Chelation is like a Magnet Crane Arcade Game.
The more well known Crane Arcade game is the Claw Crane Arcade Game, and ofcourse chelator is derived from Greek word for Claw, but magnetic forces are involved with chelation in humans so the Magnet form of the Crane Arcade Game is a more close comparator.
As with the magnet crane game, the more powerful the magnet of a chelator (the higher the stability constant) the better able is the magnet crane at picking up the toy (which also has a small magnet on it). So DTPA has 300,000 times greater stability with Gd, than EDTA, and much higher still than DMSA and DMPS. So DTPA is a much better magnet to pick up the Gd, and it turns out lead (Pb), than the others, then drop it in the vascular circulation (the chute in the crane game) to the kidneys - into urine and out with urination (receiving the toy at the end of the chute).
So the analogy still holds with considering linear vs macrocyclic agents, linear agents the Gd is closer to the surface, therefore the magnet of the crane can lock on to the Gd magnet more strongly, and in the case of linears the magnet of the crane gets dropped off with the toy into the chute. The macrocyclic molecules are still quite small, so the magnet of the Gd is not so far from the surface, so a powerful magnet on the crane can still pick it up and drop it in the chute (circulation). It is not known if the chelator though just levers the Gd out of the tissues in its intact GBCA form and leaves it to travel to the kidneys on its own or whether it stay piggybacked on the intact GBCA. It is also not clear if perhaps the least thermodynamically stable of the macrocyclics, Gadavist, may partially break down, exposing more of the Gd to the chelator. This way it may explain why Gadavist appears to experience greater elimination with chelation than Dotarem and probably Prohance. as well., Or if the entire size of the Gadavist molecule is smaller, than Dotarem or Prohance, allowing more magnetic tugging of it out of the tissues.
At this point many of the scientific elements are still observational and not experimentally shown. But is is not unique to chelation and Gd that observational leads the way to understanding. That has been also true for the vast majority of drugs. Only recently has the activity of many psychiatric drugs been understood, also how acetaminophen works; and the method of action of the majority of anesthetic drugs remains unknown... but they do work. So I am not waiting for the scientific questions to be answered. I treat patients with the best method available and modify that treatment in the best way possible, and I am not waiting... like so many policemen in a Uwalde school > I am taking fast and accurate action to treat and cure patients. If HOPO or other oral chelators are as good or better, I will also change quickly to a better strategy.
Richard Semelka, MD