Breast cancer diagnosis pill to outperform mammograms?

Researchers at the University of Michigan (UM) are developing a pill that makes tumours light up when exposed to infrared light, and they have demonstrated that the concept works in mice.

About a third of breast cancer patients treated with surgery or chemotherapy have tumours that are benign or so slow-growing that they would never have become life-threatening, according to a study from Denmark in 2017. In other women, dense breast tissue hides the presence of lumps and results in deaths from treatable cancers. If we use molecular imaging, we can see which tumours need to be treated, said Greg Thurber, UM assistant professor of chemical engineering and biomedical engineering, who led the team.

Thurber's team uses a dye that responds to infrared light to tag a molecule commonly found on tumour cells, in the blood vessels that feed tumours and in inflamed tissue. By providing specific information on the types of molecules on the surface of the tumour cells, physicians can better distinguish a malignant cancer from a benign tumour.

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 tumour. 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.

But it's not easy to design a pill that can carry the dye to the tumour. "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," Thurber said.

Fortunately, they weren't the only people looking for a molecule that could get from the digestive system to a tumour. 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," Thurber said. "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 tumours light up.

The research is described in a study 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 at the U-M College of Pharmacy. It was supported by the Foundation for Studying and Combating Cancer and the National Institutes of Health.

Image caption: Sumit Bhatnagar, a PhD student in chemical engineering, maintains samples of cancerous cells for use in the development of a pill that could help screen for breast cancer. Tumours are targeted by a molecule that carries a fluorescent imaging agent in order to make earlier and more accurate breast cancer diagnoses. Image credit: Evan Dougherty/Michigan Engineering Communications & Marketing.