iv DTPA: 3 administration techniques. Only one of which I use.

There are three approaches used for iv DTPA administration.

1. The first approach, which had begun use in the 1950s-1960s, was used for radio-active metal decorporation, specifically Plutonium. This was basically daily administration of iv ZnDTPA. Aerosolized ZnDTPA was also used- which makes enormous sense for a metal that inhalation has been the route of entry of the metal in the body..

This technique is optimal when the heavy metal in question creates severe destruction by its nature- in this case radiative decay and extreme cellular injury from that. The risk of irreparable tissue injury and patient death far outweigh any concern at the time, of putting an individual in electrolyte imbalance. This anyways can also be corrected by intermittent iv infusion or oral consumption of electrolytes. I actually would prefer Ca-DTPA over ZnDTPA for severe cases, because CaDTPA removes more of ther heavy metal by atleast two-fold. The downside of using CaDTPA is one has to for sure replenish electrolytes, would be not as essential with Zn-DTPA.

The upside with Gd, is that daily administration does avoid re-equilibration Flare.

The downsides include: i) that it requires prolonged continuous stay by the individual in the location of chelation, ii) there is time no allowance for re-equilibration, which bone removal benefits from, iii) if using Zn-DTPA it is unknown the effect of longterm high Zn serum level. After 1 does of Zn-DTPA the serum level of Zn is twice normal, but this returns to normal by natural homeostasis by 1 week. This is a remarkable feature of the body's natural ability to heal itself/ correct imbalances. But prolonged daily Zn-DTPA administration, often for weeks; the extent, duration and clinical effect of elevated Zn serum level, to my knowledge has never been documented. There must be limits to how much homeostasis the body can accomplish. Without this knowledge or documentation, I cannot advise it except for radio-active metal decorporation. I suspect a drip technique is used most often with daily chelator treatment regimen.

2. The second approach is injecting DTPA into the iv bag, and using a drip technique.

The advantage are: i) it does not involve much patient interaction by the chelating health care worker, just inject in the bag and let it drip, and ii) the Flare is considerably less. The reason the Flare is less is simple, it removes much less Gd, and almost no Gd from the deep interstitial tissue, which is the most important location to remove Gd from.

The best way to think of it is by analyzing how GBCA is administered in the first place. Almost always it is by a relatively fast machine power injection rate of 2 ml/sec. Why is GBCA administered this way? And why Iodine contrast and CT administered this way as well? Both agents with their respective imaging modalities started as iv drop infusion, but very quickly, with CT it took maybe 3 years, and with MRI maybe 1 year, that drip technique shows poor organ enhancement and poor pathology enhancement (or lack of enhancement) compared to fast bolus injection. This is because fast injection drives contrast into the interstitial tissue (also called extracellular matrix- ECM), which vastly improves enhancement of organs, tumors, and everything else important. The enhancement with iv drip is vastly inferior and these organs, tumors etc enhance to a much lesser extent. So pathology is difficult to impossible to see. This reflects that with iv drip most of the contrast stays in the vascular space.

The same is true therefore of the chelator, with a drip technique most of the agent stays in the intravascular space and little in the ECM, and none driven into the ECM. So essentially in simplistic but obvious terms: I want the chelator to follow the path of how the metal was delivered to begin with.

3. The third approach, is the most modern. It follows the principle of the removal chelator agent following the pathway and method of the delivery of the GBCA. By extension, this also suggests that with an agent that has been administered iv, like GBCA, at least the first 3 treatment sessions should also be by iv route.

I always use a split iv dose, with the concept that the second part of the injection removes Gd that may have been loosened by the first split injection but not removed. This likely especially benefits the removal of GBCAs that are still largely fully intact, which are Dotarem/Clariscan and Prohance. Since their removal is likely by levering fully intact GBCA from the body, by some fashion, likely facilitated by native biochemicals.

So split dose, is one variant on the bolus technique we standardly employ. The more recent additional variant, is starting with a much reduced volume of chelator, to see how the patient manages with Flare. Then increase chelator from there to patient tolerance, or rarely decrease even further if needed. Usually starting with just ZnDTPA, but occasionally with just CaDTPA. Sometimes interleaving both individual agents from one chelation session to the next. Although in general ZnDTPA is a much gentler chelation (less removal of Gd, minimal disturbance of native electrolytes)., in some individuals they may react more to ZnDTPA. This is for reasons that are not entirely clear, but may reflect perturbation of native metalloproteases or other Zn perturbations in the body, some individuals do better with just CaDTPA. Our original approach was very rigid, our current approach is very flexible.

This is our rationale for our approach to chelation. The chelator follows the route and the method of administration.

Richard Semelka, MD.