Background Safety concerns caused by
gadolinium retention call for the development of high-relaxivity
gadolinium-based
contrast agents (GBCAs) allowing minimal dosing. Purpose To investigate brain
gadolinium retention in healthy rats after exposure to
gadopiclenol (Elucirem, Guerbet; macrocyclic GBCA) compared with
gadobutrol (
Gadovist or Gadavist, Bayer; macrocyclic GBCA) and
gadodiamide (
Omniscan, GE Healthcare; linear GBCA) over 1 year. Materials and Methods In this study conducted between May 2018 and April 2020, 9-week-old healthy Sprague Dawley rats received five
injections of either
gadopiclenol,
gadobutrol, or
gadodiamide (2.4 mmol of
gadolinium per kilogram of
body weight for each), or saline (control animals) over a period of 5 weeks. Rats were randomly assigned to different groups (six female and six male rats per group). MRI examinations were performed before
euthanasia at 1, 3, 5, or 12 months after the last injection. Brains were sampled to determine the total
gadolinium content via inductively coupled plasma mass spectrometry (ICP-MS), to characterize
gadolinium species with size exclusion chromatography (SEC)-ICP-MS, and to perform elemental mapping with
laser ablation (LA)-ICP-MS. Mann-Whitney tests were performed on pairwise comparisons of the same time points. Results For both macrocyclic agents, no T1 signal hyperintensities were observed in the cerebellum, and approximately 80% of
gadolinium washout was found between 1 month (
gadobutrol, 0.30 nmol/g;
gadopiclenol, 0.37 nmol/g) and 12 months (
gadobutrol, 0.062 nmol/g;
gadopiclenol, 0.078 nmol/g). After 12 months, only low-molecular-weight
gadolinium species were detected in the soluble fraction.
Gadodiamide led to significantly higher
gadolinium concentrations after 1 month in the cerebellum (
gadodiamide, 2.65 nmol/g; P < .001 vs both macrocyclics) combined with only 15% washout after 12 months (
gadodiamide, 2.25 nmol/g) and with
gadolinium detected bound to macromolecules. Elemental bioimaging enabled visualization of
gadolinium deposition patterns colocalized with
iron. Conclusion
Gadopiclenol and
gadobutrol demonstrated similar in vivo distribution and washout of
gadolinium in the healthy rat brain, markedly differing from
gadodiamide up to 12 months after the last injection. © RSNA, 2022 Online supplemental material is available for this article.