Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents

Invest Radiol. 2017 Jun;52(6):317-323. doi: 10.1097/RLI.0000000000000374.


For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was convincing evidence of gadolinium deposition in the brain months after injection of these linear agents. Primovist/Eovist (gadoxetic acid disodium) will remain available, being used at a lower dose for liver imaging, because it meets an important diagnostic need. In addition, a formulation of Magnevist for intra-articular injection will remain available because of its very low gadolinium concentration.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Brain / drug effects
  • Brain / metabolism*
  • Contrast Media / adverse effects
  • Contrast Media / pharmacokinetics*
  • Europe
  • Gadolinium / adverse effects
  • Gadolinium / pharmacokinetics*
  • Gadolinium DTPA / adverse effects
  • Gadolinium DTPA / pharmacokinetics
  • Humans
  • Injections, Intravenous
  • Magnetic Resonance Imaging
  • Marketing / legislation & jurisprudence*
  • Meglumine / adverse effects
  • Meglumine / analogs & derivatives
  • Meglumine / pharmacokinetics
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / pharmacokinetics
  • Pharmacovigilance*
  • Practice Guidelines as Topic*
  • Risk Assessment


  • Contrast Media
  • Organometallic Compounds
  • gadobenic acid
  • Meglumine
  • gadodiamide
  • Gadolinium
  • Gadolinium DTPA
  • gadoversetamide