|
The first fluorescence-guided surgery on an ovarian cancer
patient was performed using a cancer cell “homing device” and imaging
agent created by a Purdue
University researcher.
The surgery was one of 10 performed as part of the first
phase of a clinical trial to evaluate a new technology to aid surgeons in the
removal of malignant tissue from ovarian cancer patients. The method
illuminates cancer cells to help surgeons identify and remove smaller tumors
that could otherwise be missed.
Philip Low, the Ralph C. Corely Distinguished Professor of
Chemistry who invented the technology, says surgeons 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.
“Ovarian cancer is notoriously difficult to see, and
this technique allowed surgeons to spot a tumor 30 times smaller than the smallest
they could detect using standard techniques,” says Low, who also is a
member of the Purdue
University Center
for Cancer Research. “By dramatically improving the detection of the
cancer—by literally lighting it up—cancer removal is dramatically improved.”
The technique 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 special camera
system, called 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 technique, compared with an average of
seven tumor deposits using visual and tactile observations alone. A paper
detailing the study was published online in Nature
Medicine.
Gooitzen van Dam, a professor and surgeon at the University of Groningen in The Netherlands where the
surgeries took place, says the imaging system fits in well with current
surgical practice.
“This system is very easy to use and fits seamlessly
in the way surgeons do open and laparoscopic surgery, which is the direction
most surgeries are headed in the future,” says van Dam, who is a surgeon
in the division of surgical oncology and Bio-Optical Imaging Center at the
University of Groningen. “I think this technology will revolutionize
surgical vision. I foresee it becoming a new standard in cancer surgery in a
very short time.”
Research has shown that the less cancerous tissue that
remains, the easier it is for chemotherapy or immunotherapy to work, Low says.
“With ovarian cancer it is clear that the more cancer
you can remove, the better the prognosis for the patient,” he says.
“This is why we chose to begin with ovarian cancer. It seemed like the
best place to start to make a difference in people’s lives.”
By focusing on removal of malignant tissue as opposed to
evaluating patient outcome, Low dramatically reduced the amount of time the
clinical trial would take to complete.
“What we are really after is a better outcome for patients,
but if we had instead designed the clinical trial to evaluate the impact of
fluorescence-guided surgery on life expectancy, we would have had to follow
patients for years and years,” he says. “By instead evaluating if we
can identify and remove more malignant tissue with the aid of fluorescence
imaging, we are able to quantify the impact of this novel approach within two
hours after surgery. We hope this will allow the technology to be approved for
general use in a much shorter time.”
Low and his team are now making arrangements to work with
the Mayo Clinic for the next phase of clinical trials.
The technology is based on Low’s discovery that folic
acid, or folate, can be used like a Trojan horse to sneak an imaging agent or
drug into a cancer cell. 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 technique to work, he says.
Ovarian cancer has one of the highest rates of folate
receptor expression at about 85%. Approximately 80% of endometrial, lung, and
kidney cancers, and 50% of breast and colon cancers also express the receptor,
he says.
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.
“We want to be able to see deeper into the tissue,
beyond the surface,” Low says. “Different cancers have tumors with
different characteristics, and some branch and wind their way deeper into
tissue. We will continue to evolve this technology and make improvements that
help cancer patients.”
