DTPA Chelation Therapy with Ancillary Treatment. Evaluation of Results. May 2021.
There are two elements to treatment for GDD (and actually all of the heavy metal Deposition Diseases) 1. remove the heavy metal, and 2. control the immune response of the host.
Background. Choice of Chelator
This critical point: the chelator used must have a high stability for the metal chelated. The stability constant should be known between chelator and the metals that are being chelated.
To illustrate: EDTA has a stability of 17 (10 to the power of 17) and DTPA has a stability of 22.46 with Gd. This means that DTPA is 300,000 times more stable with Gd than EDTA (yes I have those zeroes correct). This means that it can hold onto Gd much, much better than EDTA, and therefore redistribution is very minimal with DTPA and relatively prominent with EDTA - I estimate perhaps 1% redistribution with DTPA and 30% with EDTA. This does not mean that EDTA cannot pull a lot of Gd out of tissues, as urine Gd results show high urine Gd even with EDTA (and DMSA as well). So stability refers to hanging on to the metal, and does not mean ability to mine the metal out of tissue. The stability of Gd with DMSA and DMPS has not as yet been determined.. I am trying to obtain those numbers.
The best way to think of this is that the stability of the chelator of Gd out of tissues is exactly as important and same concept as stability of the GBCAs themselves. High stability GBCAs (thermodynamic stability): Dotarem, Prohance, Multihance, are preferred over lower stability agents: Omniscan and Optimark. In fact because of the stability issue, the European Medicine Agencies have banned the use of Omniscan and Optimark (and Magnevist) because of lower stability... But these agents are still much more stable than Gd-EDTA.
The importance of stability when considering a chelator to remove Gd (or other heavy metal) is of equal importance as stability is for an administered GBCA, if the stability of a chelator is unknown: it is like administering to a patient a GBCA for MRI study, and telling them this: "I will now inject you with Gd-XYTA. We have no idea how stable it is, but here we go" It would be unethical, perhaps criminal to do this with an MR contrast agent - the same is true with chelators to remove them.
So I hope this illustration makes this point clear.: the stability of a chelator with heavy metals deposited in the body is critical.
So DTPA is the most stable chelator available for Gd (HOPO is more stable still). But also important is that overall it is very stable for most other heavy metals. This is critical, as I have mentioned in atleast one earlier blog, because all chelators move all metals - but if they have low stability there will be a lot of redistribution. Everyone has atleast several metals in them: among them, everyone has lead (Pb).
So EDTA, DMSA, and DMPS will chelate Gd, but it is dirty chelation - meaning a lot of redistribution occurs. That is for example, Gd picked up in skin and dropped off in brain.