MRI agent distinguishes aggressive from slow-growing breast cancer

Researchers have tested a  new magnetic resonance imaging (MRI) contrast agent that not only pinpoints breast cancers at early stages but differentiates between aggressive and slow-growing types.

“Doing both will help doctors find the right treatment,” said Zheng-Rong Lu, the M. Frank Rudy and Margaret Dormiter Rudy Professor of Biomedical Engineering at Case Western Reserve and leader of the research. “There’s no such technology available now that we know of.”

The gadolinium-based agent is also more efficient and safer than traditional agents, requiring a gadolinium dose 20-times smaller, easily flushing from the body and leaving no accumulation in tissues, the researchers found in tests with mouse models.

At the low dosage, the agent lights up cancer biomarkers during scans, overcoming the low sensitivity of MRI’s for imaging the markers.

To make the agent, Dr Lu and colleagues at Case Western Reserve combined commercially available tri-gadolinium nitride metallofullerene (Gd3N@C80), a highly efficient contrast agent, with a peptide labelled ZD2, which was developed in Dr Lu’s lab.

Compared to the gadolinium used in traditional agents, Gd3N@C80’s “structure is different–the gadolinium ions are encaged in a hollow molecule of fullerene that looks like a soccer ball,” Dr Lu said. “The cage prevents direct contact between the gadolinium and tissue, and the gadolinium will not be released, which prevents any kind of interaction with tissue.”

The lab applies ZD2 to the surface of the soccer ball. The peptide specifically targets the cancer protein extradomain-B fibronectin (EDB-FN). EDB-FN, which is associated with tumour invasion, metastasis and drug resistance, is highly expressed in the matrix around cancerous cells in many aggressive forms of human cancers.

In testing on six mouse models, MRI’s detected breast cancers in all cases. But the signal created by the accumulation of contrast molecules on three aggressive triple-negative breast cancers (MDA-MB-231, Hs578T and BT549) were significantly brighter. Because slow-moving ER-positive breast cancers (MCF-7, ZR-75-1 and T47D) produce less EDB-FN, fewer molecules attached. While detectable, the signal was muted.

Dr Lu’s lab is now investigating ways to reduce the cost of producing the agent to make it more attractive for clinical use. The research has been published t in Nature Communications.