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Redistribution and Redistribution Flare. The Unwanted Flare. How to Minimize.

Redistribution is the unwanted Flare reaction that I have described in multiple prior blogs. This blog focuses on it. The most important way to avoid Redistribution Flare is to use the strongest available chelator, which is described as log stability constant. The stability constant is the measure of how strong the bond is between the administered chelator and the metal in question, and this also varies in what speciation (what molecule the metal is bonded to) the metal is in. This especially applies to Mercury.

The strength of the bond between the chelator and Gd has been recognized for decades to be the crucial determiner for what chelate is optimal for a GBCA creation (or chelator to employ). But this is equally important in the setting of GDD, and not so appreciated, is that the greater stability is important for decorporation (removal from the body) for GBCAs in which some remains in the intact form. Probably all GBCAs there is some amount of Gd that remains intact in the original form (even Omniscan, Optimark, the least stable GBCAs) or likely the entirety of the Gd is in the intact GBCA form (Prohance, Dotarem/Clariscan). I have in the past hypothesized that DTPA may act as a carrier molecule to the kidneys and the excretory mechanism, but it may be the the chelator simply tugs the intact GBCA from the extracellular matrix back into the circulation, and the intact GBCA on its own is eliminated. The more powerful the chelator the greater the ability of the chelator to tug the agent back into circulation.

So the stability constant is critical for chelators, both when it transmetallates (exchange cations) for Gd retained in the body, but also when it tugs intact GBCA back into the circulation for removal.

My current empiric estimates for re-distribution is 1-5% with DTPA, > 30% for EDTA, > 50% for DMSA, likely atleast > 50% for DMPS. Unknown for OSR since there is no stability constant described with Gd. HOPO likely redistributes < 1%.

I do not recommend using a chelator for Gd unless the log stability constant is known. Redistribution > 10% is likely to cause more harm than benefit, since Gd will be redistributed from skin to brain in a clinically appreciable amount.

Richard Semelka, MD

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