Statistics indicate that complete removal, or resection, of a tumor is the single most important predictor of patient survival for those with solid tumors. So, unsurprisingly, the first thing most patients want to know after surgery is whether the surgeon got everything. A new hand-held device called the SpectroPen could help surgeons provide a more definite and desirable answer by allowing them to see the edges of tumors in human patients in real time during surgery.
The SpectroPen combines a near-infrared laser and a detector to observe fluorescent dyes as well as scattered light from tiny gold particles that have been designed to stick to tumor cells. These particles consist of polymer-coated gold, coupled to a reporter dye and an antibody that sticks to the molecules on the outsides of the tumor cells. Through an effect called surface-enhanced Raman scattering, the gold in the particle greatly amplifies the signal from the reporter dye, allowing the researchers to detect tumors smaller than one millimeter grafted into rodents. The SpectroPen is connected by a fiber optic cable to a spectrometer that can record the fluorescence and Raman signals.
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The researchers used the SpectroPen to detect the dye indocyanine green, an FDA approved dye that had been infused intravenously into mice with implanted human breast cancer cells. Because of the leaky blood vessels and membranes surrounding tumors, the dye accumulates at a higher rate in tumor cells resulting in the SpectroPen’s signal from the tumor being ten times higher than from normal tissue.
As the cancer cells implanted in the mice had a gene from fireflies added, the tumors glowed after the mice were given a solution of “luciferin” – a light-emitting biological pigment that causes bioluminescence. This allowed the scientists to check that the outline of the tumor seen through the SpectroPen matched the glow.
“Our in vivo studies demonstrate that the tumor borders can be precisely detected preoperatively and intraoperatively, and that the contrast signals are strongly correlated with tumor bioluminescence,” said Shuming Nie, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
The interdisciplinary team responsible for the SpectroPen includes biomedical researchers from Emory University School of Medicine, the Georgia Institute of Technology, and the University of Pennsylvania, with different teams putting the technology to use in a number of ways. One team is developing an integrated spectroscopic and wide-field color imaging system for image-guided surgery and cancer detection during surgery using animal models. Another is currently using the device to operate on dogs with naturally occurring tumors, while one researcher is applying to conduct clinical trials involving patients with lung cancer.
The SpectroPen is described in an article published recently in the journal Analytical Chemistry.