Short- and Long-Term Effects of a Single Exposure to Gadoteric Acid in Healthy Rats-Gadolinium, Iron and Other Metal Accumulation in Kidney and Brain.

Gadolinium [Gd (III)] released from gadolinium-based contrast agents, commonly used in magnetic resonance imaging, may accumulate in organs, altering metal homeostasis. We aimed to clarify Gd (III), iron and other metal accumulation in the kidney and brain, in the short (2 days) and long term (20 weeks), following exposure to gadoteric acid (Gd-DOTA) or free Gd (III). Wistar rats received one dose of Gd (III), Gd-DOTA, or saline. Gd (III) and metal levels in the blood (whole blood, and serum in the case of iron), kidney, and brain, and iron metabolism biomarkers, were assessed. Gd (III) was detectable in the blood, kidney, and brain, at both time points, for both Gd (III) and Gd-DOTA-treated groups. Exposure to free Gd (III) showed a significant Gd (III) accumulation in the kidney, brain and blood in the short term and long term; Gd-DOTA presented significant accumulation only in the short term. Gd-DOTA appears to have faster elimination and minimal brain deposition. Exposure to free Gd (III), but not to Gd-DOTA, led to disturbances in metal homeostasis and in iron metabolism markers (serum ferritin and transferrin saturation), but did not alter tissue iron levels. In summary, the kidney appears as the primary site of accumulation and retention. Despite the safer profile shown by Gd-DOTA in the long term, our data highlight the importance of clarifying the pathophysiological implications of Gd (III) retention and/or accumulation, particularly in vulnerable conditions and repeated exposures.