Thursday, January 24, 2019

Multiple sclerosis and gadolinium contrasting agents

About six months ago, IPBiz posted about possible adverse clinical effects arising from the use of some linear gadolinium contrasting agents in magnetic resonance imaging (MRI):

From ITNonline:

August 29, 2017 — The European Medicines Agency (EMA) issued a final opinion that recommended restricting the use of some linear gadolinium-based contrast agents (GBCAs) and suspending the marketing authorizations of others, while supporting the continued use of macrocyclic GBCAs.

Importantly, the EMA confirmed that “there is currently no evidence that gadolinium deposition in the brain has caused any harm to patients; however EMA has recommended restrictions for some intravenous linear agents in order to prevent any risk that could potentially be associated with gadolinium brain deposition.”

From Eur Radiol. 2018 Apr;28(4):1579-1584. doi: 10.1007/s00330-017-5065-8. Epub 2017 Oct 23:

The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) earlier this year recommended to suspend some marketing authorisations for Gadolinium Containing Contrast Agents (GCCAs) based on linear chelators due to the potential risk of gadolinium retention in the human body. These recommendations have recently been re-evaluated by EMA's Committee for Medicinal Products for Human Use (CHMP), and confirmed the final opinion of the European Medicines Agency. This editorial provides an overview of the available GCCAs and summarises the recent evidence of gadolinium retention. Moreover, a critical appraisal of the strengths and limitations of the scientific evidence currently available on gadolinium retention is given.

link: Linear gadolinum imaging agents and clear and convincing evidence

It may be that in the year 2019 not everyone has gotten the message about these certain linear gadolinium contrast agents.

As to risks, consider the mechanism. The blood-brain barrier is hydrophobic and repels hydrophilic moieties (eg, contrasting agents). A breakdown in the barrier allows intrusion of hydrophilic entities. The contrast agent, with paramagnetic Gd+3, shortens the T1's of nearby protons, allowing them to be perceived in this particular NMR sequence. HOWEVER, when the contrast agent itself begins to breakdown (as it does for some linear agents), the matter of "where" the Gd+3 ends up is not so clear. If the Gd+3 remains in the brain, it will influence later MRI measurements.

See also the Nov. 2018 paper which concludes:

Increased signal intensity in the deep cerebellar nuclei of rats persists for at least 1 year
after administration of linear gadolinium-based contrast agents (GBCAs), in line with
persistent brain gadolinium concentrations with no elimination after the initial 5-week period.
The animals that received macrocyclic GBCAs showed an ongoing elimination of gadolinium from the
brain during the entire observation period.

Gregor Jost et al., Published Online:Nov 13 2018


Post a Comment

<< Home