Total body heavy metal content. The crucial factor. Best surrogate: chelation sessions 1 month apart with effective chelator for that heavy metal, and 24 hr urine measurements, for some feces also.

One has to consider when one has toxic exposure to Gd (and other heavy metals)  the important perspective is total body heavy metal content. If urine Gd content remains relatively high over multiple chelations, this reflects that chelation is working. If chelation results in a constant relatively high Gd removal, this is not a bad thing, it means that total body Gd content is continuing to be reduced. The preservation of stable high Gd content in 24 hr urine reflects le Chatelier's principle (everything strives to be in equilibrium), in the case of Gd and lead (as examples) it is these metals are primarily removed by chelation from soft tissues and skin, and with time between chelations Gd and lead moves from bone back to these soft tissue organs. Total body Gd and lead content then is reducing when the 24 hr urine content starts dropping, which means the bone reservoir is depleting and can no longer restore a substantial amount of Gd to the soft tissues.

It should be noted that some of the Gd is actually eliminated as it moves from bone to soft tissue, as it passes through the circulation system (which is very good). 

Even with very potent chelators for Gd and lead, like DTPA, some early redistribution does occur (which is not a good thing), but this is vastly less redistribution, than that occurs with weaker chelators: EDTA has moderate redistribution, DMSA moderately severe redistribution. Redistribution is always bad.

Are there stronger chelators than DTPA, that should be effective in vivo at Gd and lead removal - yes. HOPO in theory may be better, but probably as an iv administration, other ligands also should be at least a little better.

Notes:

1. Shorter intervals between chelation will show less Gd in 24 hr urine, but this is a false demonstration of decreased total body content, it reflects not much redistribution has been allowed to occur. Probably 'complete' redistribution for the total body Gd content occurs at 1 year. However 1 month repeat chelation and urine studies results in a good approximation. So take in the interval between chelations when considering how much has been removed and how much may be left in the body.

   
   

2. Weak chelators will show low urine numbers post chelation, but this does not reflect less metal is present, it reflects a poor chelator has not removed much of that metal.

   
   

3. Gd, to date, may be unique among the heavy metals, in that if no further GBCA enhanced MRI has been done,, then no added heavy metal enters the system. Metals like lead will show continued additional entry of that heavy metal into the body, so reduction to near 0 will never occur. This reflects, as we are learning more and more about this, it seems that almost everything we eat now contains some lead in it. Lead will always be entering into the body.

Presently the best surrogate for understanding how much of a heavy metal is left in the body, is observing when Gd (or lead) begins to drop in 24 hr amount to near normal levels when an effective chelator is used.. THis reflects that total body content has now dropped dramatically.

Richard Semelka, MD