Researchers at Case Western Reserve University have developed a magnetic resonance imaging (MRI) contrast agent that detects much smaller aggressive breast cancer tumors and micrometastases than current agents can identify.
“Currently, there is no imaging technology in clinical use that can detect tumors or metastases smaller than 2 millimeters in diameter,” said Zheng-Rong Lu, professor of biomedical engineering and leader of the research. “This can detect them as small as 300 microns—a few hundred cells.”
Metastasis is the most common cause of breast cancer deaths. Scientists believe early detection and treatment of primary and metastatic tumors increases the chances of survival.
The research is published in today’s Nature Communications. Lu spent a decade developing and testing imaging agents. He worked with Case Western Reserve University research associate Dr. Zhuxian Zhou, PhD students Mohammed Qutaish, Zheng Han, Rebecca Schur and Yiqiao Liu and fellow biomedical engineering professor David Wilson.
The key to earlier detection is a small peptide gadolinium-based MRI contrast agent that binds to molecular markers, called fibrin-fibronectin complexes. The complexes are expressed in high-risk primary tumors and metastases.
CLEVELAND—Researchers at Case Western Reserve University combined finely crafted nanoparticles with one of nature’s potent disrupters to prevent the spread of triple-negative breast cancer in mouse models.
The highly aggressive cancer subtype is difficult to manage and, currently, the FDA has no approved targeted treatments. But striking results from a new study, published in the journal Cancer Research make the researchers optimistic they have a potential game-changer for triple negative cancer and more.
To try to tackle metastasis, Schiemann teamed with Zheng-Rong Lu, the M. Frank and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve, Jenny Parvani, now a postdoctoral investigator, PhD student Maneesh Gujrati and undergraduate student Margaret Mack.
Lu’s lab has been developing lipid-based nanoparticles to deliver medicines to specific targets in the body for a decade. Lipids include fats and oils, but these organic molecules are also building blocks in cell structures and functions.
The study adds to growing evidence that a lack of β3 integrin stops production of migrating cancer cells.
In this study, five mice with a mouse version of triple-negative breast cancer were injected with particles every five days for 14 weeks. Compared to control mice, the treated mice’s tumors shrunk significantly, but more importantly, the treatment significantly inhibited metastasis.
Five mice with human triple-negative breast cancer received the same treatment, which produced the same results.
“The results were really, really surprising,” Lu said.
“I was shocked, actually,” Schiemann said. “We can do most anything invitro in the lab, but to do this in the live body of a mouse is a huge hurdle to clear.”
Four weeks after treatment was stopped, the treated mice remained tumor free while cancer continued to grow in untreated controls.
“We’re also looking at different genes, different therapies and more delivery platforms,” Lu said....