The Macrocyclic Gadolinium-Based Contrast Agents Gadobutrol and Gadoteridol Show Similar Elimination Kinetics From the Brain After Repeated Intravenous Injections in Rabbits.

MATERIALS AND METHODS

Male white New Zealand rabbits (2.4-3.1 kg) in 2 study groups (n = 21 each) received 3 injections of either gadobutrol or gadoteridol at 0.9 mmol Gd/kg within 5 days (total dose, 2.7 mmol Gd/kg). Animals in one control group (n = 9) received 3 injections of saline (1.8 mL/kg). After 2, 6, and 12 weeks, 7 animals from each study group and 3 from the control group were killed and the Gd concentrations in the cerebellum, cerebrum, in blood and in urine were determined by inductively coupled plasma mass spectrometry. The chemical species of excreted Gd in urine were determined by high pressure liquid chromatography.

RESULTS

No significant (P > 0.05) differences in the Gd concentrations in the brain of rabbits were observed between the 2 macrocyclic GBCAs gadoteridol and gadobutrol at all time points. In the gadobutrol group, the mean Gd concentrations in the cerebellum and cerebrum decreased from 0.26 and 0.21 nmol Gd/g after 2 weeks, to 0.040 and 0.027 nmol Gd/g after 12 weeks, respectively, and in the gadoteridol group, from 0.25 and 0.21, to 0.037 and 0.023 nmol Gd/g, respectively. The plasma levels decreased from 0.11 and 0.13 nmol Gd/mL at 2 weeks for gadobutrol and gadoteridol to below the limit of quantification (<0.005 nmol Gd/mL) at 12 weeks. The urine concentration dropped in a biphasic course from 2 to 6 and from 6 to 12 weeks for both agents. The Gd excreted after 12 weeks was still present in the urine in the chemical form of the intact Gd complex for both agents.

CONCLUSIONS

Contrary to what had been reported in rats, no significant differences in the elimination kinetics from brain tissue in rabbits were observed after intravenous injection of multiple doses of the macrocyclic GBCAs gadobutrol and gadoteridol.