A novel brain metastasis xenograft model for convection-enhanced delivery of targeted toxins via a micro-osmotic pump system enabled for real-time bioluminescence imaging

Brain metastasis is a common cause of mortality in patients with cancer, and is associated with poor prognosis. There is a current requirement for the identification of relevant brain metastasis tumor models, which may be used to test novel therapeutic agents and delivery systems in pre-clinical studies. The present study aimed to investigate the development of a murine model of brain metastasis, and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to targeted toxins (TT). A luciferase-modified human brain metastasis cell line was implanted into the caudate-putamen of athymic mice using a stereotactic frame. Tumor growth was monitored by BLI, and tumor volume was calculated from three-dimensional measurements of serial histopathological sections. Histopathological analyses revealed the presence of tumor growth within the caudate-putamen of all of the mice, and BLI was shown to be correlated with tumor volume. To evaluate whether this model would allow the detection of a therapeutic response, mice bearing metastatic brain tumor cell xenografts were treated with TT delivered by convection-enhanced delivery (CED), via a micro-osmotic pump system. The TT-treated groups were submitted to metastatic brain tumor cell experiments, the results of which suggested that TT treatment delayed tumor growth, as determined by BLI monitoring, and significantly extended the survival of the mice. The results of the present study demonstrated the efficacy of a brain metastasis model for CED of TT via a micro-osmotic pump system in athymic mice, in which tumor growth and response to therapy were accurately monitored by BLI. In conclusion, this model may be well-suited for pre-clinical testing of potential therapeutics for the treatment of patients with metastatic brain tumors.