Accurate dosimetry and determination of the biological effectiveness of boron neutron capture therapy (BNCT) is challenging because of the mix of different types and energies of radiation at the cellular and subcellular levels. In this paper, we present a computational, multiscale system of models to better assess the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) of several neutron sources as applied to BNCT using boronophenylalanine (BPA) and a potential monoclonal antibody (mAb) that targets HER-2-positive cells with Trastuzumab. The multiscale model is tested against published in vitro and in vivo measurements of cell survival with and without boron. The combined dosimetric and radiobiological model includes an analytical formulation that accounts for the type of neutron source, the tissue- or cancer-specific dose–response characteristics, and the microdistribution of boron. Tests of the model against results from published experiments with and without boron show good agreement between modeled and experimentally determined cell survival for neutrons alone and in combination with boron. The system of models developed in this work is potentially useful as an aid for the optimization and individualization of BNCT for HER-2-positive cancers, as well as other cancers, that can be targeted with mAb or a conventional BPA compound.

中文翻译：

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硼中子俘获疗法相对生物有效性的机理模型

由于在细胞和亚细胞水平上辐射的不同类型和能量的混合，准确的剂量测定法和确定硼中子俘获疗法（BNCT）的生物学有效性具有挑战性。在本文中，我们提出了一种计算的，多尺度的模型系统，以更好地评估使用硼酰苯丙氨酸（BPA）和潜在的单克隆抗体（mAb）应用于BNCT的几种中子源的相对生物有效性（RBE）和复合生物有效性（CBE） ）用曲妥珠单抗靶向HER-2阳性细胞。针对已发布的使用和不使用硼的细胞存活率的体外和体内测量，测试了多尺度模型。剂量学和放射生物学的结合模型包括一个分析公式，该公式说明了中子源的类型，组织或癌症特有的剂量反应特征以及硼的微观分布。针对已发表的有无硼实验的结果对模型进行的测试表明，单独和与硼结合的中子在建模和实验确定的细胞存活率之间具有良好的一致性。这项工作中开发的模型系统可能潜在地有助于优化和个性化BNCT，以治疗可用于mAb或常规BPA化合物的HER-2阳性癌症以及其他癌症。