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MGH team develops a potential alternative to gadolinium-based contrast agents

by Lauren Dubinsky, Senior Reporter | November 21, 2017
Molecular Imaging MRI
Made of the vital element manganese
A team at Massachusetts General Hospital developed an MR imaging agent that may be used as an alternative to gadolinium-based contrast agents.

In recent years there have been concerns over the health risks associated with gadolinium for certain patients, and the industry has been searching for safer options.

"There is a clear clinical need for gadolinium-free MR contrast agents," Peter Caravan, co-director of the Institute for Innovation in Imaging at MGH, told HCB News. "This is most apparent for patients with renal impairment, for whom GBCAs pose the risk of potentially devastating nephrogenic systemic fibrosis."
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Caravan and his team developed a manganese-based agent called Mn-PyC3A. It can produce an MR signal comparable to that of GBCAs, and manganese is an essential element that the human body requires in small amounts.

The body naturally excretes excess manganese, but any gadolinium that is released from GBCAs is likely be retained in the body indefinitely. Studies have shown that it remains in the brain years after it was administered to the patient.

"The challenge with using manganese is being able to bind it tightly so that it is not released in the body, and to do this in a way that the strong MR signal remains," said Caravan. "Mn-PyC3A meets these requirements. Mn-PyC3A doesn't bind or interact with proteins or enzymes in the body, suggesting that its risk of causing adverse side effects is lower."

The team previously conducted mouse experiments and found that Mn-PyC3A provided good enhancement of blood vessels, liver and kidneys, and over 99 percent was excreted from the body within 24 hours by the liver and kidney.

In a more recent study published in Radiology, they compared the use of Mn-PyC3A to a commonly used GBCA in a baboon model. Each animal underwent two MR exams — one with Mn-PyC3A and one with the GBCA.

Once again, they found that the kidney and liver quickly excreted Mn-PyC3A and there was no evidence of the release of free manganese.

"Our MR contrast agent could replace GBCAs," said Caravan. "Mn-PyC3A was designed as a direct substitute for GBCAs, providing the same imaging results as GBCAs when used for the same disease indications. There are a number of studies that are needed for this replacement to happen."

They need to follow the FDA-mandated path to regulatory approval, which includes completing pre-clinical safety studies. Then they need to show in clinical trials that Mn-PyC3A is safe and provides the requisite diagnostic information.

"Once radiologists and referring physicians have experience showing that Mn-PyC3A provides the same diagnostic information as GBCAs and is safe to use, we think there will be widespread adoption of Mn-PyC3A," said Caravan.

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