Researchers at Carnegie Mellon University (CMU), in Pittsburgh, are using fluorescent nanoparticles to image tumor tissue during biopsies and surgeries. The imaging technique, which is being tested in rodents, could be particularly useful for precisely spotting tumors during surgeries to remove glioblastomas, one of the most common and aggressive forms of brain cancer. On average, patients survive less than a year after their diagnosis with this deadly form of brain cancer, in part because of the difficulty of surgically removing the entire tumor.
Led by CMU chemist Marcel Bruchez and Steven Toms, director of neurosurgery at the Geisinger Clinic, in Danville, PA, the researchers took crisp fluorescent images of brain tumors, called gliomas, in rats. The rats had been injected with nanoparticles that emit infrared light when they are excited by visible light. The infrared rays made by the nanoparticles can be picked up by a small camera and viewed by surgeons. These quantum dots have a core made of cadmium and telluride, surrounded by a zinc-sulfide shell, which is in turn surrounded by a protective polymer coating.
“This particular type of tumor is poorly distinguishable,” says Bruchez. And when removing brain tumors, surgeons can’t cut wide margins, or patients might lose brain function.
Surgeons removing a brain tumor now rely on a recently taken picture from magnetic resonance imaging (MRI) to orient themselves. But, says Bruchez, “the consistency of the brain is like a bowl of Jell-O. Once you start cutting and removing tissue, things move around, and you can’t rely on presurgery imaging.” He says that surgeons leave behind glioma tissue more than half the time.
One solution to the problem is to run several MRI scans on the patient during the surgery. With this extra guidance, one study showed, surgeons can remove about 15 percent more glioma tissue. But operating rooms that incorporate MRI are expensive, and surgeons must use special tools that won’t be affected by the MRI magnet.
Bruchez and Toms found that glowing quantum dots injected into a rat’s bloodstream are brought to glioma tissue–but not to other areas of the brain–by immune cells called macrophages. These cells engulf debris like nanoparticles and swarm to infected and cancerous tissues as part of the body’s inflammatory response. The macrophages do not go to healthy brain tissue.
Bruchez wants to build an imaging system that’s compatible with standard operating procedures. Outfitting an operating room for infrared imaging of tumors would involve adding an infrared digital camera and installing filters on the lights to eliminate ambient infrared light, ensuring that the only infrared light in the room comes from quantum dots. The quantum dots can be tuned to emit visible light, which would eliminate the need for the imaging system, but doctors would have to turn off the lights to see the glow from tumors, then turn them back on and readjust their eyes to continue with surgery.
Bruchez says that he and his collaborators have had good results using a system based on the technology to perform surgical removal of tumors in rodents, although these results are as yet unpublished. He expects the work to apply generally to various types of cancers; other unpublished research by his group, he says, demonstrates that the tendency of macrophages to gobble up quantum dots and travel with them to tumor tissue holds for many other cancers.
Bruchez and Toms are also developing biopsy needles with optical imaging systems. Brain-tumor biopsies are normally time consuming and hit or miss. “You go where you believe the tumor to be, take out a sample, send it to the pathology lab, and wait in the operating room for the results,” says Bruchez. If the surgeons missed the tumor, they have to take another sample and wait for the results again. If a patient were first injected with tumor-seeking quantum dots that could be detected by the biopsy needle, the process might be that much easier.
The safety of quantum dots for brain imaging still needs to be investigated. The cores of the quantum dots used by Bruchez are made of cadmium, and although there is no evidence so far that cadmium-containing quantum dots are toxic, some researchers are wary. “Cadmium is very toxic,” points out Wenbin Lin, a chemist at the University of North Carolina who is developing nanoparticles for high-contrast MRI. “We need to worry about that.”
Indeed, says Bruchez, “there are concerns with cadmium, but the formulation that is used for fluorescence imaging should render the cadmium nonbioavailable.” The organic polymers surrounding the cadmium can’t be broken down by typical biological processes, he says. However, to address toxicity concerns, Bruchez says he is developing imaging techniques that require lower doses of the particles and encapsulation methods that render the metal even less bioavailable.
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