Establishing Human and Canine Xenograft Murine Osteosarcoma Models for Application of Focused Ultrasound Ablation.

Osteosarcoma (OS) is the most commonly occurring type of bone cancer in both humans and canines. The survival outcomes for OS patients have not improved significantly in decades. A novel and innovative treatment option that is currently under investigation for OS in the veterinary field is the focused ultrasound ablation modality, histotripsy. Histotripsy is a non-thermal, non-invasive, non-ionizing ablation modality that destroys tissue through generation of acoustic cavitation. In the current study, we sought to investigate the utility of an orthotropic OS xenograft murine model for characterization of chronic ablative and clinical outcomes post-histotripsy ablation. Given the high comparative relevance of canine to human OS, histotripsy was delivered to orthotopic OS tumors in both human and canine xenograft murine models. Histotripsy improved limb function in tumor-bearing mice compared to untreated tumor bearing mice. The results of this study demonstrated the utility of the orthotopic OS xenograft murine model for histotripsy-based preclinical studies. The current study is the first published investigation for the use of an orthotopic xenograft murine model for the development of histotripsy ablation for OS. The developmental process of the model, technical limitations, and future directions are discussed.