Gadolinium-Based Contrast Agent-Related Toxicities
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In recent years, gadolinium-based contrast agents have been associated with different types of toxicity. In particular, nephrogenic systemic fibrosis, a progressive sclerotic-myxedematous systemic disease of unknown etiology, is related to gadolinium-based contrast agent administration in patients with kidney dysfunction. More recently, evidence of magnetic resonance signal intensity changes on pre-contrast T1-weighted images after multiple gadolinium-based contrast agent administrations resulted in the hypothesis of gadolinium brain accumulation in patients with normal renal function, subsequently confirmed in pathological samples. However, there is limited current data and further investigations are necessary before drawing definite conclusions on the clinical consequences of gadolinium-based contrast agent accumulation in human tissues and particularly in the brain. Gadolinium-based contrast agent-related toxicity appears connected to molecular stability, which varies together with the pharmacokinetic properties of the compound and depends on the individual characteristics of the subject. During a lifetime, the physiological changes occurring in the human body may influence its interaction with gadolinium-based contrast agents: the integrity and developmental stage of the organs has an effect on the dynamics of gadolinium-based contrast agent distribution and excretion, thus leading to different possible mechanisms of deposition and toxicity. Therefore, the aim of this work is to discuss the pharmacokinetics and pharmacodynamics of gadolinium-based contrast agents, with a special focus on the brain, and to explore potential predominant gadolinium-based contrast agent-related toxicity in two cornerstone periods of the human life cycle: fetal/neonatal and adulthood/aged.
Compliance with Ethical Standards
No sources of funding were received for the preparation of this article.
Conflict of interest
Luca Pasquini, Antonio Napolitano, Emiliano Visconti, Daniela Longo, Andrea Romano, Paolo Tomà, and Maria Camilla Rossi Espagnet have no conflicts of interest directly relevant to the content of this article.
- 22.esur.org. ESUR guidelines. 2016. http://www.esur.org/esur-guidelines/. Accessed 18 Feb 2018.
- 23.ema.europa.eu. European Medicines Agency. 2016. http://www.ema.europa.eu/ema/. Accessed 18 Feb 2018.
- 24.Fda.gov. US Food and Drug Administration. 2016. http://www.fda.gov/. Accessed 18 Feb 2018.
- 48.Rossi Espagnet M, Bernardi B, Pasquini L, Figà-Talamanca L, Tomà P, Napolitano A. Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children. Pediatr Radiol. 2017;47:1345–52.CrossRefPubMedGoogle Scholar
- 50.Bjørnerud A, Vatnehol S, Larsson C, Due-Tønnessen P, Hol P, Groote I. Signal enhancement of the dentate nucleus at unenhanced MR imaging after very high cumulative doses of the macrocyclic gadolinium-based contrast agent gadobutrol: an observational study. Radiology. 2017;285:434–44.CrossRefPubMedGoogle Scholar
- 56.Frenzel T, Apte C, Jost G, Schöckel L, Lohrke J, Pietsch H. Quantification and assessment of the chemical form of residual gadolinium in the brain after repeated administration of gadolinium-based contrast agents: comparative study in rats. Invest Radiol. 2017;52:396–404.CrossRefPubMedPubMedCentralGoogle Scholar
- 57.Gianolio E, Bardini P, Arena F, et al. Gadolinium retention in the rat brain: assessment of the amounts of insoluble gadolinium-containing species and intact gadolinium complexes after repeated administration of gadolinium-based contrast agents. Radiology. 2017;285(3):839–49.CrossRefPubMedGoogle Scholar
- 58.Iliff J, Wang M, Liao Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid b. Sci Transl Med. 2012;4:147ra111.Google Scholar
- 61.Chung MC-M. Structure and function of transferrin. J Chem Inf Model. 1989;53:160.Google Scholar
- 73.Zou Z, Zhang H, Roditi G, Leiner T, Kucharczyk W, Prince M. Nephrogenic systemic fibrosis. JACC Cardiovasc. Imaging. 2011;4:1206–16.Google Scholar
- 76.Steger-Hartmann T, Raschke M, Riefke B, Pietsch H, Sieber MA, Walter J. The involvement of pro-inflammatory cytokines in nephrogenic systemic fibrosis: a mechanistic hypothesis based on preclinical results from a rat model treated with gadodiamide. Exp Toxicol Pathol. 2009;61:537–52.CrossRefPubMedGoogle Scholar
- 82.European Medicines Agency. EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans. 2017. EMA/625317/2017. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/gadolinium_contrast_agents_31/European_Commission_final_decision/WC500240575.pdf. Accessed 18 Feb 2018.