Tissue-directed Implantation Using Ultrasound Visualization for Development of Biologically Relevant Metastatic Tumor Xenografts

Background: Advances in cancer therapeutics depend on reliable in vivo model systems. To develop biologically relevant xenografts, ultrasound was utilized for tissue-directed implantation of neuroblastoma (NB) cell line and patient-derived tumors in the adrenal gland, and for renal subcapsular engraftment of Ewing’s sarcoma (ES). Materials and Methods: NB xenografts were established by direct adrenal injection of luciferase-transfected NB cell lines (IMR32, SH-SY5Y, SK-N-BE2) or NB patient-derived tumor cells (UMNBL001, UMNBL002). ES xenografts were established by renal subcapsular injection of TC32, A673, CHLA-25, or A4573 cells. Progression was monitored by in vivo imaging. Results: Tumors progressed to local disease with metastasis evident by 5 weeks. Metastatic sites included cortical bone, lung, liver, and lymph nodes. Xenografted tumors retained immunochemical features of the original cancer. Conclusion: Human NB adrenal xenografts, including two patient-derived orthotopic, and ES renal subcapsular xenografts were established by ultrasound without open surgery. Tissue-directed implantation is an effective technique for developing metastatic preclinical models.