Distribution and clearance of retained gadolinium in the brain: differences between linear and macrocyclic gadolinium based contrast agents in a mouse model

Objective: To investigate the distribution and clearance of retained gadolinium (Gd) in various parts of the brain after intravenously administering a Gd-based contrast agent (GBCA) in normal and renal failure mouse models. Methods: Two different mouse models: normal (n=12) and renal failure (n=12) were used. Clinical GBCAs (Gd-DTPA-BMA, 5 mmol kg(-1), or Gd-DOTA, 5 mmol kg(-1)) were intravenously administered five times per week for 4 weeks. Both groups were divided into two subgroups based on the time point for sample collection: 3 days (3d) and 45 days (45d) after the last injection. Normal saline (5 ml kg(-1)) was intravenously administered to mice of the control groups in the same manner. Samples of the following parts of the mouse brain were obtained on dissection: olfactory bulb, cerebral cortex, hippocampus, thalamus, mid-brain, cerebellum, pons and medulla. Gd-158 concentrations in each sample were quantified using inductively coupled plasma mass spectrometry. Results: The olfactory bulb had the highest Gd concentration in both Gd-DTPA-BMA and Gd-DOTA groups. Gd retention was higher in the Gd-DTPA-BMA group than in the Gd-DOTA group (p < 0.01). In the Gd-DTPA-BMA group, Gd retention in the 3d subgroups of normal and renal failure models were similar (p=0.4). At 45d, Gd in the Gd-DTPA-BMA group was not eliminated from the renal failure model (p=0.1), while that in the Gd-DOTA group was eliminated from both the normal and renal failure mouse models (p<0.01). Conclusion: Gd distributions in the brain for both groups were similar, regardless of the renal function and GBCA type. The Gd concentration was highest in the olfactory bulb of both groups. In the Gd-DOTA group, Gd was eliminated from the brain in both mouse models, while in the Gd-DTPA-BMA group, Gd clearance was limited. Advances in knowledge: Gd concentration in the brain was not affected by renal function. The clearance of Gd from linear GBCA was limited in both the normal and impaired renal function mouse models.