Articles producció científicaCiències Mèdiques Bàsiques

Gadolinium toxicity: mechanisms, clinical manifestations, and nanoparticle role

  • Dades identificatives

    Identificador:  imarina:9462671
    Autors:  Domingo JL; Semelka RC
    Resum:
    Gadolinium-based contrast agents (GBCAs), essential for MRI, are facing renewed scrutiny due to gadolinium (Gd) retention and emerging toxicity profiles. While the link between less stable agents and Nephrogenic Systemic Fibrosis (NSF) in renal impairment is established, gadolinium (Gd) deposition is also observed in the brain, bone, and skin across all GBCA classes, even in patients with normal renal function. This finding has raised concerns and led to a concept of Gadolinium Deposition Disease (GDD). The present review synthesizes current evidence on clinical manifestations and underlying mechanisms. It highlights pathways beyond traditional transmetallation, particularly endogenous nanoparticle formation as a key mechanism for Gd release and retention, potentially challenging the stability assumptions for even macrocyclic agents. Structural factors (linear/macrocyclic; ionic/non-ionic) and stability parameters (thermodynamic log K; kinetic kobs) influencing risk are evaluated alongside regulatory responses. GBCAs should be viewed not as inert diagnostics but as agents with complex, cumulative biological interactions. Future research should focus on developing non-gadolinium alternatives, validating biomarkers for early detection of Gd retention, and conducting controlled trials on chelation therapy efficacy. Clinicians must balance the diagnostic benefits of GBCAs with potential long-term risks, ensuring informed patient consent and judicious use. Innovative approaches, such as Gd-grafted nanodiamonds with high relaxivity and enhanced safety via polyvinylpyrrolidone (PVP) coating, may offer alternatives to traditional GBCAs by reducing toxicity risks. Manganese-based contrast agents, such as Mn-PyC3A, show promise as safer alternatives due to efficient renal and hep
  • Altres:

    Autor segons l'article: Domingo JL; Semelka RC
    Departament: Ciències Mèdiques Bàsiques
    Autor/s de la URV: Domingo Roig, José Luis
    Paraules clau: T1-weighted mr-images; Signal intensity changes; Repeated administrations; Physicochemical properties; Nephrogenic systemic fibrosis (nsf); Nephrogenic systemic fibrosis; Nanoparticles; Magnetic-resonance; Imaging contrast agents; Human seru; Globus-pallidus; Gadolinium-based contrast agents (gbca); Gadolinium toxicity; Gadolinium deposition; Dentate nucleus; Chelate stability; Chelate stabilit
    Resum: Gadolinium-based contrast agents (GBCAs), essential for MRI, are facing renewed scrutiny due to gadolinium (Gd) retention and emerging toxicity profiles. While the link between less stable agents and Nephrogenic Systemic Fibrosis (NSF) in renal impairment is established, gadolinium (Gd) deposition is also observed in the brain, bone, and skin across all GBCA classes, even in patients with normal renal function. This finding has raised concerns and led to a concept of Gadolinium Deposition Disease (GDD). The present review synthesizes current evidence on clinical manifestations and underlying mechanisms. It highlights pathways beyond traditional transmetallation, particularly endogenous nanoparticle formation as a key mechanism for Gd release and retention, potentially challenging the stability assumptions for even macrocyclic agents. Structural factors (linear/macrocyclic; ionic/non-ionic) and stability parameters (thermodynamic log K; kinetic kobs) influencing risk are evaluated alongside regulatory responses. GBCAs should be viewed not as inert diagnostics but as agents with complex, cumulative biological interactions. Future research should focus on developing non-gadolinium alternatives, validating biomarkers for early detection of Gd retention, and conducting controlled trials on chelation therapy efficacy. Clinicians must balance the diagnostic benefits of GBCAs with potential long-term risks, ensuring informed patient consent and judicious use. Innovative approaches, such as Gd-grafted nanodiamonds with high relaxivity and enhanced safety via polyvinylpyrrolidone (PVP) coating, may offer alternatives to traditional GBCAs by reducing toxicity risks. Manganese-based contrast agents, such as Mn-PyC3A, show promise as safer alternatives due to efficient renal and hepatobiliary elimination, even in renal impairment, as demonstrated in rat models.
    Àrees temàtiques: Toxicology; Saúde coletiva; Química; Psicología; Odontología; Medicine (miscellaneous); Medicina veterinaria; Medicina iii; Medicina ii; Medicina i; Interdisciplinar; Health, toxicology and mutagenesis; General medicine; Farmacia; Engenharias iii; Engenharias i; Ciências biológicas iii; Ciências biológicas ii; Ciências biológicas i; Ciências ambientais; Ciência de alimentos; Biotecnología; Biodiversidade
    Adreça de correu electrònic de l'autor: joseluis.domingo@urv.cat
    Data d'alta del registre: 2025-08-02
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://link.springer.com/article/10.1007/s00204-025-04124-x
    Referència a l'article segons font original: Archives Of Toxicology.
    Referència de l'ítem segons les normes APA: Domingo JL; Semelka RC (2025). Gadolinium toxicity: mechanisms, clinical manifestations, and nanoparticle role. Archives Of Toxicology, (), -. DOI: 10.1007/s00204-025-04124-x
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    DOI de l'article: 10.1007/s00204-025-04124-x
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2025
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Health, Toxicology and Mutagenesis,Medicine (Miscellaneous),Toxicology
    T1-weighted mr-images
    Signal intensity changes
    Repeated administrations
    Physicochemical properties
    Nephrogenic systemic fibrosis (nsf)
    Nephrogenic systemic fibrosis
    Nanoparticles
    Magnetic-resonance
    Imaging contrast agents
    Human seru
    Globus-pallidus
    Gadolinium-based contrast agents (gbca)
    Gadolinium toxicity
    Gadolinium deposition
    Dentate nucleus
    Chelate stability
    Chelate stabilit
    Toxicology
    Saúde coletiva
    Química
    Psicología
    Odontología
    Medicine (miscellaneous)
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    Health, toxicology and mutagenesis
    General medicine
    Farmacia
    Engenharias iii
    Engenharias i
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciência de alimentos
    Biotecnología
    Biodiversidade
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