

To Find More Tumors, Scientists Make Cancer Glow

In a new study, an international research team tagged ovarian tumor molecules with fluorescent dye to make them glow bright green. The researchers hope that adopting this method will allow doctors to remove more cancer during surgery by catching tumors they missed with the naked eye.
Philip Low

The success of cancer surgery hinges on how much of the diseased tissue a surgeon can extract. But the doctors can remove only the tumor they can find through sight and touch, meaning some cancer gets left in the patient. To get more of it, there has to be a better method than using the human eye.

One approach, just tested by a team of scientists from universities in the Netherlands, Germany and the United States, is to make cancer glow. For a study published in this week's Nature Medicine, the team targeted ovarian cancer tumors with fluorescent dye. And in an early-stage trial with 10 ovarian cancer patients, fluorescent imaging helped scientists find an average of 34 tumors, compared with the average of seven they found using the traditional visual and tactile methods.

The key to the project is ovarian cancer cells' enormous appetite for the vitamin folic acid, or folate. They need it to divide properly, and cancer cells divide voraciously, says Philip Low, a biochemist at Purdue University and inventor of the technology. "We take advantage of this greed by using the vitamin as a Trojan horse to carry the imaging agent selectively into the cancer cell," he says.

Low attaches the fluorescent imaging agent to folate, then injects that folate into patients a couple of hours before surgery. Regular body cells have few or no receptors for folate, but in most ovarian cancer patients—about 85 percent of them—the cancer cells have a plethora of folate receptors. So cancer cells and not normal ones gobble up that dyed folate, and under fluorescent light, only cancerous cells glow.


In this trial, surgeons injected the patients with dyed folate and then first performed tumor excisions the way they normally do, using their eyes and hands. But once doctors removed all the cancer they could see, they flipped on a camera system that filters out the light from the operating room and shows only the fluorescent wavelength. "The cancer tissue lights up like a light bulb," Low says.

"The surgeons are ready for this technique," says Robert Gillies, the director of molecular and functional imaging at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., who was not involved in the study. "It will revolutionize surgeries, because it combines molecular biology knowledge with this targeted imaging technique."

But the technology is still in its infancy, Gillies says. "The FDA is being appropriately cautious about this." One reason is that the new study didn't test for clinical outcomes. Low and colleagues showed that the technique can make cancer easier to see, but the FDA needs the hard data that shows the strategy helps more patients survive in the long run. For any drug or procedure, that takes time.

Another caveat is that this approach doesn't work for everyone. Low says that 85 percent of ovarian tumors have enough folate receptors that they glow well to be seen during surgery, and while that's quite good, it also means 15 percent don't. And the numbers are different for different cancers. Some, like endometrial, lung and kidney cancers, express the folate receptor about 80 percent of the time. For breast cancer, it's about 50 percent of the time. Other cancers don't express folate receptors at all.

This means that doctors can't target folate receptors exclusively for any kind of cancer. But it's not a dead end: Instead, they'll have to find different molecules to target for each kind of cancer. "By changing the active molecule, you can fine-tune [the fluorescence technique] for different cancers," says study co-author Vasilis Ntziachristos.

Targeting different types of cancer differently is good, Gillies says. But targeting each unique tumor in its own way, identifying a target molecule for each individual patient, would be even better. "It's going to have to have some aspect of personalized medicine," Gillies says.

Low says: "The way I envision it, we will take a sample of the patient's blood [to find what kind of receptor is the best candidate]. Then we will use the targeting molecule for that receptor and use it for therapy, for imaging, for everything. That's pie in the sky, wild anticipation of 20 years down the road, but it can be done. It's a matter of doing the work now."

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