The combination of a fluorescence imaging agent and a multispectral fluorescence camera has enabled image-guided excision of extremely small tumors as part of a clinical trial designed to evaluate new technologies for ovarian cancer surgery. In the trial, surgeons using the method were able to see clusters of cancer cells as small as 0.10 mm. The surgeons reported finding an average of 34 tumor deposits using the new method, compared with an average of seven tumor deposits using visual and tactile detection—the current standard method, which is able to detect an average minimal cluster size of 3 mm in diameter, according to Philip Low, Ralph C. Corely Distinguished Professor of Chemistry at Purdue University (West Lafayette, IN) who developed the technology.1
The newly developed imaging agent attaches to a modified form of the vitamin folic acid, which in turn seeks out and attaches 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. According to Prof. Gooitzen van Dam of the University of Groningen (The Netherlands), where the surgeries took place, the approach 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 (folate) can be used to introduce an agent or drug into a cancer cell, as ovarian cancer has an extraordinarily high folate receptor expression rate, 85%. In fact, most ovarian cancer cells require large amounts of folate to grow and divide; receptors on the cell’s surface attract and facilitate absorption of the vitamin and whatever is linked to it. Not all cancer cells express the folate receptor, however; a simple test can determine whether the method will work for a specific patient.
The current agent uses a green dye that is approved for use in patients, but cannot easily be seen when present deep in tissue. Low plans to develop a red fluorescent probe whose wavelength will enable visualization through the skin and deep into the body. He is also investigating molecules that could be used to carry attached probes or drugs to forms of cancer that do not have folate receptors. The current research was funded by Endocyte Inc. and the University Medical Center of Groningen.
1. G.M. van Dam, Nat. Med. 17, 1315–1319 (2011).
