Once Again, GBCAs Grabbed the Headlines

Once again, gadolinium-based contrast agents (GBCAs) made the news.

MRI Patients Flush Gadolinium Into San Francisco Bay”  C&EN Latest News by Jyllian Kemsley.

Environ. Sci.Technol. DOI: 10.1021/acs.est.5b04322

This time, it is the potential threat to the environment.

On the flip side, it is a good that the patients get rid of the toxic metals!

GBCAs have been associated with nephrogenic systemic fibrosis (NSF) in patients with renal insufficiency.  In 2007, the FDA requested Boxed Warning for all the FDA-approved GBCAs about the risk of developing NSF following exposure to a GBCA in patients with severe kidney impairment, including patients with acute kidney injury or severe chronic kidney disease with a glomerular filtration rate < 30 mL/min/1.73 m2.  In 2010, the FDA issued the update to the warning to recommend screening of patients prior to administration of a GBCA to identify those who are at high risk for NSF.  On July 27, 2015, the FDA issued an announcement that the agency is investigating the risks of brain deposits following repeated use of GBCAs for MRI, even in patients with normal kidney function.

A group of patients, The Lighthouse Project, has voiced the concerns and presented convincing evidences about the effects of gadolinium toxicity after contrast enhanced MRI procedures.

The threat of GBCAs is very scary!

Perhaps patient’s urine should be collected after the MRI.  This will keep gadolinium away from our environment and maybe someone will come up with the efficient way to recycle the metals.  A step further is the gadolinium urine test.  This will provide massive data about excretion of GBCAs, a peace of mind for patients, an opportunity for prompt treatment to avoid the consequent serious medical condition.  If the manufacturers are serious about GBCAs safety for all patients and our environments, they should pay.

No doubt, there is a need to develop a new class of contrast agents for MRI, an alternative to GBCAs.  How about metal-free, organic radical contrast agents (ORCAs)?  We have prepared an ORCA that has a long shelf‐life and provides enhanced MRI in mice for over 1 h (J. Am. Chem. Soc., 2012, 134, 15724–15727. DOI:10.1021/ja3079829; All-Organic MRI Contrast Agent Tested In Mice).

We have worked hard to secure funding to work on this project, to further optimize properties the ORCAs.  Our long-term goal is an ORCA that provides high quality in vivo MR images for clinical use.  From 2011, numerous grant applications— 7 or so (can’t remember exactly, too many) NIH R01, Keck Foundation—all failed!  Can anyone top this for the failed attempts?  We finally succeed in the 8th attempt with the NIH-R01 grant.  Exhausted but happy, thank you NIBIB and NIGMS.

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Posted in MRI, organic radical

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