BMET-40: NANO PLATFORM FOR DYNAMIC IN VIVO TRACKING OF NEURAL STEM CELLS TO BRAIN METASTASES OF BREAST CANCER

INTRODUCTION: Brain metastases of breast cancer (BMBC) are the leading cause of brain malignancy and mortality in women with limited therapeutic options. Recent innovations by our group have demonstrated a novel BMBC-targeted therapeutic modality utilizing a human neural stem cell (hNSC) line approved by FDA for glioblastoma multiforme (GBM) therapy. Here we report a nano tracing strategy to expand the therapeutic scope of hNSCs by incorporating Mesoporous Silica Nanoparticles (MSNs) labeled with radioisotopes for Single Photon Emission Computed Tomography (SPECT), thus establishing the feasibility of real-time tracking of therapeutic hNSCs in preclinical models of BMBC, and enabling the multifaceted theranostic platform. METHODS: To establish brain metastasis models, intracardiac injection of metastatic breast cancer cells (MDA-MB231-BrM2 expressing firefly luciferase/fluc; 2.5x10⁵ cells/200 µl PBS) was performed in female nude mice. Weekly bioluminescence imaging (BLI) was done to track the development of BMBC. MSNs were synthesized and radiolabeled with ¹¹¹In for hNSC loading and SPECT imaging. Labeled hNSCs were then delivered either locally via intracranial microinjection (5x10⁵ cells) or systemically via intracardiac injection (3x10⁶ cells). MicroSPECT/CT imaging was performed for tracking NSCs at various time points. The brains were then collected and processed for histology and immunocytochemistry verification. RESULTS: In the intracranial models, SPECT/CT shows dynamic migration of ¹¹¹In-MSN-labeled hNSCs towards the strong fluc+ BMBC. The distribution patterns of NSCs reflects those of BMBC. In the systemic models, effective extravasation of hNSCs from circulation to BMBC sites 48 h after injection was also confirmed. CONCLUSIONS: We demonstrate a novel nano material-based strategy to achieve sensitive and real-time tracking of migratory hNSCs targeting BMBC. Integration of multi-modal imaging co-registration allowing for simultaneous visualization of BMBC and stem cells will greatly enhance our knowledge of the behaviors of therapeutic stem cells in the brain.