Long-term retention of gadolinium in the skin of rodents following the administration of gadolinium-based contrast agents

Several publications suggest a potential association between the administration of Gadolinium-based contrast agents (GBCAs) and the onset of a rare but serious disease, Nephrogenic Systemic Fibrosis (NSF). The aim of this study was to determine the elimination time-course of Gadolinium (Gd) from skin tissue after application of GBCAs in rats. Seven different marketed GBCAs were injected on five consecutive days at a dose of 2.5 mmol/kg bodyweight into the tail vein of Han-Wistar rats and the Gd concentrations were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in skin biopsies taken at various time-points up to a year after the last injection. Most of the administered Gd was eliminated from the skin within a time-period of about 2 months. However, the repeated administration of linear GBCAs resulted in long-term retention of a small portion of the administered Gd in the skin tissue of rats, with substantially higher values observed in animals treated with non-ionic linear agents than in those that received ionic linear GBCAs. Following treatment with macrocyclic GBCAs, Gd values in the skin were in the same range as observed in the controls from day 24 post-injection onwards. In summary, we observed a correlation between the complex stability of GBCAs and the amount of residual Gd in the skin up to a year after application of GBCAs.