Using nanobubble contrast-enhanced ultrasound imaging to assess tumoral microenvironment characteristics and relate them to therapeutic efficacy

Tumors are complex and heterogeneous. This can make them difficult to treat, especially when a therapy may ultimately only reach part of the tumor due to physical microenvironment barriers. Nanoparticle-based therapies often rely on the enhanced permeability and retention effect as the primary strategy for the accumulation of nanoparticles at the tumor site. However, this concept is controversial and it does not work as well in humans as it does in animal studies. A method to non-invasively gain a better understanding of the entire heterogeneous tumor microenvironment could be key to improving patient treatment and overall outcomes. This study has two primary aims. 

     

1. Use nanobubble-contrast enhanced ultrasound to stratify tumor microenvironment characteristics, such as vascular permeability. This study is conducted in mice with subcutaneous tumors of two cell lines (a glioblastoma and a colorectal adenocarcinoma) that grow solid tumors with vastly different vascular permeability potential and vascular endothelial cell integrity. The goal is to use nanobubble imaging to differentiate the tumors and try to determine their potential for nanoparticle extravasation, validated through histology. 

     

2. Predict which tumors will respond to therapy most effectively by using the parameters identified in aim 1. This study uses what we learned about the tumor microenvironment with nanobubble contrast-enhanced ultrasound imaging and applies it to therapeutic efficacy. An ovarian adenocarcinoma is evaluated with nanobubble imaging and then a nanoparticle-based treatment is injected intravenously into the mice. The tumor size is then monitored over time and compared to the predictions based on the nanobubble contrast-enhanced ultrasound imaging results. 

 

For more information on this project contact michaela.cooley@case.edu