Surgery is a mainstay to treat malignant brain tumors. However, due to the infiltrative nature of these tumors, it is a great challenge for surgeons to accurately identify and excise all the tumor foci. EGFRvIII, a variant of epidermal growth factor receptor (EGFR), is found in 20% of glioblastoma cases, which is the brain tumor with the highest malignancy. In this study, we developed an EGFRvIII-targeted nanoprobe to guide glioblastoma surgery by pre-operatively defining the tumor boundary via magnetic resonance imaging (MRI) and intra-operatively guiding resection by surface-enhanced resonance Raman scattering (SERRS) imaging. In vivo MRI studies show that this nanoprobe delineates an orthotopic EGFRvIII+ U87MG glioblastoma xenograft with a higher target to background ratio than the control nanoprobe without targeting specificity. With the assistance of a handheld Raman scanner, this nanoprobe successfully guided EGFRvIII+ glioblastoma resection by tracking its characteristic SERRS signal peaks. Ex vivo Raman microscopy and histological images verified that this nanoprobe precisely demarcated the glioblastoma boundary and no residual neoplastic foci were observed in the tumor bed. This dual-modal nanoprobe not only precisely guided glioblastoma resection, but also overcame the brain shift induced false-positive signal by real-timely co-registering pre-operative and intra-operative images. This nanoprobe is promising for the improvement in diagnostic accuracy and surgical outcome of EGFRvIII+ glioblastoma.
Blood-brain barrier (BBB) disruption is frequently observed in the glioma region. However, the tumor uptake of drugs is still too low to meet the threshold of therapeutic purpose.Method: A tumor vasculature-targeted nanoagonist was developed. Glioma targeting specificity of the nanoagonist was evaluated by in vivo optical imaging. BBB permeability at the glioma margin was quantitatively measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Single-photon emission computed tomography imaging/computed tomography (SPECT/CT) quantitatively determined the glioma uptake of the radiolabeled model drug. T2-weighted MRI monitored the tumor volume.Results: Immunostaining studies demonstrated that the BBB remained partially intact in the invasive margin of patients' gliomas regardless of their malignancies. DCE-MRI showed that vascular permeability in the glioma margin reached its maximum at 45 min post nanoagonist administration. In vivo optical imaging indicated the high glioma targeting specificity of the nanoagonist. SPECT/CT showed the significantly enhanced glioma uptake of the model drug after pre-treatment with the nanoagonist. Image-guided paclitaxel injection after nanoagonist-mediated BBB modulation more efficiently attenuated tumor growth and extended survival than in animal models treated with paclitaxel or temozolomide alone.Conclusion: Thus, image-guided drug delivery following BBB permeability modulation holds promise to enhance the efficacy of chemotherapeutics to glioma.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.