Gadolinium Retention and Clearance in the Diabetic Brain after Administrations of Gadodiamide, Gadopentetate Dimeglumine, and Gadoterate Meglumine in a Rat Model

PURPOSE: To evaluate gadolinium (Gd) retention and clearance in the brain of diabetic rats after administrations of gadodiamide, gadopentetate dimeglumine, and gadoterate meglumine. MATERIALS AND METHODS: Both diabetic rats (n = 52) and normal rats (n = 52) intravenously received 20 injections of 0.6 mmol Gd/kg gadodiamide, gadopentetate dimeglumine, gadoterate meglumine, or saline. Both diabetic rats and normal rats were divided into 2 subgroups of 24 and 28 rats for the 7-day and 42-day evaluations (i.e., they were sacrificed at 7 days (n = 6 per group) and 42 days (n = 7 per group)), respectively, after the last injection. For the 7-day subgroup, 6 rats were euthanized for inductively coupled plasma mass spectrometry (ICP-MS) analysis. For the 42-day subgroup, 6 rats underwent T1-weighted magnetic resonance imaging (MRI) and ICP-MS, and 1 rat was analyzed by transmission electron microscopy (TEM). RESULTS: The T1 enhancements in the deep cerebellar nuclei (DCNs) of diabetic rats were lower than those of normal rats in both linear Gd-based contrast agent (GBCA) groups (p < 0.05). The average Gd concentrations in the brains of diabetic rats were significantly lower than those of healthy rats in both the short-term groups and long-term groups (p < 0.05). The highest Gd retentions were in the olfactory bulb, DCN, and striatum with gadodiamide. Compared with the results obtained 7 days after the last injection, the residual Gd concentrations of the 42-day subgroups in the brains of diabetic rats showed no significant difference in both linear GBCA groups (p>0.05). CONCLUSIONS: Compared with normal rats, the diabetic status decreased the residual Gd concentrations in the brain after multiple administrations of gadodiamide, gadopentetate dimeglumine, and gadoterate meglumine. The clearable fraction of Gd in the brain was eliminated faster in diabetic rats than in normal rats.