H. Shao, J. Chung, L. Balaj, A. Charest, D. D. Bigner, B. S. Carter, F. H. Hochberg, X. O. Breakefield, R. Weissleder, and H. Lee. Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat Med, 18(12):1835–1840, Dec 2012. [PubMed Central:\href https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518564PMC3518564] [DOI:\href https://dx.doi.org/10.1038/nm.299410.1038/nm.2994] [PubMed:\href https://www.ncbi.nlm.nih.gov/pubmed/2152756321527563].


Glioblastomas shed large quantities of small, membrane-bound microvesicles into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Here, we describe a highly sensitive and rapid analytical technique for profiling circulating microvesicles directly from blood samples of patients with glioblastoma. Microvesicles, introduced onto a dedicated microfluidic chip, are labeled with target-specific magnetic nanoparticles and detected by a miniaturized nuclear magnetic resonance system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate glioblastoma multiforme (GBM) microvesicles from nontumor host cell-derived microvesicles. We also show that circulating GBM microvesicles can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials.