Focused Ultrasound Facilitated Concurrent Large-Molecular Antibody and Chemo-Drug Delivery for Brain Tumor Treatment

Glioblastoma multiforme (GBM) is the most common brain tumor with irregular blood vessels, extensive vascular proliferation, increased expression of angiogenic factors. Patients have a 5-year survival rate under 5%, the major reason is highly vascularization and the exist of blood-brain barrier (BBB). Focused ultrasound (FUS) has been discovered can be utilized for localized and transient BBB disruption in brain tissue, which opens the opportunity for local drug delivery into brain (Currently 98% of drugs cannot penetrate into brain). Currently the MR imaging is the most common used tool for FUS-mediated drug delivery evaluation, but it cannot monitor the drug delivery and distribution. Positron emission tomography (PET) is a reliable functional imaging tool for the drug efficiency validation with various radioactive tracers, it can apply to innovative drug development, treatment following and prognosis prediction. The combination of FUS and targeting PET tracer will be a potential application to cancer therapy. The aim of this proposal intends to extend our technology to develop an optimal focused ultrasound drug delivery system by screening various parameters including acoustic intensity, pulse length, different sizes of microbubble, which can enhance and facilitate a blood-brain barrier (BBB) opening for local anti-angiogenesis antibody or chemo-drug release in the brain. This platform can not only deliver radio-labeled antibody into brain to achieve targeted therapy, the in vivo distribution and PK/PD of the drug can be also monitored and evaluated. In addition, the results of this study can provide an important reference for clinical treatment planning in the future. This project will run in two years, which in the 1st year for system establishment and in the 2nd year for drug development challenges to traditional chemo-drug, delivery efficiency validation, preclinical evaluation and feasibility testing with multiple function molecular drug, and will apply on the tumor-bearing small animals. Expected outcomes includes: (1) Scientific output (at least 1 SCI journal and 2 international conference publish), (2) at least 4 professional training can be cultivated through the execution of this project and provide chance to enter global medicine and medical device market.

Project ID:PB10507-2950
External Project ID:MOST105-2221-E182-004-MY2