Gadolinium Clearance in the First 5 Weeks After Repeated Intravenous Administration of Gadoteridol, Gadoterate Meglumine, and Gadobutrol to rats

Abstract

Background: Studies of gadolinium (Gd) clearance from animals in the first weeks after administration of gadolinium-based contrast agents (GBCAs) have previously looked at solitary timepoints only. However, this does not give information on differences between GBCAs and between organs in terms of Gd elimination kinetics.

Purpose: To compare Gd levels in rat cerebellum, cerebrum, skin, and blood at 1, 2, 3, and 5 weeks after repeated administration of macrocyclic GBCAs.

Study type: Prospective.

Animal model: One hundred eighty male Sprague-Dawley rats randomized to three groups (n = 60/group), received intravenous administrations of gadoteridol, gadoterate meglumine, or gadobutrol (0.6 mmol/kg for each) four times/week for 5 consecutive weeks. Rats were sacrificed after washout periods of 1, 2, 3, or 5 weeks.

Field strength/sequence: Not applicable.

Assessment: Cerebellum, cerebrum, skin, and blood were harvested for Gd determination by inductively coupled plasma-mass spectrometry (15 animals/group/all timepoints).

Statistical tests: Anova and Dunnett's test (data with homogeneous variances and normal distribution). Kruskal-Wallis and Wilcoxon's rank sum tests (data showing nonhomogeneous variances or a non-normal distribution, significance levels: P < 0.05, P < 0.01, and P < 0.001).

Results: Gd levels in cerebellum, cerebrum, and skin were significantly lower after gadoteridol than after gadoterate and gadobutrol at all timepoints. Mean cerebellum Gd concentrations after gadoteridol, gadoterate, and gadobutrol decreased from 0.693, 0.878, and 1.011 nmol Gd/g at 1 week to 0.144, 0.282, and 0.297 nmol Gd/g at 5 weeks after injection. Similar findings were noted for cerebrum and skin. Conversely, significantly higher Gd levels were noted in blood after gadoteridol compared to gadobutrol at 1, 2, and 3 weeks and compared to gadoterate at all timepoints.

Data conclusion: Gadoteridol is eliminated more rapidly from rat cerebellum, cerebrum, and skin compared to gadoterate and gadobutrol in the first 5 weeks after administration, resulting in lower levels of retained Gd in these tissues.

Evidence level: 1 TECHNICAL EFFICACY: Stage 5.

Keywords: GBCA; gadobutrol; gadolinium retention; gadoterate; gadoteridol; rats.