A major challenge of brain tumor surgery is removing all of the cancer while preserving as much healthy brain tissue as possible. Because surgeons cannot cut wide margins around the tumor, cancer cells may be left behind.
Now a multi-institutional team of researchers from Memorial Sloan Kettering, Stanford University, and Weill Cornell Medical College has demonstrated a new technique that enables specific and accurate labeling of brain tumor tissue in mice. If the method is proven effective in patients, it could make complete surgical removal of brain tumors more feasible.
“One of the difficulties of neurosurgery is that the unaided eye can’t see the precise borders of the tumor,” says Memorial Sloan Kettering radiologist and molecular imaging scientist Moritz Kircher, the first author of the study published online April 15 in Nature Medicine. For example, an aggressive brain tumor called glioblastoma is characterized by irregular edges and small, fingerlike projections into healthy tissue, making these tumors especially difficult to remove completely.
“We hope our technique will be helpful in showing surgeons exactly where the borders of the tumor are located,” Dr. Kircher adds. “It may also be useful in finding cancer cells that have spread away from the primary tumor site.”
The technique makes use of tiny molecules called triple-modality nanoparticles, which are many times smaller than cells. After being injected into the blood, the nanoparticles are able to home in on brain tumor cells and tag them with a label so the cells can be more easily detected. The particles remain in the cells for several days, so that one single dose can be used for both planning the surgery and as a guide during the surgical procedure.
These particles – the first of their kind – have unique properties that allow them to be seen using three complementary imaging technologies: MRI, which images the entire brain and the tumor; photoacoustic imaging, which can visualize the tumor in three dimensions in the operating room; and surface-enhanced Raman spectroscopy (SERS) imaging, a type of imaging that has ultra-high sensitivity and resolution and can visualize microscopic residual tumor.
Both photoacoustic and Raman imaging are newer, experimental techniques that are based on the molecular interactions of a laser with the nanoparticle. In fact, this study is the first to demonstrate SERS imaging of a disease inside a living animal.
Advanced Mouse Models
The study was performed in two mouse models of glioblastoma. One of the models was developed in the laboratories of study co-authors Ingo Mellinghoff and Eric Holland of Memorial Sloan Kettering. This model resembles human glioblastoma tumors quite closely, mimicking the way these tumors grow and spread in a patient’s brain.
The study found that when the nanoparticles were injected into the mice, they accumulated in all of the tumor tissue, but were not found at all in the surrounding healthy tissue. More research is needed to determine if the nanoparticles are safe before investigators can begin studying them in clinical trials for patients.
“In the future, we envision the way this technique would be used is that after being given the nanoparticles, the patient would get an MRI for staging and presurgical planning,” Dr. Kircher explains. “Then the neurosurgeon could use handheld photoacoustic imaging and Raman imaging devices to see the particles during surgery so that he or she would be able to completely remove the tumor without harming any healthy brain structures.”