Hepatic kinetics and magnetic resonance imaging of gadolinium-EOB-DTPA in dogs.

RATIONALE AND OBJECTIVES: To measure the hepatic uptake and biliary elimination kinetics of gadolinium (Gd)-EOB-DTPA in dogs. METHOD: Two groups of four beagles each were anesthetized and given an intravenous bolus of 25 mumol/kg or 250 mumol/kg of Gd-EOB-DTPA. Blood, hepatic bile, and urine were collected over 140 minutes, and liver samples were obtained immediately after the dogs were killed. Conventional T1-weighted 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 mumol/kg followed 140 minutes later with a bolus of 250 mumol/kg of Gd-EOB-DTPA. Wedge liver biopsies were obtained for Gd estimation at various times after dosing, and Gd concentration was measured by inductively coupled plasma atomic emission spectroscopy. RESULTS: The plasma concentration of Gd-EOB-DTPA decreased in a biexponential 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 +/- mmol/L for the high dose (HD). Bile Gd output was 62.0 +/- 8.8 (LD) and 78.3 +/- 30.2 (HD) nmol/minute-kg 50 to 80 minutes after injection. Gadolinium-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 Gd concentration was 0.43 +/- 0.14 (LD) and 4.3 +/- 0.5 (HD) mmol/kg liver tissue at the conclusion of the studies. Calculated concentrations in the hepatocyte were 60 (LD) and 15 (HD) times higher than in plasma 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 Gd-EOB-DTPA into the hepatocyte exceeded elimination from hepatocyte to bile. The high dose defined a biliary transport maximum for Gd-EOB-DTPA of 78.3 +/- 30.2 nmol/minute-kg. The liver accumulation results from fast transport into the hepatocyte and rate-limited slower transport from hepatocyte to bile. The accumulation occurs against a strong concentration gradient, suggesting energy-dependent active transport into the hepatocyte.

Hepatic kinetics and magnetic resonance imaging of gadolinium ethoxybenzyl diethylenetriaminepentacetic acid (Gd-EOB-DTPA) in dogs.

This complex study was designed to measure the transport and excretion characteristics of gadolinium ethoxybenzyl diethylenetriaminepentacetic acid (Gd-EOB-DTPA) in dog's livers following bolus and infusion. Simultaneous T1 magnetic resonance imaging was performed to measure maximum signal enhancement. Anaesthetized dogs had cannulation of the common bile duct and urinary bladder for collections and cannulation of the femoral artery and vein for monitoring, blood sampling and infusion. Gd-EOB-DTPA was administered by bolus (range 12.5-200 mumol/kg) and infusion (range 0.4-6.4 mumol/min per kg). An hepatic transport maximum 0.09-0.15 mumol/min/kg was achieved with a blood concentration of 0.03-0.06 mumol/mL. Marked hepatic affinity for Gd-EOB-DTPA was demonstrated with measurements of liver concentration. Maximum T1 signal enhancement was achieved with blood Gd-EOB-DTPA concentration of 0.02-0.03 mumol/mL and a liver concentration of 1-2 mumol/g. The transport maximum for Gd-EOB-DTPA in the dog was similar to that for ipodate and iodipamide and effective imaging was achieved with sub-maximal doses. The maximum signal enhancement at blood concentrations less than required for maximum transport suggest a wide latitude for effective clinical imaging.

Costs of magnetic resonance imaging services in public hospitals.

Audited cost data from two public hospital installations participating in a trial of the utilisation and efficacy of magnetic resonance imaging are presented. The data cover the period July 1987 to June 1988 when both installations had attained stable patterns of operation. One hospital operated a superconductive system and the other a resistive magnetic resonance imaging unit. Depreciation and salaries represented the major components of cost.

Influence of contrast media osmolality on intravenous urographic quality.

A clinical study was designed to determine whether the lower solute load after intravenous injection of nonionic contrast medium (CM) produced significant changes in nephrographic and pyelographic quality. For equal iodine doses (300 mg I/kg), the lower solute load of nonionic CM produced better nephrogram and pyelogram scores than ionic CM or nonionic CM with mannitol, both of which had higher solute loads. The higher scores associated with nonionic CM were statistically significant for the pyelogram phase but not for the nephrogram phase. These observations were matched by lesser changes in urinary osmolality and higher urinary iodine concentrations with the nonionic CM.

Renal excretion and computed tomography enhancement of iotrolan and iopamidol in dogs.

A comparison of the renal excretion and computed tomography (CT) enhancement of nonionic, monomer and dimer contrast media (CM) (iopamidol and iotrolan) was planned to determine if the latter provides additional and prolonged enhancement in dogs. The excretion studies show almost identical performance of both CM with respect to plasma concentration and renal excretion. However, the lower osmolality of iotrolan permits greater renal concentration in the medulla, papilla, and urine. The potential for this further enhancement of the kidney in CT or urography is marginal.

Ethical and financial considerations in Australia.

Australian nonionic contrast media experience follows the European pattern and anticipates developments in the United States. Cost concerns and unclear safety advantages led the Royal Australian College of Radiologists to develop guidelines for contrast media usage and an adverse reaction survey.

Examination of the nephrographic potential of iotrol by computed tomography.

The x-ray attenuation of the renal cortex of dogs, as determined by computed tomographic (CT) scanning, was measured over a three-day period after an intravenous bolus of 600 mg I/kg of iotrol or iopamidol. A slightly higher density observed 24 hours after injection of iotrol was not considered significant, and was not considered sufficient to warrant clinical application of iotrol for specific, prolonged renal enhancement.

Comparison of blood-brain barrier disruption by intracarotid iopamidol and methylglucamine iothalamate.

Using a canine model, the effect of intracarotid injections of the ionic contrast medium methylglucamine iothalamate was compared with that of the nonionic contrast medium iopamidol of similar iodine concentration (280 mg 1/ml). The degree and distribution of blood-brain barrier disruption was assessed using Evans blue stain as a visual marker and by contrast enhancement measured by a computed tomographic (CT) scanner. In all studies with methylglucamine iothalamate, Evans blue staining was demonstrated, and CT enhancement demonstrated a significant mean difference (p less than 0.01) between the control and injected hemispheres. The absence of blood-brain barrier disruption with iopamidol is probably related to its lower osmolality (570 mosmol/kg) compared with methylglucamine iothalamate (1,424 mosmol/kg) and the absence of any cation.