New technique spots tiny metastases to detect high-risk breast cancer

Researchers have shown that magnetic resonance imaging (MRI) on the molecular level, combined with a novel contrast agent, can detect the earliest signs of high-risk breast cancer and metastasis in a mouse model. Human testing may only be a few years away, they predicted.

The researchers were able to identify micrometastases—tiny cancers less than 2 mm, which can’t be seen with current imaging modalities. Their results were published in an online article in the August 12, 2015 issue of Nature Communications.

“We showed with this technique that we can detect very tiny tumors of just a few hundred cells,” said study leader Zheng-Rong Lu, PhD, professor of biomedical engineering and an expert in molecular imaging for cancer and other diseases at Case Western Reserve University (CWRU), in Cleveland, OH. “Our imaging technology has the potential to differentiate aggressive tumors from low-risk tumors. These are two things that potentially can make a big impact on clinical practice and also management of cancer.”

The investigators took advantage of fibronectin, a glycoprotein that is expressed in high-risk, aggressive cancer but not in normal tissue. In previous work, they had developed a novel penta-peptide contrast agent, CREKA-Tris(Gd-DOTA)₃, which binds to fibrin-fibronectin complexes that are abundant in the tumor microenvironment of fast-growing breast cancer.

For this study, the researchers tested their approach in mice implanted with metastatic breast cancer. Two weeks after they introduced cancer cells in the mice, the researchers injected their contrast solution and performed molecular imaging.

They found that molecular MRI detected metastatic tumors, including micrometastases, in lung, liver, lymph node, adrenal gland, bone, and brains of the mice. In analyzing their images, they determined that the contrast agent bound almost exclusively to the fibrin-fibronectin complexes, producing a strong and prolonged image enhancement of micrometastases and tumors. They confirmed their findings using cryo-imaging, which verified that the MRI technique could detect micrometastases even smaller than 0.5 mm.

“The recurrence rates of some forms of breast cancer and the consequence of metastatic cancer make these efforts urgent and important,” Dr. Lu said, adding that he and his colleagues hope to use their method to detect prostate cancer as well. “We think this targeted approach holds great promise for earlier imaging of high-risk cancers in the clinic. It could also become useful as a non-invasive way to assess breast cancer treatment progress.”

Next, the researchers plan to confirm the safety of their novel contrast agent. Then they hope to pursue human clinical trials using this approach.