NSF and Gadolinium

 

Risk of NSF by contrast agent

Do all MR contrast agents carry the same risk of NSF?  
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The vast majority of NSF cases have been reported with Ominscan™ (gadodiamide), while the second highest number have been reported with Magnevist® (gadopentetate). Optimark™(gadoversetamide) holds the non-enviable third position, a surprising result due to its relatively low market penetrance and use. 
Occasional confounded cases of NSF have occurred in patients receiving ProHance® (gadoteridol), MultiHance® (gadobenate), Dotarem® (gadoterate), and Gadavist® (gadobutrol). However, these patients all received two or more different gadolinium compounds and hence causation by a single agent could not be established.
To my knowledge, no cases of NSF have been reported with the newest gadolinium contrast media, Eovist® (gadoxetate) and Ablavar® (gadofosveset). However, only limited worldwide experience with these agents is available and they are being given in an “NSF-conscious” era, where high doses of gadolinium are avoided and careful scrutiny of renal function is undertaken prior to contrast administration.

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The high prevalence of NSF cases associated with Ominscan™ and Optimark™ is likely related to the fact that these drugs have relatively weak binding of gadolinium to the chelate.  This is reflected in the values of their thermodynamic stability constants, shown in the table right.  In that our current concepts of NSF pathophysiology relate to deposition of free Gd in tissues, it makes sense that contrast agents more likely to dissociate would carry a higher risk of the disease.

The relatively high numbers of NSF cases associated with Magnevist® is probably not explainable by weak ligand binding, since its dissociation constant is five orders of magnitude higher than Ominscan™ and Optimark™. One explanation is that Magnevist® may be overrepresented in the total number of reported NSF cases simply because of its dominant market share and high worldwide use.
In conclusion, even though some of the newer agents have not been directly implicated in the development of NSF, no gadolinium-based contrast formulation should be considered completely safe. Based on the available data, we avoid the use of OpitMARK™ and Omniscan™ in all patients, and Magnevist® in those with even mild renal insufficiency.  
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