|Nanoparticles that can be imaged three different ways at once have enabled Stanford University School of Medicine scientists to remove brain tumors from mice with unprecedented accuracy.|
The study published online April 15 in Nature Medicine, a team led by Sam Gambhir, MD, PhD, professor and chair of radiology, showed that the minuscule nanoparticles engineered in his lab homed in on and highlighted brain tumors, precisely delineating their boundaries and greatly easing their complete removal. The new technique could someday help improve the prognosis of patients with deadly brain cancers.
About 14,000 people are diagnosed annually with brain cancer in the United States. Of those cases, about 3,000 are glioblastomas, the most aggressive form of brain tumor. The prognosis for glioblastoma is bleak: the median survival time without treatment is three months. Surgical removal of such tumors — a virtual imperative whenever possible — prolongs the typical patient’s survival by less than a year. One big reason for this is that it is almost impossible for even the most skilled neurosurgeon to remove the entire tumor while sparing normal brain.
The nanoparticles used in the study are essentially tiny gold balls coated with imaging reagents. Each nanoparticle measures less than five one-millionths of an inch in diameter — about one-sixtieth that of a human red blood cell.
“We hypothesized that these particles, injected intravenously, would preferentially home in on tumors but not healthy brain tissue,” said Gambhir, who is also a member of the Stanford Cancer Institute. “The tiny blood vessels that feed a brain tumor are leaky, so we hoped that the spheres would bleed out of these vessels and lodge in nearby tumor material.” The particles’ gold cores, enhanced as they are by specialized coatings, would then render the particles simultaneously visible to three distinct methods of imaging, each contributing uniquely to an improved surgical outcome.
One of those methods, magnetic resonance imaging, is already frequently used to give surgeons an idea of where in the brain the tumor resides before they operate. MRI is well-equipped to determine a tumor’s boundaries, but when used preoperatively it can’t perfectly describe an aggressively growing tumor’s position within a subtly dynamic brain at the time the operation itself takes place.
The Gambhir team’s nanoparticles are coated with gadolinium, an MRI contrast agent, in a way that keeps them stably attached to the relatively inert spheres in a blood-like environment. (In a 2011 study published in Science Translational Medicine, Gambhir and his colleagues showed in small animal models that nanoparticles similar to those used in this new study, but not containing gadolinium, were nontoxic.)
“With brain tumors, surgeons don’t have the luxury of removing large amounts of surrounding normal brain tissue to be sure no cancer cells are left,” said Gambhir, who is the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research and director of the Molecular Imaging Program at Stanford. “You clearly have to leave as much of the healthy brain intact as you possibly can.”
A second, newer method is photoacoustic imaging, in which pulses of light are absorbed by materials such as the nanoparticles’ gold cores. The particles heat up slightly, producing detectable ultrasound signals from which a three-dimensional image of the tumor can be computed. Because this mode of imaging has high depth penetration and is highly sensitive to the presence of the gold particles, it can be useful in guiding removal of the bulk of a tumor during surgery.
The third method, called Raman spectroscopy, leverages the capacity of certain materials (included in a layer coating the gold spheres) to give off almost undetectable amounts of light in a signature pattern consisting of several distinct wavelengths. The gold cores’ surfaces amplify the feeble Raman signals so they can be captured by a special microscope.
To demonstrate the utility of their approach, the investigators first showed via various methods that the lab’s nanoparticles specifically targeted tumor tissue, and only tumor tissue.
SOURCE Stanford School of Medicine
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