Brain Gadolinium Biodistribution, Clearance, and Retention Following High-Dose Contrast-Agent Exposure in Mice: A Multimodal Study

Abstract

We evaluated gadolinium biodistribution, clearance, and long-term brain retention following high-dose gadolinium-based contrast agent (GBCA) exposure in 90 mice. Macrocyclic and linear agents were assessed using particle-induced X-ray emission (PIXE) alongside complementary elemental, imaging, and histological methods. Following intravenous administration, gadolinium was detected in blood and multiple tissues during the acute phase, with declining blood levels and detectable urinary excretion. No brain Gd signal was detected by PIXE at the long-term endpoints following single exposure. Repeated-exposure findings were descriptive because the individual subgroups contained only 1–3 animals. Endpoint MRI showed no apparent persistent signal changes, and H&E examination showed preserved tissue morphology. Metallothionein staining varied qualitatively, whereas Iba1 staining showed no apparent increase in microglial activation. Intraperitoneal administration produced no detectable blood gadolinium at the 1-h sampling timepoint. These findings characterize high-dose experimental exposure and support the feasibility of multimodal assessment of gadolinium biodistribution. Negative findings do not exclude residual Gd below the detection capabilities of the methods used.