STEM-23. METASTATIC BRAIN TUMOR IMAGING THROUGH TARGETED PEPTIDES ISOLATED VIA PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS

Abstract

Abstract To effectively target metastatic brain tumors (MBTs), the paradigm of initiating treatment against MBTs following detection on clinical imaging needs to be shifted to an understanding of the mechanisms that drive the formation and maintenance of brain metastasis-initiating cells (BMICs). Targeting this tumor sub-population, which may form as a result of activation of the epithelial-mesenchymal transition, may allow for more effective means of understanding and targeting brain metastases. In order to isolate BMICs, we have harvested cells from patient derived MBTs originating from lung cancer and cultured the cells using stem cell media conditions. We then performed in vitro and in vivo phage display biopanning to isolate 12-amino acid length peptides that specifically target BMICs. Several peptides were isolated from both in vitro and in vivo biopanning strategies. Of the peptides recovered, one peptide, LBM4, demonstrated specific binding to MBT cells over primary lung cancer cells in vitro through flow cytometry analysis and immunocytochemistry. Fluorescent tagged LBM4 intravenously injected into mice harboring intracranial brain metastases demonstrated peptide localization to the tumor within the intracranial cavity visualized with live animal imaging. Peptide imaging of tumor corresponded to MRI imaging confirming that the peptides could serve as an alternative to tumor imaging, with the potential for greater sensitivity resulting from the cellular targeting of MBTs. Our results demonstrate that we can use a combination of in vitro and in vivo phage display biopanning to isolate cell specific targeting peptides. MBT targeting peptides can potentially result in a shifting of the clinical treatment paradigm of brain metastases, through the development of more effective targeted therapeutics aimed at BMICs, as well as improving detection of MBT cells which may result in earlier tumor visualization, as well as delineation of tumor recurrence versus radiation effects.