Does oxalic acid disassemble all GBCAs in humans? I don't know, but I am doubtful

Wisdom comes with age in some, in many they just become old and crazier.

Richard Semelka

The team of Wagner recently published an interesting paper in the MRI journal on the disassembly with oxalic acid of not only Omniscan (which in unremarkable, since it is the least stable GBCA) but also of Dotarem (which would be remarkable since this is the most stable GBCA). The question I have though, does this occur to any extent in humans?

Scientifically one always has to keep in mind the following: lab studies are very important at showing concepts, animal studies go further and are interesting as they illustrate if certain lab findings occur in living organisms. The larger the animal model (dog, pig, monkey, ape) the closer to the human experience. Rodents are used most frequently for animal models, because they can be modified relatively easily genetically, are relatively cheap in all regards, and people are not so fondly attached to a rat as they may be to a dog, and rat studies upset people less than dog studies. I have never done animal studies because, especially with the dog, I could not harm them. Throughout my career I have focused on humans... also because all of my clinical work is on humans, and none on rats or dogs.

As I have written in earlier blogs, a novel finding in an individual group should spark interest. But for me to be convinced this is something really worth looking into (if the finding is not something empirically obvious, such as DTPA removes Gd) then I would want to see at least 3 independent groups making this finding, and ultimately then observing this in humans.

For starters in skepticism, I am surprised that the contrast imaging manufacturers would not have already observed this. I know what you may be thinking, Dr Semelka is giving them too much ethical credit. But that said, the contrast research teams of Bayer, Guerbet, and Bracco are dedicated scientists. This I know from personal experience with them.

My personal theory, and I say this as the world authority on the total Gd picture, is that the fully intake stable GBCAs are eliciting the chronic immune/toxic reaction of GDD when Dotarem or Prohance are the sole causative agent of GDD. It is not Gd disassembled by oxalic acid, or disassembled Dotarem because of poor construction (a bad batch) or poor or lengthy transport or storage (heated up, old Dotarem). It is fully intact Dotarem that the genetic and physiologic environment at the time of injection has caused the immune system to react violently against it, and allowed the opening of the evil Pandora's box to the 100 or so physiological interferences of Gd in the body. To use a crude, but memorable, comparison, these GBCAs are small molecules so I think the immune cells in humans recognizes the Gd within them, just as heterosexual human males have interest and recognize what is beneath when they watch a wet t-shirt competition- the wet t-shirt is like a small molecule. Ok, now you have that image in your head when you think of GBCA molecules.

The way to test this is relatively simple, and I have been talking to testing companies about this. Chelation with DTPA does remove Gd in people who have received just Dotarem and Prohance, so speciation of the Gd that comes out should inform noninvasively if it is intact Dotarem/ Prohance or Gd disassembled from them... Maybe Guerbet and Bracco, not me, should do that study. But I am prepared to do it. It just takes time and money.

Interestingly, when DTPA chelation is performed in the setting of just Dotarem or just Prohance the amount of Gd removed compared to pre-chelation native elimination is relatively small. An increase of maybe two - four fold is typical. However in the occasional individual the amount removed in 20 fold. Now two possibilities here: either they didn't get Dotarem but another agent, like Multihance (maybe this is more probable) or the Dotarem has been disassembled by something, and this something may be oxalic acid.

Final observation, if oxalic acid is actually disassembling even the most stable agents in vivo in humans it means that chelation will be even better at removing the Gd, than if it wasn't happening.

Richard Semelka, MD