WVU receives nearly $2.2 million to study MRI contrast agent for breast cancer

Margaret Bennewitz, associate professor of biomedical engineering, works with a student in her lab. (WVU Photo/Paige Nesbit)

Early detection, access to screenings and new treatments have been critical to improving outcomes for patients with breast cancer. Researchers at West Virginia University hope to build on that foundation by enhancing MRI contrasts to more precisely pinpoint the cancer, which could lower the rate of unnecessary mastectomies while preserving healthy tissue.

Story by WVU School of Medicine News 
Photos by Paige Nesbit 

Benjamin M. Statler College of Engineering and Mineral Resources

With support of a $2.195 million National Cancer Institute (NCI) R01 grant, researchers will focus on developing an improved MRI contrast agent. The work expands their research on Nano-Encapsulated Manganese Oxide (NEMO) particles, a new contrast agent specifically designed to locate tumor cells more precisely than contrast agents currently used in the clinic.

“Our main goal is to be able to get a better imaging agent that can tell us what is actually tumor so that we can promote more conserving surgeries to remove less breast tissue for the person,” said Margaret “Maggie” Bennewitz, Ph.D., associate professor of biomedical engineering at the Statler College of Engineering and Mineral Resources, who leads the study. “If you have an overestimation of cancer, the surgeon is going to be more conservative and remove more breast tissue than what you need. From our research, patients tend to have more mastectomies, or complete removal of the breast tissue, because it seems like there’s more tumor left than there actually is.”

The research team includes Tim Eubank, Ph.D., Moriah Katt, Ph.D., Tracy Liu, Ph.D., Trieu Nguyen, Ph.D., Sijin Wen Ph.D., Dr. Shubha Dave, Dr. Sarah Palko and Dr. Danish Safi from WVU School of Medicine, the WVU Cancer Institute, and WVU Health Sciences, bringing unique insights and knowledge to the research.

The study involves combating nonspecific MRI contrast agents by developing particles that include a tumor-targeting peptide that binds to cancer cells. When the cancer cells absorb the particles, they are shuttled into low pH endosomes and lysosomes. The low pH in the sacs causes the NEMO particles to release manganese oxide, turning on the MRI signal.

While an MRI is the best imaging tool for detection of breast cancer following chemotherapy, the agent currently used in the clinic may give a positive signal immediately upon injection, leading to higher rates of immune cells and accumulating scar tissue showing up as cancer positive. The NEMO contrast won’t appear on the MRI until they get inside cancer cells.

To conduct the study, the team will use MRI and fluorescence live-animal imaging to compare how well they detect tumors in mice and how well they respond to treatment.

“Think of it as a light bulb that is always on,” Bennewitz said. “As soon as you inject it, it’s giving you a signal in the blood vessels and basically in any tissue that has blood vessels, so it can light up normal tissue and cancerous tissue.”

Bennewitz hopes that if the study produces successful data, it could lead to later testing on larger animal models.

The five-year R01 grant is considered a career milestone for investigators in the biomedical sciences, cancer and biomedical engineering fields. Bennewitz has been working on this research program for roughly eight years, and she believes the contrast agent has the potential to be effective for up to 90 percent of cancer forms.

As part of the grant, Bennewitz is pioneering the use of microfluidic MRI of organ-on-a-chip models to enable high throughput contrast agent testing under dynamic flow conditions. This technology has the potential to reduce reliance on animal studies while advancing NIH’s and Federal Drug Administration’s vision for next generation organ-on-a-chip systems. For patients, that could mean conservation of more breast tissue and enhanced quality of life.

“Clinicians and basic scientists bring complementary perspectives to the problem,” Eubank said. “You really want to understand the complexity of the system before you can address it in a way that provides the greatest benefit. This grant brings together imaging, physics, biochemistry, immunology and a clinical perspective. It’s a truly multidisciplinary project, and understanding the problem from all of those angles is what will make it successful.”

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