Advisor:

Costas Arvanitis, PhD

Committee Members:

John McDonald, PhD

Levi Wood, PhD

Assessment of Chemotherapy Cytotoxic Activity in Brain Tumors with Cancer Soluble Biomarkers

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, using bioluminescence assay and PCR. Our analysis and quantification of soluble cancer biomarkers suggest that cfDNA can be employed to assess effective chemotherapy delivery to brain cancer, however these approaches might not be as effective with all types of chemotherapy. Further research to assess the potential of cfDNA to monitor effective chemotherapy delivery in brain tumors using MB-FUS is warranted.