HOPO and DTPA. Initial Thoughts on Comparisons and Regimen for HOPO.

DTPA is a straight cation exchanger: exchanges Ca or Zn with Gd, in whatever form Gd is bound to. However my opinion is that the stablest GBCAs, Dotarem and Prohance, remain fully intact, and basically DTPA (and presumably HOPO) tugs the intact agent back into circulation where most of it is then eliminated by the kidneys. How HOPO works I believe is by electrostatic attachment.

HOPO does remove Gd through the renal route. At this point in time I am not sure how much is removed by fecal route as the majority of Gd agents are eliminated almost exclusively by kidneys. The bowel is not supposed to directly eliminate anything, so it is a mystery how this may happen, if it does, with HOPO. I think it may be another medical knowledge breakthrough that dealing with Gd has created. Gd removal through the fecal route does occur via biliary elimination, but this should only occur with eovist/ primovist ( a large amount) and multihance (a smaller amount).

The Flare effects of chelation are as follows, and these apply to all chelations for all heavy metals:

Gd removal Flare, which is good, shows Gd is removed and that you have the disease.

Gd redistribution Flare occurs when Gd is picked up and dropped off right away. Happens to an unacceptably high level with weak chelators.

Gd re-equilibration Flare (on the basis of le Chateliere's principle) occurs as a result of Gd moving from more stable repository sites (bone) to less stable, where much of the Gd is removed from with chelation, skin and soft tissues. This is often the best way to remove Gd from bone - which is critical in order to decrease total body Gd. Also if Gd removal from bone is not facilitated the gradient of bone Gd content and soft tissue Gd content will be enormous when chelation is stopped, so re-equilibration Flare could be massive.

To manage Flare and to train the immune system to react less to Gd (immune tolerance) is concurrent use of steroids at times of increased Gd movement, especially in  Gd removal phase.

So these 3 forms of Gd movement occur with every chelator, including HOPO, I have worked out how to manage and maximize the benefit with DTPA, HOPO for me is a work in progress. 

Oral administration with HOPO allows for more constant (daily) administration of Gd which then allows for a smaller amount of constant removal and less impetus for Flare, yet Gd removal Flare should still occur. Very low dose methylprednisolone is likely required to manage this and also facilitate development of immune tolerance. Even though HOPO may be able to remove more Gd directly from bone, likely still it is considerably less than from soft tissues, so gaps in chelation are still needed to achieve substantial bone removal.

A similar type regimen for HOPO will be necessary as done with DTPA. Some steroid use during periods of maximal Gd removal, and gaps between multiday chelator administration to achieve sufficient bone removal of Gd.

Richard Semelka, MD