DTPA chelation. Does it just stir up Gadolinium? Mainly no, but a little yes- but this can be beneficial.

Does chelating Gd just stir up Gd? No, and a little yes, but carefully thought out chelation manages this to positive effect.

There probably is no better documentation of positive effect in medicine than measuring 24 hr urine for heavy metals pre- and post-chelation. Typically for most setting for most GBCAs (except Dotarem and Prohance) immediate postchelation urine shows something like 20 times to even 200 times greater Gd removal than prechelation. So this is scientific data that Gd has been removed. PERIOD. There is probably no better scientific data for anything we do in medicine than this.

Some have thought, well isn't this just the equivalent of 20 days of just being alive or 200 day? The answer to that is no. A good comparison is what I have used historically to describe radiation exposure and CT, where CT delivers for many studies around 4 mSev which is the equivalent of 1 year of just being alive, which is often how radiologists and CT technologists explain it to patients... so someone could say, well no big deal. But this is the more correct comparison that I use: if the daily temperature increases 1 degree Celsius every day, then one can say no big deal, but if you get in a 1 second blast 365 Celsius then you burn to a crisp instantly. That rem,oval of 20 or 200 times more Gd, first off is not a 1 day increase, but increased removal continues for atleast 1 week, and the removed Gd appears to be the most symptomatic. So this concept of just adding up days does not work PERIOD

Gd removal and Gd removal Flare, mainly good, as written in a number of blogs.

Gd Redistribution and Gd Redistribution Flare: Even with the best of chelators some of the Gd is redistributed (brought to a different tissue site in the body), probably atleast 1% of it - with the best of chelators. With poor chelators then the amount of redistribution is much more. In the case of Gd removal, using EDTA probably redistributes at least 30%, and DMSA atleast 50% and DMPS probably even more. Redistribution ( and Redistribution Flare) is always bad PERIOD But a tiny amount unavoidably occurs with even the best of chelators, but for the great majority this is of no clinical significance. That is why I never recommend the use of a chelator to remove Gd, where the log stability constant of the chelator with Gd in unknown. By never I mean NEVER

Re-equilibration is always an important effect when there are different durabilities of reservoirs of any toxin. There is ALWAYS variations in durability, meaning variation in how difficult it is to remove a toxin from a reservoir. For both Gd and Lead the most durable reservoir is bone, for other chemicals it is fat. So it is ALWAYS important to make use of re-equilibration (le Chateliere's principle) for removal of a toxin. This relies on relying on some time between chelation sessions to allow metal to move from durable reservoirs to less durable reservoirs. So this could be called in a simplistic understanding: stirring up Gd'. But this can be done with wisdom-sense, which is how I do it. So a rule of thumb, if there is little Gd in the body (eg 1 lifetime GBCA injection) and the most prominent GDD symptom is bone pain, intervals between chelation should be 4 weeks, to allow sufficient re-equilibration (that is Gd moving out of bone on its own). In the process some sizable amount of that Gd is eliminated through the kidneys, but probably in the range of 50% gets redistributed to soft tissues, where chelation can remove Gd much more efficiently. This approach is the best method to reduce total body Gd content. In contrast if you have received a lot of Gd (eg > 10 GBCA injections) and bone is not the dominant symptoms, but cognitive impairment is, then too much re-equilibration will be a problem, so a shorter interval (eg 1 week) is preferred. This is ofcourse the extremes, and there is tremendous nuance to this. That is why expertize on the part of the chelating center is critical.

The route of toxin entry into the body is also critical to understand, at least for the first few rounds of removal. Gd essentially uniquely of the major heavy metal toxicities has been acquired through iv administration, and at a fast rate. So initial treatment should also follow that pathway. So ideally, even in the setting of availability of effective oral chelators, optimal treatment would involve at least the first 3 removal sessions being with iv effective chelator and administered at a fast rate, In the untreated setting likely 90- 95% of Gd is deposited in a pericapillary, perivenular location, so chelation must be carried out to capture that deposition pattern. With re-equilibration the dominance of this location is diminished, so oral chelator can be substituted in. This will be optimal Gd removal for the future. In contrast a metal like lead will have been acquired largely by oral route, so for pure lead Deposition DIsease, chelation regimen being solely by oral administration would be sufficient.

So yes, stirring up of Gd does occur with Gd removal, but this process can be used to important beneficial effect if done wisely.

Richard Semelka, MD