Scientists help develop probe to identify cancer cells more efficiently

Duke scientists have helped make it easier to detect cancer cells by using a probe that makes the cells more visible.

Sarcoma, a form of cancer that involves the connective tissues of the body, is often treated with the complete removal of the cancerous tumor. Researchers from Duke, the Massachusetts Institute of Technology and Massachusetts General Hospital recently developed a probe that can locate and stick to cells embedded in healthy tissue, then cause the cells to light up to make them easier to locate. The probe, called LUM015, is described in a study recently published in Science Translational Medicine in which surgeons used the probe safely to identify and remove tumors in mice and people.

“This study was a phase I study of the fluorescent probe in humans. It was the first use of an activated fluorescent probe in humans,” said Dr. Brian Brigman, orthopaedic cancer surgeon, associate professor of orthopaedic surgery and pediatrics, head of the Duke sarcoma program and an author of the study. “It was primarily testing the safety of the probe in humans and the ability to visualize tumors.”

The study involved a trial that featured 15 patients—12 with soft tissue sarcoma and three with breast cancer—as well as mice with soft tissue sarcoma. Researchers inserted the probe—which after attaching to its target breaks down and releases a fluorescent agent that makes the cells brighter and easier to see—where tumors had been removed from the people and mice. They determined that the method was safe and could be effective in finding cancer.

For sarcoma patients, the high recurrence of symptoms in patients treated with surgery alone means many patients are also treated with radiation, which is expensive and has its own complications, Brigman explained. LUM015 could help this situation for patients by making it easier to determine whether tumors are present in the patient after surgery.

David Kirsch, professor of radiation oncology, pharmacology and cancer biology and an author of the study, noted that although many patients benefit from radiation therapy after primary treatment, some patients have no residual cancer and would not benefit from the adjuvant treatment.

The use of the new fluorescent imaging agent circumvents the potentially toxic effects of radiation treatment and is novel in its employment of human subjects, Kirsch explained.

“One of the most challenging parts of this study was enrolling patients into a clinical trial of a new imaging agent that had been tested in mice, rats, and canine patients with cancer, but had never before been given to a person,” he said.

Melodi Javid Whitley, an MD/Ph.D. student in the department of pharmacology and cancer biology who wrote the clinical trial protocol and conducted imaging on the tissues, said she expects LUM015 to be a versatile new tool for cancer treatment.

“It is likely that it will also work in other types of cancer like ovarian cancer, prostate cancer,” Whitley said. “I am particularly interested in seeing if it can help dermatologists remove skin cancer and melanoma.”

In future studies, the researchers will aim to determine if techniques involving fluorescent probes such as LUM015 can indicate whether an entire tumor has been removed. For example, LUM015 might prove effective in allowing for less radiation or direct radiation that only targets the tumorous region.

“Currently, there is a group of people at Mass General Hospital in Boston to test this further with patients who have breast cancer,” Whitley noted. “Instead of just looking at the tissues that came out of the patient, they will use cameras to look inside the patient.”