Findings in mice show pill for breast cancer diagnosis may outperform mammograms A new kind of imaging could distinguish aggressive tumors from benign, preventing unnecessary breast cancer treatments.

As many as one in three women treated for breast cancer undergo unnecessary procedures, but a new method for diagnosing it could do a better job distinguishing between benign and aggressive tumors. Researchers at the University of Michigan are developing a pill that makes tumors light up when exposed to infrared light, and they have demonstrated that the concept works in mice.

Mammography is an imprecise tool. About a third of breast cancer patients treated with surgery or chemotherapy have tumors that are benign or so slow-growing that they would never have become life-threatening, according to a study out of Denmark last year. In other women, dense breast tissue hides the presence of lumps and results in deaths from treatable cancers. All that, and mammograms are notoriously uncomfortable.

“We overspend $4 billion per year on the diagnosis and treatment of cancers that women would never die from,” said Greg Thurber, an assistant professor of chemical engineering and biomedical engineering, who led the team. “If we go to molecular imaging, we can see which tumors need to be treated.”

The move could also catch cancers that would have gone undetected. Thurber’s team uses a dye that responds to infrared light to tag a molecule commonly found on tumor cells, in the blood vessels that feed tumors and in inflamed tissue. By providing specific information on the types of molecules on the surface of the tumor cells, physicians can better distinguish a malignant cancer from a benign tumor.

Compared to visible light, infrared light penetrates the body easily—it can get to all depths of the breast without an X-ray’s tiny risk of disrupting DNA and seeding a new tumor. Using a dye delivered orally rather than directly into a vein also improves the safety of screening, as a few patients in 10,000 can have severe reactions to intravenous dyes. These small risks turn out to be significant when tens of millions of women are screened every year in the US alone.

But it’s not easy to design a pill that can carry the dye to the tumor.

“To get a molecule absorbed into the bloodstream, it needs to be small and greasy. But an imaging agent needs to be larger and water-soluble. So you need exact opposite properties,” said Thurber.

Fortunately, they weren’t the only people looking for a molecule that could get from the digestive system to a tumor. The pharmaceutical company Merck was working on a new treatment for cancer and related diseases. They got as far as phase II clinical trials demonstrating its safety, but unfortunately, it wasn’t effective.

“It’s actually based on a failed drug,” said Thurber. “It binds to the target, but it doesn’t do anything, which makes it perfect for imaging.”

The targeting molecule has already been shown to make it through the stomach unscathed, and the liver also gives it a pass, so it can travel through the bloodstream. The team attached a molecule that fluoresces when it is struck with infrared light to this drug. Then, they gave the drug to mice that had breast cancer, and they saw the tumors light up.

“It’s actually based on a failed drug. It binds to the target, but it doesn’t do anything, which makes it perfect for imaging.”Greg Thurber

The research is described in a paper in the journal Molecular Pharmaceutics, titled, “Oral administration and detection of a near-infrared molecular imaging agent in an orthotopic mouse model for breast cancer screening.”

This work was done in collaboration with David Smith, the John G. Wagner Collegiate Professor of Pharmaceutical Sciences in the College of Pharmacy, and a member of the Comprehensive Cancer Center.

The study was supported by the Foundation for Studying and Combating Cancer and the National Institutes of Health.

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Coating method could improve temporary implants that dissolve in the body

A strategy for coating complicated surfaces with biodegradable polymers has been pioneered by a team of researchers led by Joerg Lahann, a professor of chemical engineering and director of the Biointerfaces Institute at U-M. It could enable coatings for implants that dissolve in the body, such as drugs to improve healing.

Permanent polymer coatings are already used on medical equipment that does not biodegrade, such as metal stents that hold blocked arteries open. The drug prevents cells from growing over the webbed metal structure and narrowing the artery again. It can be applied with a technique called chemical vapor deposition – a process that puts the drug into a gas phase and lays it down in an even coating, like fog turning into frost.

“What you couldn’t do until we published this paper is take a suture that biodegrades and coat with a vapor-based coating that would provide similar benefits,” said Lahann. A suture or a biodegradable bone screw might benefit from a coating of growth factors to promote healing, he added.

Other ways of coating include dissolving the drug into a solvent and then spraying it onto the structure. However, the solvents are often toxic, and the spray technique can bridge gaps in open structures or result in one part of a structure blocking the spray from reaching another.

Still, chemical vapor deposition is very tricky with polymers, or chemicals built in a chain – and a biodegradable coating would need to be made out of polymers. Polymers tend to break up when they are vaporized, so they must be built piece by piece onto a surface.

The researchers demonstrated this using two different monomers, or types of links in the polymer chain. By controlling the ratio between the two monomers, and the chemical groups hanging off the sides of the monomers, the team could control how quickly water could get into the polymer and begin breaking up the chain into its nontoxic elements.

In the lab, Lahann’s group is testing out the coating technique with biodegradable scaffolds that they use for implanting stem cells to help heal wounds involving gaps in tissue. They are also beginning a project with the lab of William Giannobile, the Najjar Professor of Dentistry and Biomedical Engineering, to coat biodegradable dental implants with growth factors to speed healing.

Other members of the research team hailed from Northwestern Polytechnical University in Xi’an, China, and the Karlsruhe Institute of Technology in Eggenstein-Leopoldshafen, Germany.

The study was funded the German Science Foundation under the SFB grant 1176 and the Army Research Office (ARO) under Grant W911NF-11-1-0251.

Lahann is also a professor of biomedical engineering, macromolecular science and engineering, and materials science and engineering.