Chelators: the Problem with Redistribution
There appears to remain a general misunderstanding on chelators. In this post I will briefly address the relative strength of the bonds between Gd and the common chelators: DTPA, EDTA, DMSA, DMPS.
As I reported in an early blog on the stability constants of these chelators looking at Gd (where available) and other heavy metals, DTPA has the highest stability constant for essentially Gd and all other heavy metals. What may not be generally understood is all these chelators will pick up what they are marketed to pick up (DMSA and lead) but also all the other metals, like Gd. Picking up metals is good, but redistribution is bad, and this is where individuals can have problems.
All chelators will drop off again some of the Gd that they have picked up, while still in the body. The amount they drop back off in the body is where the problem can be. This is redistribution. In fact this is why DMSA is marketed to remove lead, and EDTA not, even though EDTA has a higher stability constant than DMSA for lead. Ostensibly it is because EDTA can pick up lead from bone, and redistribute it in the soft tissues, whereas DMSA does not pick up lead from bone. Without studying the subject, I am a little dubious of this. It does illustrate though that the problem of redistribution of heavy metals has been recognized for some time.
In practical terms, what does this mean: my opinion is that even the best of chelators has some redistribution, and these are my estimates:
DTPA may redistribute 1% of the Gd it has picked up.
EDTA probably redistributes 30% of the Gd it picks up.
DMSA and DMPS probably redistribute 50% of the Gd they pick up.
This explains why I never recommend using other chelators in addition to DTPA. So I never recommend using DMSA if the GDD patients have co-existent elevated lead. DMSA does not pick up just lead, it picks up all heavy metals, and picks up Gd, but very inefficiently. As a result it likely causes much more harm than good. DTPA is much better at picking up lead as well.
The problem is where does the redistributed Gd go. Likely it goes to the most symptomatic soft tissue, to make the situation worse in that location, as this is where the bulk of the Gd went to in the first place, and probably retained in white blood cells such as macrophages.
Bottom line, only use DTPA for all heavy metals. It may turn out that other chelators have better stability constants (perhaps HOPO) or even the ligands of other GBCAs may have better performance, as some of them do have higher kinetic stability. This has to be balanced with how able they are to release their carrier cation and pick up Gd in vivo.
To stay tuned on the latest advancements: