In a paper epubbed in Nature Medicine this week, researchers at Stanford showed a new technique for tagging glios using nanoparticles. Glios (glioblastoma multiforme) are the Darth Vader of brain tumors. Originating in glial cells which form the crucial supporting white matter of the brain, glios spread extremely aggressively and carry the worst prognosis of all primary CNS neoplasms in adults. They are, sadly, the most common of all primary CNS neoplasms in adults. Treatment does little to extend life, and may not even be able to palliate symptoms in some cases. Glios are also among the most invasive of all brain tumors – since they originate from the supporting and supply network of the brain, they often infiltrate in unpredictable ways through important areas.
So what good is tagging a glio, anyways? To answer that question, it’s important to understand the challenges in treatment.
According to Greenberg, the literature is conflicting. On the one hand, some studies show that “the extent of tumor removal [has] a significant effect on time to tumor progression and median survival” but even when there is no residual tumor tissue on post-op MRI, this improvement is only on the order of 5 months (11.8 vs 16.7 months, Greenberg p.600). Some argue that surgery helps improve the outcomes from chemotherapy (Greenberg p. 601). However, there are a few important limitations to surgery:
1. Tumor may be located in eloquent areas where resection would cause an unacceptable decrease in neurologic function.
2. Operator may be unable to differentiate between normal tissue and tumor.
3. Patient may be unable to tolerate craniotomy.
At the end of the day, it would be reasonable to think that if we could somehow have a better way to tell the difference between normal tissue and tumor beyond our standard Mark 1 Eyeball, we might be able to better address these tumors.
Enter the Stanford study. They used specially designed nanoparticles that bind preferentially to tumor tissue. These nanoparticles are smaller than red blood cells and could slip out through the leaky blood vessels that commonly supply tumors to lodge in the nearby tissue. The particles are coated with gadolinium for MRI contrast effects, contain gold cores that they can be detected on ultrasound when light hits them (this technique is called photoacoustic imaging), and give off a characteristic light pattern that can be visualized with a special operating microscope (Raman imaging). This triple technique allows surgeons to visualize the particles pre-, intra- and post-operatively via MRI, and in realtime using the specially equipped microscopes.
(Kircher et al.Nat Med 2012)
The results in an initial mouse model using a human glioblastoma line were consistent with what was expected. The Raman intraoperative imaging helped find a small additional area of tumor during the surgical resection, which was then excised to accomplish an apparently total resection.
BOTTOM LINE: A fascinating experimental technique using nanoparticles which can be visualized pre-, intra- and post-operatively. This technique should be evaluated for tolerability and effectiveness in humans. If tolerable, clinical relevance could then be investigated.