Particulate matter: NMR checks on brain cancer

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  • Published: Dec 1, 2012
  • Channels: NMR Knowledge Base
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Microvesicles

Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy

NMR relaxometry can be used to detect the minuscule cell particles (microvesicles) that are shed by cancer cells and enter the blood stream. The approach offers the potential for a simple, inexpensive and relatively non-invasive way to diagnose and monitor brain cancer researchers say.

The most common and aggressive form of brain cancer, glioblastoma multiforme (GBM), has a poor prognosis unless diagnosed and treated very early. Unfortunately diagnosis is difficult and patients typically do not live much more than a year following diagnosis. However, if it is diagnosed there is the added problem of ensuring that the treatment is having a positive effect and so monitoring during the various types of therapy available is critical if the chances of life extension are to be improved.

From 'cell dust' to biomarkers

At the moment, repeated surgical biopsies and medical imaging are the only effective approach to tracking the effects of treatment. If there were a simple blood test, then oncologists would have a much less invasive way to follow disease progression and remission in their patients. One possible focus is the microvesicles shed into the blood by cells and in higher numbers by cancer cells in particular. These particles can cross the blood-brain barrier, unlike circulating tumour cells, which are too large.

"About 30 or 40 years ago, people noticed something in the bloodstream that they initially thought was some kind of debris or 'cell dust'," explains Hakho Lee of the Massachusetts General Hospital (MGH) Center for Systems Biology (CSB). "But it has recently become apparent that these vesicles shed by cells actually harbour the same biomarkers as their parent cells." Writing alongside CSB director Ralph Weissleder and colleagues in the journal Nature Medicine, the team has demonstrated how NMR relaxometry can be used to detect the biomarkers of GBM in such microvesicles from a single drop of blood, paving the way for a reliable and essentially non-invasive diagnostic. 

NMR tumour detection

"The issue with microvesicles, however, is that they are very small, so there are not many technologies out there that can detect and molecularly profile them," explains Lee. "That is where our new technology comes in." The team uses magnetic nanoparticles to label microvesicles present in a blood sample. They have also adapted and improved equipment they developed in 2011 for cancer cell detection to implement a miniature, portable NMR machine for analysing tumour microvesicles present in blood. Initial tests on blood samples from mice bearing human GBM tumours were successful and they have now tested samples from human GBM patients.

"These microvesicles were found to be remarkably reliable biomarkers," Weissleder says. "They are very stable and abundant and appear to be extremely sensitive to treatment effects. In both animals and human patients, we were able to monitor how the number of cancer-related microvesicles in the bloodstream changed with treatment," explains Weissleder. "Even before an appreciable change in tumour size could be seen with imaging, we saw fewer microvesicles. It's like they are a harbinger of treatment response."

Compared with other common techniques, this new approach is much more accurate but has the added advantage of not being time-consuming nor requiring large sample volumes. Moreover, it can be carried out without the expertise required in taking biopsies or medical imaging. NMR detection is quick and simple and could give almost instantaneous results in the oncologist's office.

The researchers are now extending the system to other types of cancer and to other diseases such as bacterial infection, which are also associated with specific biomarkers present in the blood. Clinical trials are underway.

Related Links

Nature Med, 2012: "Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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