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AN-DTPA: What is it? It is not Ca-/Zn-DTPA.

I was notified by a couple of close collaborators in the GDD sufferer community that a great panic has arisen because AN-DTPA was uncovered on Drugs.com and horrible side effects were described, and therefore was Ca-/Zn-DTPA also dangerous.

This reveals at its core one of the issues I have faced in dealing with panics by non-experts about everything. Starting with, from my colleagues in Radiology and the formal medical community, GDD does not exist, GBCAs are perfectly safe.... and for me to say there are issues with GBCAs it is like setting the Congress or Reichstag on fire and destroying everything. My writing on GDD is ruining everything that is good in life, is the opinion of some.

AN-DTPA is Tc 99m - DTPA which is a nuclear medicine agent used for a number of purposes, but primarily now for nuclear renal scans. As I have described in earlier emails DTPA is used as the ligand for a number of molecules because of its inherent safety and stability with many cations, especially heavy metals (like Gd, Technetium, Selenium, and Plutonium). There are often side branches added on to DTPA to achieve various purposes usually stability or enhanced activity of what it is being used for..

Now I am not intending to defend AN-DTPA in particular, but generally speaking if you read the side effects of any drug, they almost all sound horrific. So you just need to watch TV and see the advertisements for DMARDS used for Crohn's, Psoriasis, atopic dermatitis, Humira, Stelara, Cosentyx etc.... These all describe severe infection such as TB and fatal cancers, and a variety of horrible fatal autoimmune conditions. So a very critical consideration that we all need in advance of taking medications, is how likely are various serious side effects. And Weigh this against the benefit of taking the drug.

So AN-DTPA is a different chemical than Ca-/Zn-DTPA, and what is interesting, is among the side effects they describe is metal taste.. which would not be expected from DTPA on its own... but would be expected from Tc, as we observe it for Gd. So my current opinion is that the side effects described are actually Tc-Deposition Disease (Tc-DD). In reading earlier blogs of mine I have described lead toxicity as actually Pb-DD, as essentially all of us have Pb- Storage Condition, and only a small percentage true Pb-DD, also true for other heavy metals- mercury chromium, etc.

Looking at all medical uses of DTPA there have been perhaps 500-700 million doses of DTPA. 300 million as MR GBCAs (Magnevist and Omniscan) maybe 100 million for a full range of nuclear medicine tests, then for many other medical applications. So any specific toxicity for DTPA would be much lower than for ligands not used for these purposes... But we do know that Magnevist and Omniscan can cause NSF, GDD, and Acute Hypersensitivity reaction- but all relatively rare ( 1 in 10,000 mild, 1 in 100,000 severe). It is therefore reasonable to think the same would be true for other metals like Tc and Selenium, they would cause analogous conditions... But the toxicity is related to the cation (a toxic metal) and not the ligand (the safe part of the molecule).

Is DTPA 100% safe.... well what we know from everything in medicine, nothing is 100% safe - nothing. It is as safe or safer than almost everything else done in medicine - but that is not 100% It certainly would be many levels safer than alternative chelating agents - otherwise the Tc we use in Nuc Med would be Tc-EDTA or the MR agents would be Gd-EDTA... But they are not because these are much more likely to be toxic, maybe by atleast 1000 fold.

So the toxicity of AN-DTPA is primarily the toxicity of Tc, just like the MR contrast agents the toxicity is related to Gd. And the toxicity of Tc is like Gd, which is itself like other heavy metals like Pb.

If you feel the need to be put into a panic by imaging, read up on the mechanism of image generation from FDG-PET.... now that scares even me. Or read the radiation doses of the full range of nuclear medicine studies and the risk of cancer development - look at Gallium scanning for example. Many patients reach out to me and ask if they should get some imaging study that they are sent for, and I generally tell them, I can tell you what I would do (and I known an enormous amount about imaging), and you can then decide for yourself. Most of the time I tell them I would not undergo that.

I do recognize that GDD sufferers have had to do all the research on their own, since generally their medical providers, and actually organized medicine in general, have ignored them. So some issues that come to light from the community that seem very important I will try to address.

I am doing more research into this AN-DTPA, and consulting with experts in molecular pharmacy, if I learn more that is important I will write a follow-up blog.

Is DTPA perfect for GDD, no, but it is better by far than anything else we have available. HOPO may well be better, but we do not have it available yet. And I would prefer BOPTA as an MR ligand to use as a Gd chelator than DTPA, but it is not available either. We are living in the now, and have to do the very best we can with what we have available.

Richard Semelka, MD