Abstract 4172: Radiation-induced blood-tumor barrier permeability in a preclinical model of lung cancer brain metastasis

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Abstract BACKGROUND: Lung cancer has the highest mortality rate among all cancers and accounts for over half of newly diagnosed brain metastases each year. Standard therapeutic advancements are prolonging lives of lung cancer patients with each new approved formulation, however patients with brain metastases have limited options and no curative measures currently exist. Current treatment modalities for brain metastases from primary lung cancer include differing methodologies of radiotherapy (whole brain radiotherapy and/or stereotactic radiosurgery), systemic chemotherapies, and neurosurgery. Radiation in many cases is not ablative, but palliative. Herein we demonstrate the ability of radiotherapy to influence blood-tumor barrier permeability in a novel preclinical model of lung cancer brain metastasis. METHODS: Athymic female nude mice were intracardially injected with our novel PC-9-BR brain specific lung cancer cell line. Tumors were allowed to develop and monitored using bioluminescent imaging. Using the Xstrahl XenX small animal irradiator, we were able to deliver 26 Gy to the right hemisphere of the immobilized mouse. 4 hours post radiotherapy, mice were perfused with the passive permeability marker Oregon Green, followed by an indocyanine green (bound to albumin) washout to infer vascular space. Brains were then extracted, snap frozen in isopentane (-50°C), and sliced to 20μm. Florescence was quantified using a MVX microscope and cellsense software. RESULTS: Analysis of irradiated brain regions demonstrated statistically significant more accumulation of the passive permeability marker, Oregon Green, compared to the contralateral hemisphere. CONCLUSIONS: Radiation induced permeability was witness in mice after a single dose of 26 Gy when compared to non-irradiated tumor tissue 4 hours post treatment. FURTURE DIRECTIVES: Experiments utilizing ionizing radiation to simulate treatment of CNS metastases could reveal better adjunctive chemotherapeutic regimens and or provide insight to the mechanism underlying this enhanced permeability. Citation Format: Samuel A. Sprowls, Neal Shah, Afroz S. Mohammad, Marc Pinti, Rachel M. Tallman, Devin U. John, Paul R. Lockman. Radiation-induced blood-tumor barrier permeability in a preclinical model of lung cancer brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4172.