MRI Technique Spots Small, Aggressive Breast Cancers

This post was originally published on this site

Researchers at Case Western Reserve University have found that a new contrast agent used in combination with magnetic resonance imaging (MRI) can pinpoint breast cancers at early stages, and even differentiate between aggressive and slow-growing types.

“Doing both will help doctors find the right treatment,” said study leader Zheng-Rong Lu. “There’s no such technology available now that we know of.”

The new contrast agent is based on gadolinium, a form of rare-earth mineral that requires a dose 20 times smaller than traditional iodinated agents and is easily flushed from the body, leaving no residue to accumulate in tissues.

Using a low dosage, the agent lights up cancer biomarkers during scans much better than traditional MRI contrasting agents, overcoming the difficulty of MRIs in spotting cancers.

To make the agent, Lu and colleagues combined commercially available tri-gadolinium nitride metallofullerene ([email protected]), a highly efficient contrast agent, with a peptide labeled ZD2, which was developed in Lu’s lab.

The structure of [email protected] is different: “The gadolinium ions are encaged in a hollow molecule of fullerene that looks like a soccer ball,” 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.”

But what makes the new technique different is the peptide. Researchers apply ZD2 to the surface of the soccer ball, which specifically targets the cancer protein extradomain-B fibronectin (EDB-FN).

EDB-FN, which is associated with tumor invasion, metastasis and drug resistance, is found in high amounts 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 detectible, the signal was muted.

The research was published in Nature Communications.

Last year, researchers at the University of Michigan developed a pill containing a fluorescent dye which attaches to cancerous tissue and fluoresces under a near infra-red light. They believe that pairing an instrument that detects near infra-red light with ultrasound should accurately detect most breast cancers. The technique should also be effective for diagnosing women with dense breast tissue whose mammograms are difficult to read. 

About 12 percent of American women will develop breast cancer during their lifetime. In 2016, 246,660 new cases of invasive cancer are projected to be diagnosed, along with 61,000 new cases of non-invasive (in situ) breast cancer. Over 40,000 American women die from the disease each year.