Surgeons who operate on patients with ovarian cancer face a tough challenge. They need to remove as much of a tumor as possible, but small cancerous nodules that spread from the ovaries into other organs can hide in folds of tissue, evading a surgeon’s trained eye. Finding them is critical, since the best outcomes for patients depend on leaving no cancer behind.

One way to make the nodules easier to see is by labeling them with a fluorescent probe that binds only to tumor tissue, causing it to glow. Australian researchers recently achieved promising results with this method, which could help to ensure that cancer is eliminated from a woman’s body during a surgical procedure.

“Surgeons want to get to the point where they say, ’We can’t find any more tumors,’” says John Hooper, a cancer pathologist at the University of Queensland who helped lead the research. “We want them to be able to say that with more certainty.”

Surgeons already use a marker called indocyanine green, which glows brightly when exposed to near infrared light to improve the visibility of liver, lung, colon, and other cancers. Yet, indocyanine green does not bind to ovarian cancers with enough specificity for clinical applications.

Hooper and his team hope to change that. They specialize in developing compounds that bind to specific proteins and molecules on cancer cells. The aim, Hooper says, is to employ the compounds for ferrying payloads of markers or therapeutic agents to the cells.

During this project, the researchers took a  mouse monoclonal antibody called 10D7 that binds strongly to CDCP-1, a protein that’s abundant on the surface of ovarian cancer cells, and they attached indocyanine green to the antibody.

When the labeled antibody was released near ovarian cancer cells, its Y-shaped arms bound to the cells. The researchers then fused the labeled arms to the stem of a human antibody, generating a hybrid called a humanized mouse antibody. By attaching indocyanine green to this hybrid antibody, they generated a probe suitable for clinical use, Hooper says, because it can sneak past a patient's immune system.  

The researchers then injected the probes into two groups of tumor-bearing mice—one that had been freshly inoculated with commercially available ovarian cancer cell lines, and a second that had been inoculated with fresh human tumor material.  

After letting the tumors grow, the researchers exposed their internal anatomy. When illuminated under infrared light, “every cell that expressed the CDCP-1 protein was lit up like a Christmas tree,” Hooper says.  By contrast, indocyanine green delivered to control animals without the antibody did not accumulate in tumors at all. Hooper and his colleagues reported the results in Molecular Pharmaceutics, published by ACS Publications, a division of the American Chemical Society.

Hooper speculates that doctors could administer the fluorescent probe intravenously an hour or so before surgery. The probe would travel via the bloodstream, then home in and attach itself to rogue cancer cells. At that point, surgeons operating under a shining infrared light could find and remove the glowing nodules. This would increase the likelihood of a successful procedure and improve chances for long-term survival.

According to Hooper, biotechnology companies and venture capitalists have already come knocking. “There’s a lot of excitement around this research,” he says. “We’re hoping we can go into clinical trials soon.”

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