopsies were obtained for Gd es timation at various times after dosing, and Gd concentration was measu red by inductively coupled plasma atomic emission spectroscopy. RESULT S. The plasma concentration of Gd-EOB-DTPA decreased in a biexponentia l manner with half-lives of approximately 4 minutes and 60 minutes for the distribution and elimination phase independent of the dose given, Gadolinium bile concentration reached peak values between 80 and 140 minutes: 6.3 +/- 1.6 mmol/L for the low dose (LD) and 11.6 +/- 2.8 mmo l/L for the high dose (HD). Bile Gd output was 62.0 +/- 8.8 (LD) and 7 8.3 +/- 30.2 (HD) nmol/minute kg 50 to 80 minutes after injection. Gad olinium-EOB-DTPA was excreted by the biliary route to 24.8 +/- 2.6 (LD ) and 3.6 +/- 1.2 (HD) percent of the dose within 140 minutes. Liver G d concentration was 0.43 +/- 0.14 (LD) and 4.3 +/- 0.5 (HD) mmol/kg li ver tissue at the conclusion of the studies, Calculated concentrations in the hepatocyte were 60 (LD) and 15 (HD) times higher than in plasm a at 25 minutes after dosing, Whereas the low dose exhibited excellent contrast enhancement for the whole period, the high dose displayed a biphasic signal enhancement with a decreasing signal caused by the too -high hepatic gadolinium accumulation. CONCLUSIONS. Transport of the G d-EOB-DTPA into the hepatocyte exceeded elimination from hepatocyte to bile. The high dose defined a biliary transport maximum for Gd-EOB-DT PA of 78.3 +/- 30.2 nmol/minute . kg. The liver accumulation results f rom fast transport into the hepatocyte and rate-limited slower transpo rt from hepatocyte to bile. The accumulation occurs against a strong c oncentration gradient, suggesting energy-dependent active transport in to the hepatocyte.