Ca- Disodium EDTA, my recommended protocol with DTPA in short supply

With DTPA presently unavailable in the USA - available everywhere else in the world. This ofcourse is unacceptable, but the present reality. I have devised an alternative approach using Ca- disodium EDTA. The rationale for regimen differs for DTPA and EDTA, and I will explain the rationale for EDTA below.

EDTA stability constant is 17 with Gd, while DTPA is 22.5- DTPA roughly 500,000 times more stable with Gd than EDTA. This means that re-distribution is much more of an issue with EDTA than with DTPA. Redistribution is the chelator picking up Gd then immediately re-releasing it.

Also it must be clear that adding in additional agents to the chelator has not been validated, and therefore not legally recommended. Beyond that I do not recommend adding in additional agents as I do not know how they will react with EDTA (the same logic I use with DTPA. So I estimate that with EDTA approximately 20-25% of Gd picked up is redistributed. The amount with DTPA is vastly less, likely in the range of 1%. So the below regimen takes into consideration dealing with redistributed Gd.

Additional note is the advantage of DTPA over EDTA is relatively minimal so the use of EDTA for Lead is also fine. DTPA 18.6, EDTA 18 thermodynamic stability. For organic Mercury both are about the same at 17.

The other note is that Gd incorporation into the body is by rapid iv administration, which is not the case for any other metal. To capture Gd in this setting, rapid bolus injection of the chelator is necessary.

Primary distribution of Gd therefore reflects this rapid injection, with a sizable portion deposited into the extracellular matrix (ECM)AKA interstitial space. This is not the case with other metals. Secondary distribution rel;fects movement of Gd between reservoirs while the large amount of retained Gd is spontaneously removed, and le Chatelier's principle drives that. Gd moving from reservoirs with larger amounts and moving to regions with lesser amounts, following a gradient of concentration specific to Gd. Tertiary distribution occurs secondary to the use of an effective chelator, and essentially greatly magnifies the process involved in secondary distribution. The use of a less effective chelator results in a pattern that could be termed quaternary. , and much of the Gd in this distribution is vessel wall based in the short term. The EDTA regimen takes into consideration quaternary redistribution on day 2.

Only Ca-disodium EDTA should be used.

Regimen EDTA

Day 1.

iv tubing and normal saline as with Gd regimen.

Steroid injections as with Gd regimen.

Split injection of a 5 ml vial (2.5 ml injection) given as two boluses spaced 20-30 minutes apart.

Day 2

iv tubing and normal saline as with Gd regimen

11/4 dose steroid injection

1/4 vial (1.3 ml) of EDTA injected into iv normal saline (500 ml) bag administered at a moderate drip rate.

Explanation:

The two boluses are designed to chase down the Gd originally administered as a rapid bolus. The second injection also will pick up some Gd redistributed from the first bolus.

Day 2 chelation is specifically designed to capture redistributed Gd as the sole purpose. A drip technique is used so that the EDTA will primarily stay in the vascular space, and pick up Gd along the vessel walls from the quaternary distribution. A much lower volume of EDTA is used in day 2 (different from DTPA regimen) because the primary intention is to capture Gd that has been redistributed, and not to contribute more Gd redistribution if larger volume or bolus technique is used.

Chelation as performed by practices for Lead and Mercury is unchanged from what practices usually do, and the treatment is appropriate. Note that addition of additional chemicals is not recommended. Bolus injection is not essential since the heavy metal has been incorporated by a non forced mechanism Inclusion of an occasional bolus may be of value to ensure some capture of ECM metals are captured.

Richard Semelka, MD