Liposome Delivery of Boron for BNCT

描述(申请人提供)：硼中子俘获疗法(BNCT)是一种治疗癌症的二元放射疗法，它需要在受到攻击的恶性细胞内对硼-10同位素进行初始选择性浓缩。随后将肿瘤体积暴露于加热的中子，引发细胞毒性[10B(n，a)7Li]中子俘获反应，在局部B-10靶核附近产生高LET粒子。作为一种二元治疗方法，BNCT有可能提供比单纯放疗或化疗更大的选择性。这项建议的总体目标是在小动物模型(小鼠和大鼠)中展示和确定BNCT的治疗效果，该模型使用小的单层囊泡(脂质体)给药。麻省理工学院核工程系的生物学研究将在小鼠的三种不同肿瘤细胞系中检查两种脂质体制剂：鼠腺癌EMT6(为之前的研究提供比较链接)，以及两种头颈部肿瘤模型，小鼠SCCVII和人FaDu。将测量脂质体输送的硼的生物分布，并将测定硼的细胞微观分布。三种肿瘤模型的治疗反应将在MIT反应堆的辐射实验中确定；将确定RBE(相对生物有效性)和CBE(复合生物有效性)因子值。将进行体内/体外肿瘤细胞存活实验，以确定肿瘤细胞的杀伤机制。正常的组织反应将在大鼠模型中进行量化。拟议的研究将提供所需的放射生物学数据，以决定是否继续进行大型动物或人体研究。

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.