Surgeons turn to fluorescence to zero in on cancer cells hidden among a tangle of nerves and blood vessels

Rebecca C. Jernigan

The goal of cancer surgery is to remove all of the malignant cells, while leaving as much undamaged tissue as possible. Care and precision are demanded to walk this fine line, and surgeons do all that they can to maximize their patients’ chances. However, it can be difficult to differentiate between cancerous and noncancerous tissue visually, and nerves and blood vessels can remain hidden until it is too late to avoid them.

A team of researchers at Beth Israel Deaconess Medical Center in Boston, led by Dr. John Frangioni, has developed a system to help identify both cancerous tissue and critical structures. Called FLARE (Fluorescence-Assisted Resection and Exploration), the method is detailed in a paper that was presented in August at the 236th National Meeting of the American Chemical Society. It consists of a near-IR imaging system, a video monitor and computer, and a high-power LED-based light source with integrated linear drivers and temperature monitoring. It has no moving parts and does not touch the patient, which keeps it sterile.

The FLARE system has been used for near-IR fluorescent sentinel lymph node mapping of a swine foot using indocyanine green adsorbed to human serum albumin. The imaging system permits simultaneous acquisition of color video (left) and of otherwise invisible near-IR fluorescence (center), while the computer can superimpose the images on screen (right). Courtesy of John Frangioni.

The system uses fluorophores that target cancer. When exposed to near-IR light, the dyes fluoresce, and the malignant cells are displayed on the monitor, superimposed over images of the normal surgical field. This imaging system makes it simpler for surgeons to identify cancerous regions. The investigators have engineered an independent second fluorescence channel for the avoidance of critical structures. It uses a near-IR fluorescent blood pool agent for angiography – that is, avoiding blood vessels. Other groups are investigating nerve-specific agents, which may also be combined with the FLARE system. The computerized technique enables users to control multiple viewing angles and magnification levels through the use of a foot switch.

The group is in the process of performing its first human studies with the system, using an institutional review board-approved six-patient pilot study in sentinel lymph node mapping of breast cancer to validate the ergonomics, to refine the software and to choose the optimal imaging parameters. A larger study, comparing near-IR fluorescence to the standard of care, will begin once the current study is complete.

GE Healthcare of Chalfont St. Giles, UK, has licensed the FLARE technology and is conducting its own human trials. However, Frangioni said that his laboratory will be publishing complete design control documentation on its Web site to enable other academic groups to create their own versions of the system.