Analysis of retention of gadolinium by brain, bone, and blood following linear gadolinium‐based contrast agent administration in rats with experimental sepsis

Abstract

Purpose It is important to identify populations that may be vulnerable to the brain deposition of gadolinium (Gd) from MRI contrast agents. At intervals from 24 hours to 6 weeks following injection of a linear Gd contrast agent, the brain, blood and bone content of Gd were compared between control rats and those with experimental endotoxin‐induced sepsis that results in neuroinflammation and blood–brain barrier disruption. Methods Male rats were injected intraperitoneally with 10 mg/kg lipopolysaccharide. Control animals received no injection. Twenty‐four hours later, 0.2 mmol/kg of gadobenate dimeglumine was injected intravenously. Brain, blood, and bone Gd levels were measured at 24 hours, 1 week, 3 weeks, and 6 weeks by inductively coupled plasma mass spectroscopy. Results Blood Gd decreased rapidly between 24 hours and 1 week, and thereafter was undetectable, with no significant difference between lipopolysaccharide and control rats. Brain levels of Gd were significantly higher (4.29‐2.36‐fold) and bone levels slightly higher (1.35‐1.11‐fold) in lipopolysaccharide than control rats at all time points with significant retention at 6 weeks. Conclusion Experimental sepsis results in significantly higher deposition of Gd in the brain and bone in rats. While blood Gd clears rapidly, brain and bone retained substantial Gd even at 6 weeks following contrast injection.

The Accumulation and Metabolism Characteristics of Rare Earth Elements in Sprague–Dawley Rats

“…Taken together, the mechanism and the relevance of REEs to health and disease in human body remain obscure. Rats are standard experimental animals for toxicological research for chemicals and are frequently used to observe the toxicological effects of trace elements [16][17][18]. Herein, the main purpose of the current study is to explore the accumulation characteristics of selected REEs in different tissues and organs, as well as the detoxification and elimination of high-dose REEs of Sprague-Dawley (SD) rats.…”

Gadolinium: pharmacokinetics and toxicity in humans and laboratory animals following contrast agent administration

“…This increase in bone retention persisted in the sepsis model and was significantly increased compared to controls up to 3 weeks, but by 6 weeks had reduced to levels comparable to those in sham groups given GBCAs, demonstrating a transient effect of sepsis on bone retention in this model. Although LPS and sham animals had equivalent bone gadolinium at 6 weeks, gadolinium was still detectable and did not show much clearance over time, although the mechanisms for this difference in retention are unknown (Damme et al 2020 ). This increased retention in the bone compared to other tissues has been hypothesised to be due to the bone serving as a reservoir or deep compartment for gadolinium, potentially resulting in the chronic and slow release of gadolinium over time as a result of the incorporation of gadolinium by osteoblasts into the bone matrix (Abraham et al 2008 ; Darrah et al 2009 ).…”

Retro-enantio isomer of angiopep-2 assists nanoprobes across the blood-brain barrier for targeted magnetic resonance/fluorescence imaging of glioblastoma

“…Gadolinium-based contrast agents (GBCA) are commonly used clinical MRI contrast agents, but recent studies have shown that their biosafety cannot be guaranteed, for this type of contrast agent is associated with renal fibrosis and the nervous system deposition. 40 Thus, the development of new contrast agents is one of the ways to improve biosafety. Previous report about biosafety of iron oxide nanoparticle (IONP) underlined that the biological safety of IONP was significantly better than that of GBCA, especially it would not cause nephrogenic systemic fibrosis or had a long retention in vital organs.…”