Liposome Delivery of Boron for BNCT

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DESCRIPTION (provided by applicant): Boron neutron capture therapy (BNCT) is a binary radiation treatment for cancer, which requires the initial selective concentration of the boron-10 isotope within the malignant cells under attack. Subsequent exposure of the tumor volume to thermalized neutrons elicits the cytotoxic [10B(n, a) 7Li] neutron capture reaction, which produces high LET particles in the immediate vicinity of the localized boron-10 target nuclei. As a binary therapeutic approach, BNCT has the potential to provide greater selectivity than either radiation or chemotherapy alone. The overall goal of this proposal is to demonstrate and determine the therapeutic efficacy of BNCT in a small animal model (mice and rats) following boron administration using small unilamellar vesicles (liposomes). Biological studies at the Department of Nuclear Engineering at MIT will examine two liposomal formulations in three different tumor cell lines in mice: murine adenocarcinoma EMT6 (to provide a comparative link to previous studies), and two head and neck tumor models, murine SCCVII and human FaDu. The biodistribution of liposomally delivered boron will be measured, and the cellular microdistribution of boron will be determined. The therapeutic response of the three tumor models will be determined in irradiation experiments at the MIT Reactor; RBE (relative biological effectiveness) and CBE (compound biological effectiveness) factor values will be determined. An in vivo/in vitro tumor cell survival assay will be performed to determine the mechanism of tumor cell killing. The normal tissue response will be quantified in a rat model. The proposed studies will provide the radiobiological data required to decide whether to proceed to large animal or human studies.