A new injectable agent causes cancer cells in a tumor to fluoresce, potentially enabling surgeons to locate and remove all of a cancerous tumor on the first attempt. The injectable was used in a trial with 15 patients undergoing surgery for soft-tissue sarcoma or breast cancer in which the injectable agent identified cancerous tissue in human patients without adverse effects, according to findings published in Science Translational Medicine (doi:10.1126/scitranslmed.aad0293).
The imaging technology was developed through a collaboration with scientists at Duke University Medical Center in Durham, North Carolina, the Massachusetts Institute of Technology (MIT) in Boston, and Lumicell Inc in Wellesley, Massachusetts.
Currently, surgeons use cross-sectional imaging such as MRIs and CT scans as a guide when resecting a tumor and its surrounding tissue. But in many cases some cancerous tissue goes undetected and remains in the patient, sometimes making a second surgery and radiation therapy necessary.
“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 David Kirsch, MD, PhD, a professor of radiation oncology and pharmacology and cancer biology at Duke University School of Medicine, and senior author of the study. “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.”
Researchers all over the world are looking for techniques that can help surgeons better visualize cancer; a similar mechanism is LUM015 (pronounced as loom-fifteen), a blue liquid activated by enzymes. But the agent in this study is the first protease-activated imaging agent for cancer that has been tested for safety in humans, Kirsch said.
LUM015 was developed by Lumicell, a company started by researchers at MIT and involving Kirsch. In companion experiments in mice, LUM015 accumulated in tumors and created fluorescence in the tumor tissue that is on average 5 times brighter than regular muscle. The resulting signals are not visible to the naked eye; a handheld imaging device with a sensitive camera, which Lumicell is also developing, must be used to detect the fluoresced tissue, Kirsch explained.
After a tumor is removed, the surgeon places the handheld imaging device on the cut surface. The device then directs the surgeon to areas with fluorescent cancer cells.
Going into surgery, the goal is always to remove 100% of the tumor, plus a margin of normal tissue around the edges, explained Brian Brigman, MD, PhD, chief of orthopedic oncology at Duke and a senior author in the study. Pathologists then analyze the margins over several days to determine whether they are clear.
“This pathologic technique to determine whether tumor remains in the patient is the best system we have currently, and has been in use for decades, but it’s not as accurate as we would like,” said Brigman, who is also the director of the sarcoma program at the Duke Cancer Institute.
“If this technology is successful in subsequent trials, it would significantly change our treatment of sarcoma. If we can increase the cases where 100% of the tumor is removed, we could prevent subsequent operations and potentially cancer recurrence. Knowing where there is residual disease can also guide radiation therapy, or even reduce how much radiation a patient will receive.”