Fluorescent Probe IDs Cancerous Tissue in Clinical Trial

An imaging probe that fluoresces in the presence of a cancer-related enzyme has been used safely in humans.

Beyond increasing a surgeon's ability to locate and remove all of a tumor on the first attempt, the technology could also help detect residual cancers following treatment.

Cancer surgeons currently rely on cross-sectional imaging such as MRIs and CT scans to guide them as they remove tumors. Often some cancerous tissue around the tumor is undetected and remains in the patient, sometimes requiring a second surgery and radiation therapy.

The new imaging technology was developed by researchers at Duke University and the Massachusetts Institute of Technology (MIT), as well as MIT spinoff Lumicell Inc., which developed the injectable agent used in the study.

A trial at Duke University Medical Center in 15 patients undergoing surgery for soft-tissue sarcoma or breast cancer found that the injectable agent LUM015 identified cancerous tissue in human patients without adverse effects. Courtesy of Shawn Rocco/Duke Medicine.

A blue liquid called LUM015, the substance fluoresces in the presence of the protease cathepsin, which is secreted in higher amounts by cancerous cells than by healthy ones.

A trial at Duke University Medical Center involving 15 patients undergoing surgery for soft-tissue sarcoma or breast cancer found that LUM015 identified cancerous tissue in human patients without adverse effects.

"At the time of surgery, a pathologist can examine the tissue for cancer cells at the edge of the tumor using a microscope, but because of the size of cancer, it's impossible to review the entire surface during surgery," said Duke professor David Kirsch. "The goal is to give surgeons a practical and quick technology that allows them to scan the tumor bed during surgery to look for any residual fluorescence."

The Duke trial represents the first time a protease-activated imaging agent for cancer has been tested for safety in humans, Kirsch said.

In companion experiments in mice, LUM015 created fluorescence in tumor tissue that was on average five times brighter than in regular muscle.

The resulting signals are not visible to the naked eye and must be detected by a handheld imaging device with a sensitive camera, which Lumicell is also developing. In the operating room after a tumor is removed, surgeons would place the handheld imaging device on the cut surface, where it would alert them to areas with fluorescing cancer cells.

Researchers at Massachusetts General Hospital are evaluating the safety and efficacy of LUM015 and the Lumicell imaging device in a prospective study of 50 women with breast cancer. Afterward, Kirsch said, multiple institutions would likely evaluate whether the technology can decrease the number of patients needing subsequent operations following initial breast cancer removal.

Results were published in Science Translational Medicine (doi: 10.1126/scitranslmed.aad0293).