Assessment of Focused Ultrasound Mediated Delivery of Chemotherapy and Cytotoxic Activity in Brain Tumors with Cancer Soluble Biomarkers
Author(s)
Menezes, Victor
Advisor(s)
Arvanatis, Costas
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Abstract
Microbubble enhanced focused ultrasound (MB-FUS) is a promising minimally invasive technology for targeted drug delivery in brain tumors. As this technology is currently under clinical evaluation, methods to assess effective drug delivery and refine treatment protocols, beyond the anatomical information (e.g., tumor size) provided by MRI, are needed. In this study, we investigated the abilities of cancer soluble molecules to assess effective chemotherapy agent delivery in glioma tumors, track tumor growth, and confirm blood-brain and blood-tumor barrier (BBB/BTB) opening. We employed the glioblastoma cell line GL261 that was transfected to express the secretable bioluminescent molecule Gaussia luciferase (GLuc), which was used as a test molecule for assay development. We separately applied three different chemotherapeutic agents (Doxorubicin, Carboplatin, Temozolomide), which are currently in clinical trials in combination with MB-FUS and assessed the secretion of GLuc molecule and gene (cell-free DNA – cfDNA), using bioluminescence assay and polymerase chain reaction (PCR) assays, including real-time PCR (rtPCR) and droplet-digital PCR (ddPCR). Our in vitro and preliminary in vivo analysis and quantification of soluble cancer biomarkers suggest that cfDNA can be employed to assess effective chemotherapy (i.e., doxorubicin) delivery to aggressive brain tumors, such as glioblastoma, however these approaches might not be as effective with all types of chemotherapy (i.e., carboplatin). Further research to assess the potential of cfDNA to monitor effective chemotherapy delivery in brain tumors using MB-FUS is warranted.
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Date
2022-07-29
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