This article first appeared in the St. Louis Beacon: Samuel Achilefu, professor of radiology at Washington University Optical Radiology Laboratory, is excited about how light, specifically near infrared light, can be used to identify cancers. To demonstrate how infrared light can help surgeons to see and remove tumors, he shows how a laser pointer penetrates deep into human tissue causing it to glow red. Ordinary white light tends to bounce back.
Using infrared light with a biomarker that binds to cancers and “lights up” the tumors and special goggles to help surgeons see the marked tumor, Achilefu and his research group hope to revolutionize the way in which surgeons visualize and remove cancers.
The goggles are "going to be like cool glasses that surgeons wear. You can walk around with them. You can look and see exactly what’s happening. But at the same time we are projecting that fluorescence right into his view. So he can do the surgery, see the cancer, yet not miss what’s going on (around him),“ Achilefu said.
Another surgeon originally provided the inspiration to invent goggles to help surgeons be more exact in removing cancers, Achilefu said.
“The surgeon came to me many years ago, and said, ‘You know, we have a problem. We get this beautiful CT image and X-ray scan. ... We see this cancer, but when we come into the operating room we don’t really know exactly where it is,’” Achilefu remembered.
He formed a team of researchers to develop the system.
Trial of goggles
Dr. Ryan Fields, assistant professor of surgery, and Dr. Julie Margenthaler, associate professor of surgery at Washington University School of Medicine, will use the goggles to perform biopsies on patients beginning later this month. They plan to complete a feasibility trial using the goggles during surgery on approximately 40 volunteer patients.
“It’s really just putting the goggles on and seeing how it works,” said Fields, whose specialty is removing melanoma. “We just want to see if it’s feasible.”
Fields said that the goggles have the potential to improve outcomes by helping surgeons to see clearly where cancers begin and end.
“A lot of times we’re relying on how something feels or looks,” he said.
CAT scans and MRI images sometimes fail to detect all cancer that is present, especially if it is microscopic, said Fields.
“If you could streamline the process so that during an operation you could identify microscopic cancers, you could treat it then and there, and you wouldn’t have to wait for a pathologist to evaluate everything,” he said.
Improving 'tumor margins'
When a tumor is removed, a pathologist examines the tissue, especially around the edges, for cancer cells.
If a pathologist finds “positive tumor margins,” cancer cells close to or on the edge of the removed tissue, it is likely that not all of the cancer was removed. That may trigger the need for another round of surgery or chemotherapy.
The problem is that tumors do not necessarily have clean edges, says Achilefu.
“When you do surgery, tumors are not always roundish as people may think,” says Achilefu. The tumor “has tentacles everywhere. After surgery, at least 25 percent of patients come back because they have positive margins (meaning that some cancer was not removed). That is terrible because of the cost, the anxiety, and everything that goes with it. Now we are trying to provide a tool that will stop that from happening,” Achilefu said.
Magic ingredient: Biomarker LS 301
The linchpin of the system is a biomarker that Achilefu says is the first contrast agent to mark cancer cells universally.
“We discovered an agent that can find cancer anywhere in the body, no matter where,” Achilefu said.
LS 301 selectively enters cancer cells. It fluoresces inside the cells when infrared light is shined upon it, revealing the tumor. Both infrared light and LS 301’s fluorescence are invisible to the naked eye. The surgeon can see the tumor while wearing the goggles.
Accidental discovery
Achilefu said that he stumbled on the LS 301 biomarker when he was trying to create a control that would not go into cancer cells.
“I designed the whole thing (LS 301) in such a way that it shouldn’t go to cancer cells,” he said. “So, it was a disappointment for two years.”
But, as LS 301 stubbornly insisted in going into and staying in many different types of cancer cells, Achilefu and his group began to look at the biomarker differently.
They tested it and found that it selectively bound to breast, prostate, liver, brain, colon, leukemia and lymphoid cancers, and that it stayed in the cancer cells for about a week. It even bound to cancer stem cells, Achilefu said.
Suman Mondal, a graduate student in Achilefu’s group, said that the group is not exactly sure why LS 301 goes into and stays selectively in cancer cells, but that the biomarker binds to integrins, proteins found on the cell membranes of cancers.
“It gets accumulated around tumors because of integrins,” Mondal said. The group also believes that a disulfide bond in LS 301 is broken once it enters the cell, causing LS 301 to bind to sites inside the cancer cell.
Because LS 301 has not yet been approved for human use, Margenthaler and Fields will use indocyanine green, an FDA-approved infrared fluorescing agent, in this clinical trial. The goggle system has already been used on human liver cancer patients using indocyanine green with encouraging results. The study found that, in addition to tumors already visualized by MRI and CT scans, surgeons wearing the goggles were able to see additional liver cancer tumors not detected by other imaging techniques. The results were published this year in the journal Translational Research.
Achilefu is optimistic about the agent’s capability to serve not only as a marker for malignant tumors but as a drug delivery system as well.
Achilefu also hopes that LS 301 be used to see how tumors react to chemotherapy.
Removing tumors in dogs
To ready LS 301 for approval for human use, the research team is preparing to begin animal studies on LS 301. The group will work in conjunction with the University of Missouri School of Veterinary Medicine to identify and remove cancerous tumors in dogs. Achilefu said that the study will work with dogs whose owners have agreed to allow the dogs to participate.
“This improves the chances of recovery after the surgery. We’re trying to make sure all the tumor tissue is taken out, and nothing is left behind,” he said. “So, we are going to save the dog, we are going to improve the treatment outcome.”
Once the toxicology studies are completed in canine patients, the research group will work with the Siteman Cancer Center staff to submit an application to the FDA.
Funding
Currently, the fluorescing goggles project is supported by grants from the National Cancer Institute and the National Institute of Biomedical Imaging and Bioengineering.
But Achilefu says that he has already had offers from firms outside of St. Louis that would like to develop LS 301.
“Actually I could have been a rich man today if I had (taken an offer from a company) that wanted to take it away from St. Louis, move it to the Bay Area,” he said.
He is not interested, because he wants to keep the system, his students and all the potential development in St. Louis.