Fluorescence-guided multispectral imaging method promising for ovarian cancer surgery

Using a cancer cell fluorescence imaging agent coupled with a multispectral fluorescence camera, Purdue University (West Lafayette, IN) researchers performed fluorescence-guided ovarian cancer surgery on a patient, which illuminates cancer cells to help surgeons identify and remove smaller tumors that could otherwise be missed. The surgery was one of 10 performed as part of the first phase of a clinical trial to evaluate new technologies to aid surgeons in the removal of malignant tissue from ovarian cancer patients.

Surgeons using the Purdue research team's fluorescence method were able to see clusters of cancer cells as small as one-tenth of a millimeter, as opposed to the earlier average minimal cluster size of 3 mm in diameter based on current methods of visual and tactile detection, says Philip Low, the Ralph C. Corely Distinguished Professor of Chemistry who invented the technology.

Published in the September 18 issue of Nature Medicine, the method attaches a fluorescent imaging agent to a modified form of the vitamin folic acid, which acts as a "homing device" to seek out and attach to ovarian cancer cells. Patients are injected with the combination two hours prior to surgery and a multispectral fluorescence camera then illuminates the cancer cells and displays their location on a flat-screen monitor next to the patient during surgery.

The surgeons involved in this study reported finding an average of 34 tumor deposits using this method, compared with an average of seven tumor deposits using visual and tactile observations alone.

A surgeon's view of ovarian cancer cells with and without the tumor-targeted fluorescent imaging agent. (Image courtesy of Gooitzen van Dam)

Gooitzen van Dam, a professor and surgeon at the University of Groningen in The Netherlands where the surgeries took place, said the imaging system fits in well with open and laparoscopic surgery, which is the direction most surgeries are headed in the future.

The technology is based on Low's discovery that folic acid, or folate, can be used as a way to sneak an imaging agent or drug into a cancer cell, as ovarian cancer has an 85% folate receptor expression rate—one of the highest rates. Most ovarian cancer cells require large amounts of the vitamin to grow and divide, and special receptors on the cell's surface grab the vitamin—and whatever is linked to it—and pull it inside. Not all cancer cells express the folate receptor, and a simple test is necessary to determine if a specific patient's cancer expresses the receptor in large enough quantities for the method to work, says Low.

Low also is investigating targeting molecules that could be used to carry attached imaging agents or drugs to forms of cancer that do not have folate receptors. He next plans to develop a red fluorescent imaging agent that can be seen through the skin and deep into the body. The current agent uses a green dye that had already been through the approval process to be used in patients, but cannot easily be seen when present deep in tissue. Green light uses a relatively short wavelength that limits its ability to pass through the body, whereas the longer wavelengths of a red fluorescent dye can easily be seen through tissue.

The clinical trial was funded by Endocyte Inc. and the University Medical Center of Groningen.

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