HGG-40. FOCUSED ULTRASOUND ENHANCES ETOPOSIDE DELIVERY IN A MURINE PONTINE GLIOMA MODEL
| العنوان: | HGG-40. FOCUSED ULTRASOUND ENHANCES ETOPOSIDE DELIVERY IN A MURINE PONTINE GLIOMA MODEL |
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| المؤلفون: | Stergios Zacharoulis, Cheng-Chia Wu, Antonios N. Pouliopoulos, Neil A. Feldstein, Elisa E. Konofagou, Zachary K. Englander, Nina Yoh, Jeffrey N. Bruce, Tony J. C. Wang, Hong-Jian Wei, Masih Tazhibi, Peter Canoll, Nicholas McQuillan |
| المصدر: | Neuro-Oncology |
| بيانات النشر: | Oxford University Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, business.industry, Pontine glioma, Focused ultrasound, Text mining, Oncology, Cancer research, Medicine, AcademicSubjects/MED00300, AcademicSubjects/MED00310, Neurology (clinical), High Grade Gliomas, business, Etoposide, medicine.drug |
| الوصف: | Background Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain cancer with limited treatment options and poor survival. The delivery of systemic therapies in this disease is severely limited by the blood-brain barrier (BBB). Focused ultrasound combined with intravenous microbubbles (FUS+MB) can effectively open the BBB permitting the entry of drugs across the cerebrovasculature. Etoposide is a chemotherapy frequently used in pediatric oncology with well-established anti-tumor effects but limited efficacy when administered systemically in DIPG. Given that FUS+MB in DIPG is not well studied, our goal was to determine the feasibility of ultrasound-mediated BBB opening and etoposide delivery in a preclinical murine pontine glioma model. Methods A syngeneic, orthotopic model was established by stereotactic injection of PDGF-B+PTEN-/-p53-/- murine glioma cells into the pons of B6 albino mice. Mice were randomly divided into control (n=6) or FUS+MB groups (n=6). A single-element, spherical-segment FUS transducer (center frequency=1.5MHz) driven by a function generator through a power amplifier was used with concurrent microbubble injection to sonicate the tumor and its margins on post-injection day 14. Immediately after treatment, 5 mg/kg of intraperitoneal etoposide was administered to all 12 mice. All animals underwent cardiac puncture and blood sampling, followed by transcardiac perfusion and brain harvesting. Liquid chromatography-mass spectometry was performed on both serum and tumor tissue to measure etoposide levels. Results Contrast-enhanced MRI demonstrated successful BBB opening in all FUS+MB mice. Compared to control (mean=20.98ng/g), etoposide concentration in the sonicated tumor tissue (mean=164.77ng/g) was nearly eight times greater. Lastly, the mean brain tumor–to-serum ratio was more than fivefold higher in the treated mice (1.50%) compared with the control mice (0.28%) (P Conclusions FUS+MB is hereby shown successful in BBB opening and enhanced delivery of etoposide in a preclinical pontine glioma model. |
| اللغة: | English |
| تدمد: | 1523-5866 1522-8517 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e5f1965eb36a68f0e81410a0f5cb19c2 http://europepmc.org/articles/PMC8263168 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e5f1965eb36a68f0e81410a0f5cb19c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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