Gadolinium. How much is removed with chelation?
The question on all patients' minds with GDD (or other heavy metal deposition disease) is how much Gd is removed with chelation. As an important aside, an interesting aspect of retained Gd, is each organ system will have its own Gd retention, own durability of retention, and own expression of toxin-related physiology and symptoms, very much analogous to CT and medical radiation exposure: each organ system has its own risk of radiation sensitivity and malignancy development, which is captured in estimation as radiation exposure with mSievert measurements.
There are an enormous number of variables in play in answering this question. A number are listed here, with the more important variables described is the first grouping. The assumption is that an effective chelator is used. Presently the most effective is iv DTPA. With the use of less effective chelators the amount removed is variable but less, and the amount redistributed can be enormous. To use a chelator in a medical setting for removal of Gd the stability constant must be known.
Most important variables:
How many GBCA injections have been made.
What category of GBCA: linear (more Gd is removed), stable macrocyclic (less Gd removed).
How long ago were the GBCAs administered. More recent, comparatively more Gd removed than > 2 years.
Spacing between chelation sessions: 1 week spacing, less Gd removed (from bone reservoir), but less re-equilibration. Flare, 4 week spacing more Gd removed (from bone reservoir) and more re-equilibration Flare..
Volume of chelator used
less important variables.
co-existent other metals
Optimal timing for chelation is between 3 months - 2 years after the development of GDD. Perhaps super-optimal is chelation within one week, and ultra-ideal within 1 day. Note these latter have not been tested.
Jumping to the end of the tennis match. Use of full dose Ca-DTPA day 1 and full dose Zn-DTPA day 2. Approximately 10% of the retained Gd present is removed if the agent is linear. Approximately 2-5% is removed if the agent is a durable macrocyclic.
Combining this information with an earlier blog that describes the amount of Gd retained in the body at certain time points:
Example: a one lifetime dose of Omniscan or Multihance has been administered and chelation done at 1 year.: 2% of administered Gd has been retained in this setting. First chelation removes 10% of retained Gd, so 1.8 % left. Second chelation removes 10% which leaves 1.8% - 0.18% = 1.62% left, and so on.
Example: a one life time dose of Dotarem/Clariscan given at one year. 1% of agent is retained. First chelation removes 5%, so after first chelation 0.95% of the agent is left behind, and so on.
It appears that in most individuals the Gd that is removed appears to be the most physiological active/ damaging Gd, explaining why although relatively little Gd is removed with macrocyclic agents, individuals none-the-less most often experience considerable improvement.
Richard Semelka, MD