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

The accelerating integration of rare earth elements (REEs) in advanced technologies has generated rising concern over human exposure and the attendant toxicological risks. This review presents an up-to-date synthesis of current evidence on REE toxicity across multiple exposure pathways, including inhalation, ingestion and occupational contact, providing an integrative perspective from human clinical data, animal models and in vitro systems. Distinct from traditional reviews, it critically appraises how REE-specific mechanisms, such as oxidative stress, mitochondrial dysfunction and metal ion substitution, produce multiorgan effects with clinical manifestations distinct from those of conventional heavy metals. A key novel finding is the pronounced therapeutic gap. Although chelation is well established for many toxic metals, effective chelation therapy for REE remains largely undeveloped, with current agents like DTPA showing limited efficacy, particularly for gadolinium and cerium, underscoring a major gap in clinical practice. The review highlights vital implications for clinicians, stressing the importance of early exposure recognition, tailored supportive care and the urgent development and validation of REE-specific chelators. Priorities for future research include creating novel chelation strategies and harmonizing international guidance to protect exposed populations. This synthesis aims to equip health professionals, toxicologists and policy-makers with actionable insight, emphasizing the clinical and regulatory urgency of increasing REE exposure and toxicity.