DTPA Chelation Radioactive Metals and Deposition Disease (Tcell allergic reactions)- Differences.

The original use, and FDA indications, for DTPA are for the removal of radioactive heavy metals, whereas the indication that I have been using DTPA for are for Gadolinium (and other heavy metal, eg: Lead) Deposition Disease states (AKA Tcell allergy or Tcell dysregulation). There are differences in how to perform DTPA chelation, and this is based primarily on what the reaction is that is being treated, and what the immune reactivity status is. In short, the following:

1. with radioactive heavy metals, the primary concern is the removal of radioactive particles rapidly , because the radioactivity directly kills host cells (cytotoxic) hence the ideal is to remove as much as possible as quickly as possible, and other considerations, such as electrolyte balance are secondary. This is not a Tcell dysregulation or allergy, so in the early published studies on this subject Flare was never likely present, and hence not described.

2. With Gadolinium Deposition Disease (and other Deposition Diseases) the primary concern is removing the heavy metal which has caused a Tcell allergic response. Removal soon following exposure (after 1 and to 2 months) can be disastrous as the host is in a state of heightened immunologic memory, and hence heightened immunological response to the removal of the heavy metal. Chelation removal generally may be problematic before at least 3 months has passed since exposure, and almost always should be combined with immune dampening, and always with immune dampening within 1 year of exposure.

Removal Radioactive Heavy Metals.

The likelihood of coexistent allergic response is rare. Chelation traditional has been day 1 Ca-DTPA, and then followed by daily Zn-DTPA. Since there should be no host Tcell allergy, then Flare reaction should be nonexistent, so daily chelation is feasible. In our experience Ca-DTPA removes basically twice as much heavy metal as Zn-DTPA, so I may prefer daily Ca-DTPA, and use a strategy like Ca-DTPA for two days, then third day electrolyte solution, and repeat this for 1 month. That may be less safe from an electrolyte balance position than daily Zn-DTPA, but I think removing rapidly heavy metal is a more important consideration.

The other interesting aspect of daily Zn-DTPA, which I am sure has never been looked at is: serum Zn level after just 1 dose of Zn-DTPA measures at a toxic level 1 day following Zn-DTPA, but return to normal by one week. This speaks of the incredible ability the body has to achieve homeostasis on its own. I think it may take 3 days to start returning to near normal. Now if this is just after 1 day of Zn-DTPA, what would the serum Zn look like if daily repetition of Zn is performed for many days in a row? And what does Zn toxicity look like?

A few centers in Europe have used a radioactive heavy metal strategy to remove Gd. I am not sure I agree with that, as above.

An interesting future direction, what about chelates of DTPA with other important native metals, to keep these in balance: Mn-DTPA and Mg-DTPA? It may be prudent to administer each one individually on different days. But what about one in the morning and another type in the afternoon, or could they all be mixed together like an electrolyte solution - this latter sounds a little unpredictable because a number of transmetalizations would be occurring, so in the mixture one would anticipate that the highest end concentration would be of the most stable chelator which would be Zn-DTPA. These ongoing transmetalizations conjure up the image of the witches in MacBeth posed in front of a huge bubbling cauldron.

Removal of Gd in a Deposition Disease State.

If you are 1 month out from developing GDD, delay removal until 3 months has passed. We are in the process of evaluating chelation immediately and within 1 month of GBCA injection (stay tuned). A strategy of Ca- day 1 and Zn day 2 we have used most often and spaced between 1-4 weeks, with 3 weeks seeming quite ideal. Currently we generally do the first chelation with lower chelator dose and high steroid dose. We also do any combination of amounts of chelator or types of chelator, but if we use both, Zn-DTPA always follows Ca-DTPA, because we want the Zn-DTPA to restore the total body Zn that will have been partly depleted by Ca-DTPA. The major concern is the Flare reaction. Unlike with radioactive heavy metals the primary disease causing event is not so much the direct effects of Gd (although insertion of Gd into pathways as a substitute for Ca or Na, is an important cause of disease), the primary cause is likely the effect of cytokine and other inflammatory products released by Tcells (and also their associates). As a result it is absolutely imperative to control the inflammatory effect of chelation concurrently with chelation, that arises secondary to Tcells reacting to the movement of Gd.

So ideal is chelation being 3 months (at the earliest, caveat very early chelation under evaluation) following exposure and combining chelation removal with immune reaction suppression. Spacing sessions 1-4 weeks apart also allows for homeostatic return to normal electrolyte levels, but also importantly it makes use of le Chateliere's principle of Gd moving from bone back to skin that begins in earnest at about 3 weeks post chelation, and probably peeks at about 3 months post chelation. In each chelation most of the Gd removed is from skin and soft organs, and relatively little from bone. So with each cycle of chelation some Gd has moved from bone to skin, allowing enhanced removal of Gd from the body. No time lapse between chelations has the effect of minimizing the important contribution of le Chateliere to deplete the largest repository of Gd- the bony skeleton.

Removal of Gd from a Storage Condition State (GSC). By definition Gd Storage Condition does not result in an immunological reaction, hence Flare is not a concern, and hence removal should be possible immediately following GBCA injection and at any time following the injection. So removal in the GSC state essentially can be identical to removal of heavy metals. Interestingly, we have observed in our cytokine studies that not showing a clinical allergic reaction does not mean that the Gd is being completely ignored by Tcells, which is what I originally thought was happening. In reality the exact opposite is occurring Tcells are paying very close attention in GSC, they are just sending out calming/ suppressor cytokines rather than pro-inflammatory cytokines.

So, in conclusion, DTPA chelation for radioactive metals is a very different approach than removing metals in a Deposition Disease state. One strategy should not be employed for the other indication.