Is Mn-PyC3A a viable alternative to gadolinium-based contrast agents?

The use of gadolinium-based contrast agents (GBCAs) to diagnose abnormalities in MR images has become one of radiology’s hottest topics, and it even made national news after a recent lawsuit filed by Chuck Norris and his wife, Gena. While it is widely accepted that patients with renal insufficiency can be negatively affected by GBCAs, debates about their impact on patients with normal renal function have escalated.

According to a new study published in Radiology, a manganese-based contrast agent, manganese-N-picolyl-N,N’,N’-trans-1,2-cyclohexenediaminetriacetate (Mn-PyC3A), could be on its way to replacing GBCAs in some advanced imaging exams.

“Our imaging and pharmacokinetics data support the hypothesis that Mn-PyC3A is a potentially viable alternative to GBCAs,” wrote Peter Caravan, PhD, of the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital in Charlestown, Massachusetts, and colleagues. “The relaxivity of Mn-PyC3A is comparable to that of the commercially available GBCA Gd-DTPA, and MR angiography demonstrated that Mn-PyC3A performs comparably to Gd-DTPA for blood vessel imaging. Dynamic imaging of the abdomen revealed rapid blood clearance and mixed renal and hepatobiliary elimination of Mn-PyC3A.”

The authors performed MR angiography with both Mn-PyC3A and gadopentetate dimeglumine (Gd-DTPA) in female baboons, comparing the enhancement produced by both agents and other key data. Overall, they found that “both contrast agents produced strong intravascular contrast enhancement.”

Caravan et al. also noted that there is a precedent for “the safe and effective use of manganese-based contrast agents.”

“The contrast agent manganese dipyridoxyl diphosphate has an FDA indication for imaging liver lesions, although the product is discontinued,” they wrote. “Manganese dipyridoxyl diphosphate is dissociated on injection, releasing free manganese into the bloodstream that is then rapidly taken up by the liver, pancreas, and myocardium. The dipyridoxyl diphosphate chelator recovered from the urine is near completely stripped of manganese.”

There is still much research to be done, the authors concluded, but the results of their research do indicate that such future evaluation is a worthy endeavor. “In parallel, a detailed study of the preclinical safety of Mn-PyC3A is warranted to advance this compound to clinical evaluation,” they wrote.

More coverage of GBCAs can be found here and here.