Using In Vivo Fluorescence Angiography to Evaluate the Impact of Small Molecule Anti-Metastatic Inhibitors of Osteosarcoma

Despite multiple advances in cancer therapy, osteosarcoma survival remains heavily dependent upon the existence of metastatic disease at the time of diagnosis. Patients with non-metastatic osteosarcoma have a survival rate of nearly 70%, which declines to levels as low as 15% once metastatic disease to the lungs is detected. The lack of new effective therapies for this disease lies in the lack of pre-clinical models that evaluate metastatic osteosarcoma, rather than primary tumors. Further, no effective methodology for in vivo quantitative tumor and lung metastatic imaging has been developed, which may in turn help us characterize the benefits of small molecule pathway inhibition therapies in isolation and in concert. Here we propose to validate a novel immunocompetent osteosarcoma mouse model that has been developed by our group. To do so, we will also elaborate upon the promising potential of indocyanine green dye angiography as an in vivo quantitative monitoring tool for primary tumor and lung metastasis measurements in our model. Finally, we will begin early pilot trials of small molecular inhibition of aldehyde dehydrogenase and the Notch pathway, which we have implicated in vitro as critical factors related to osteosarcoma growth and metastasis. Findings will be used to support larger grant proposals to aid in the translation of novel drugs to clinical use.