Manganese liver contrast medium helps to cut MR examination times

March 29, 2010

CMC-001, an investigational MRI liver contrast medium, may be at least a partial answer to reducing the long imaging times.

CMC-001, an investigational MRI liver contrast medium, may be at least a partial answer to reducing the long imaging times that have frustrated patients and encouraged radiologists to look for imaging alternatives to aid diagnosis of hepatocellular carcinoma and colon cancer metastases in the liver. A phase III trial indicates it is as sensitive as gadoliniumenhanced MRI for detecting colon cancer metastases, but at the cost of lower specificity.

The current routine for imaging enhanced with MultiHance, Primovist, or Eovist, all gadolinium-based agents, has involved T1-weighted noncontrast imaging, then contrast administration, followed by a tedious 20 to 130-min wait to assure contrast uptake in the functioning hepatocellular tissue and optimal depiction of any lesions.

CMC-001, an oral manganese-based agent, promises to reduce procedure time to 10 minutes. Dr. Torkel B. Brismar, an associate professor of radiology at the Karolinska Institute in Stockholm, presented phase III trial results at the 2009 RSNA meeting that produced a mixed message in a comparison with MultiHance.

He performed a five-phase imaging protocol involving native, arterioportal, and portovenous imaging at five minutes and two hours on 20 patients with suspected liver metastases using MultiHance. Only the T1 and T2 postcontrast series were considered for CMC-001.

The sensitivities of the two agents were similar. Of 44 lesions verified with histopathology, 41 were detected during imaging enhanced with CMC-001, making it 93% sensitive to cancerous lesions compared with 42 observed with imaging enhanced with MultiHance for a 95% sensitivity. The sensitivity of noncontrast MRI was 64%.

However, the equivalent sensitivity for CMC-001 was bought at the expense of lower specificity, Brismar said. Imaging with the agent produced 15 false positives compared with only two false positives for MultiHance. The CMC-001 false positives included four miscategorized hemangiomas, two blood vessels, two fibrous lesions, two incidences of dysfunction, and one misidentified aneurysm clip. He reasoned that in a clinical situation, some of those should be possible to avoid if there are previous examinations available for comparison.

The big advantage for CMC-001 was measured in imaging time. Scans with the investigational agent were completed in 10 minutes. Imaging enhanced with MultiHance required 60 + 10 minutes.

Still, the performance was strong enough for Brismar to conclude that CMC-001 has good potential for use in colorectal liver metastasis screening.

According to session moderator Dr. Donald Mitchell, a professor of radiology at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania, the agent appears to dramatically improve contrast for liver and lesions during T1-weighted imaging because it is selectively delivered to the liver and excluded from other tissues. This behavior increases the likelihood of a high safety profile and reduces the probability for extrahepatic tissue enhancement, he said.

Mitchell cautioned, however, that CMC-001 will not take the place of standard gadolinium agents for liver imaging.

"There is no dynamic phase. It doesn't improve the visibility of vessels, so it is a more limited exam," he said.

Furthermore, questions about the agent’s cost have not yet been answered, he said. Its price may have a big effect on its future popularity.

"If it is not overpriced, then doing double contrast by combining it with a gadolinium chelate might produce a powerful examination," he said.