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Part 2 of 2 Parts (Please read Part 1 first)
     There is not sufficient scientific evidence at this time to definitively establish a link between gadolinium retention and adverse side effects. Abergel hopes to be able to develop such evidence. She said, "With funding from generous supporters through the Berkeley Lab Foundation, we were able to establish The Marcie Jacobs Fund for Gadolinium Toxicity Research and start investigating how gadolinium interacts with biological molecules and organs. What does gadolinium do that would result in toxicity and observable symptoms in patients?"
     The anti-radiation-poisoning pill developed by Abergel’s team was approved for in-human Phase I safety trials in 2014. The chelator is a hydroxypyridinone ligand (HOPO) which is well suited to be administered in a pill. It is non-toxic when administered in the doses used in therapy and diagnosis. Not only does it selectively remove plutonium and other heavy, radioactive elements but it is also highly selective in the removal of the lanthanide series including gadolinium. Abergel said, “So, we thought that we should investigate whether this HOPO chelator could remove gadolinium deposits from MRI patients after the contrast agent has done its job.”
    Abergel reported on her research in the Nature online publication Scientific Reports. They used animal models to show that, compared to conventional chelators such as diethylenetriamine pentaacetic acid (DTPA), their HOPO chelator is many times more effective for the removal of gadolinium following an MRI. Abergel said, “We also found that if we give the drug right before or right after the MRI, we can prevent up to 96% of the gadolinium from depositing.”
     The research also revealed that the HOPO chelator is more selective for gadolinium than DTPA. Unfortunately, DTPA also binds to and removes important minerals from the body including calcium and zinc. Abergel and her team are now working on identifying which populations of patients are most vulnerable to gadolinium poisoning. Abergel said, “What would affect larger or smaller gadolinium retention and where does it end up? It depends on how fast you can clear it out, and how well your kidneys function.”
     Abergel said in her report that to date, the development of her HOPO chelator has been supported by federal agencies such as the National Institutes of Health and the Biomedical Advanced Research and Development Authority. Now she and her team are seeking other funding sources for their research in order for them to fund a first clinical safety study to develop the drug into a gadolinium removal agent.
     The work of Abergels team on chelators builds on the landmark projects that were carried out thirty five years ago by Kenneth Raymonds, a member of the Berkley Lab faculty and chemistry professor at the University of California, Berkley. Raymond worked closely with a biophysicist at Berkley Lab named Durbin-Heavy. Together they tested a great number of new chelating compounds for the removal of heavy metals such as plutonium from the human body.
     Abergel said, “This is the kind of research that could only take place in a national lab setting. Here at Berkeley Lab we have access to research facilities that allow us to do this work in a well-controlled, well-implemented, and safe environment. It would be difficult to find all of these capabilities in one place anywhere else.”