A new magnetic resonance imaging (MRI) contrast agent finds breast cancers at early stages and differentiates between aggressive and slow-growing types. The work comes from researchers at Case Western Reserve University and was published today in Nature Communications.
According to the team, the gadolinium-based agent is more efficient and safer than traditional agents. At a low dosage, the agent lights up cancer biomarkers during scans, overcoming the low sensitivity of MRI's for imaging the markers. The researchers led by Zheng-Rong Lu, Ph.D., the M. Frank Rudy and Margaret Dormiter Rudy Professor of Biomedical Engineering at Case Western Reserve, combined commercially available tri-gadolinium nitride metallofullerene (Gd3N@C80) and a peptide labeled with ZD2.
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," 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 the key technology for our targeted contrast agent is the peptide attached," Lu said.
The ZD2 peptide is applied to the surface of the soccer ball and specifically targets the cancer protein extradomain-B fibronectin (EDB-FN). EDB-FN, which is associated with tumor invasion, metastasis and drug resistance, is highly expressed in the matrix around cancerous cells in many aggressive forms of human cancers. In six different mouse models, the researchers detected breast cancers in all cases.
Lu's lab is now investigating ways to reduce the cost of producing the agent to make it more attractive for clinical use.
Image: The figure shows the different expression of the biomarker (EDB-FN) and probe binding (ZD2) in slow-growing ER-positive breast cancer (not much yellow and red color representing low expression of the biomarker and low binding), and in triple- negative breast cancer (TNBC, high expression and high binding). As a result, the targeted contrast agent produced weak signal enhancement (brightness) in the former and strong signal (brightness) in the latter as pointed by the arrow. The technology is able to provide accurate detection and risk-stratification of aggressive BC. Image courtesy of Case Western Reserve University.