Chelation Therapy for Rare Earth Element Toxicity: Current Evidence, Challenges, and Future Directions

The widespread and growing use of rare earth elements (REE) in modern technologies has raised concerns regarding human exposure and associated toxicological risks through occupational, environmental, and medical pathways, including mining, electronic waste, and gadolinium-based contrast agents in MRI procedures. This review evaluates REE toxicological profiles, focusing on their unique mechanisms, organ-specific effects, and therapeutic challenges. REE toxicity is primarily mediated through oxidative stress, mitochondrial dysfunction, and metal ion substitution, leading to multi-organ effects, impacting respiratory, cardiovascular, nervous, hepatic, and reproductive systems. Studies in human clinical data, animal models (e.g., rats, mice, zebrafish), and in vitro systems show adverse effects, although dose-specific data remain limited, with examples including gadolinium retention post-MRI and cerium exposure in occupational settings. Conventional chelators such as EDTA, DMSA, and DMPS demonstrate limited efficacy against most REE, with DTPA showing moderate potential particularly for gadolinium and cerium. The anticoagulant properties of lanthanides, arising from their antagonistic effects on calcium-dependent coagulation cascades, represent an additional toxicological concern that has been recognized for decades. Evidence from occupational studies, animal experiments, and clinical reports highlights the need for early exposure recognition, prevention, and individualized treatment strategies, including supportive care and REE-specific chelation when feasible. The absence of targeted regulatory frameworks and comprehensive clinical data hinders effective risk management. Chelator-assisted detoxification approaches show promise for addressing REE radionuclides from nuclear fallout, particularly for isotopes such as ¹⁴¹Ce, ¹⁴⁴Ce/¹⁴⁴Pr, and ¹⁴⁷Pm that become prominent in late-stage fallout scenarios. Future research priorities include developing novel REE-specific chelators, establishing evidence-based therapeutic protocols, and harmonizing international regulations. This review provides healthcare professionals, toxicologists, and researchers with an updated synthesis of current knowledge on REE toxicity and therapeutic strategies, emphasizing the urgent need for clinical innovation and regulatory reform to address this emerging public health concern.