"About 40% of MRI procedures use a contrast agent to produce a signal that can detect cancers, diagnose aneurysms or arterial narrowing, or identify the area of a heart damaged by a heart attack," explained corresponding author Peter Caravan. "All current FDA-approved MR contrast agents contain gadolinium, which in 2006 was associated with a devastating condition called nephrogenic systemic fibrosis in patients with impaired kidney function."

Caravan and his colleague Eric Gale developed Mn-PyC3A based on two properties of manganese: its ability to produce an MR signal comparable to that of gadolinium-based contrast and the fact that that - in contrast to gadolinium - manganese is an essential element. Intake of small amounts of manganese is required for vital bodily functions and the body has natural mechanisms to process and excrete any excess.

Previous studies in mouse models showed that Mn-PyC3A was resistant to the release of manganese ions and provided good enhancement of blood vessels, liver and kidneys in MR images. For the current study, the researchers compared the use of Mn-PyC3A to Gd-DTPA, a commonly used gadolinium-based contrast agent, in a baboon model.

Each animal underwent two identical MR angiography sessions, one with Mn-PyC3A and one with Gd-DTPA. The researchers used the same dosages and imaging protocols as would be used for human patients. The enhanced images of major arteries, kidneys, livers and specific muscles produced by both agents were comparable. As seen in mice, Mn-PyC3A was quickly excreted though both kidney and liver clearance, and there was no evidence of the release of free manganese.

"While we did not test it here, we believe that having an alternative route of elimination through the liver will provide an efficient mechanism for elimination of Mn-PyC3A in patients with kidney disease and prevent any retention of the contrast agent in the body," said Gale. "Our next steps are to manufacture Mn-PyC3A on a larger scale and conduct additional preclinical safety studies before we can begin testing in human patients."