What MRI agent would Dr Semelka get if he had to get a GBCA enhanced MRI Study?

What MRI agent would I get if I had to get a GBCA-enhanced MRI?

This may be one of the more important generic posts that I have written. What is important when getting advice is to know what base of knowledge or credentials the adviser speaks from. So I am not an influencer among the many who populate social media, whose credentials generally lie in the number of followers they have, which in general is completely untied to knowledge. This is coming from the world authority on the field of Gadolinium. There are readers who may be shocked that I would say such a thing, interpret it as Narcissism or arrogance. But in this case it is neither, just the simple facts of the number and importance of articles written in peer-reviewed literature, text-books, presentations... but mainly peer-reviewed literature which is the gold standard for academic accomplishment, over 36 years at the top of the game. Just the facts. I have written m:re, and more important articles than anyone on Gd, the Good the Bad and the Ugly.

I will get another shocking point out, before I go to the MR agents. I am providing my opinion without any financial benefit from the manufacturers of the agents. No fancy hotels, no fancy restaurants, no first class airflights, not even a coupon for a meatball sub at Jersey Mikes. As impossible as it seems in this modern age, the advice I am giving you is devoid of any personal benefit. In fact, in recent years, in what I consider their economics-minded folly, many of my former friends company people who had at one time love me, now .. I think hate too strong a word.... maybe dislike me, because I have championed the diagnosis of Gadolinium Deposition Disease, and have also done it for the unthinkable reasons of: its the truth, it benefits everyone, and it is exactly in opposition to my financial interests.

Then the other shocking point, GDD is more common and hence more important a serious persistent adverse reaction than NSF. GDD is a toxicity like any other heavy metal toxicity, but NSF is something different. It is not described for any other heavy metal. This will be the subject of future writings. One side bar of relevance, a number of less informed individuals think that GDD should be called Toxicity, since that is what all other heavy metals are called... The issue is not that GDD should be called Gd Toxicity, to use just one other heavy metal as an example, but Lead toxicity should be called Lead Deposition DIsease. One important reason, beyond it is the most correct name, is then what do you call the 99.9% of people with Lead in them who are not sick from Lead: 'dudes with Led in 'em and ain't sick'. The correct designation of the majority, if they are not sick, is that they have Lead Storage Condition.

As the treatment for GDD is chelation with a chelator with strong binding affinity for Gd, then a consideration for a GBCA agent has to take into consideration that it should be somewhat readily removable.

Most of my focus has been on chelators in the recent past, but from the perspective of an MR agent, the critical property is T1 relaxivity. This not only allows for maximal enhancement differentiation between normal and diseased tissues but also allows for less agent administered. This translates to less agent deposited.

Some additional other shocking point to mention, again,

All Gd agents leave a little Gd behind in the individual for their lifetime.

All GBCAs have the propensity to cause GDD.

One, not so shocking point, I am not convinced that there is any fundamental difference in whether any brand results in less (or more) cases of anaphylactoid acute hypersensitivity reaction (AAHR). At this time I believe there is no fundamental difference in whether any cause more or less. Some believe that if AAHR has arisen from one brand of agent, another brand of agent may be safe to use. I would not bank on that for myself. This last subpoint may be slightly shocking to some radiologists.

All agents, outside of GDD and NSF are fundamentally safe. This means the ligands are fundamentally safe on their own. They are designed for safety and removability.

So the decision for which agent I would have administered on myself, knowing more than anyone else (and also importantly having no financial incentive), involves the consideration of T1 relaxivity on the imaging side, therefore better enhancement and less agent used, general adequate safety profile (also on imaging side), and at least moderate extent of removability (on the potential side of, if I needed to remove it) is:

Gadopiclenol

It is a macrocyclic agent, it has very high T1 relaxivity, so given in a smaller dose, and has mildly low intrinsic bonding strength (thermodynamic stability), with very good kinetic stability. That combination of lower thermodynamic stability and higher kinetic stability than DTPA actually is an ideal combination for safety (high kinetic stability) and removability (lower thermodynamic stability) than DTPA.

#2 Gadavist

For the same reasons as Gadopiclenol, but with lesser T1 relaxivity, and slightly higher thermodynamic stability.

#3 Multihance

Multihance also for historic reasons I am fond of. But it has higher T1 relaxivity. It also has some hepatobiliary elimination, which is important if kidney function is mildly abnormal.

#4 Dotarem/Clariscan and Prohance

Extremely stable. Leave less behind. But the secondary consideration is they are removed in the least amount by chelation - but still sufficient removal to result in signiifcant recover with GDD.

So, if I was concerned about GDD (and NSF) I would request Gadopiclenol. It checks off the important boxes for imaging and safety-ish.

Richard Semelka, MD