Medical Imaging Physics and Radiation Safety, Department of Radiology and Imaging Sciences, University of Utah Health, Salt Lake City, UT 84132, USA.
Department of Radiation Oncology, University of Washington, Seattle, WA 98115, USA.
Cells. 2020 Oct 15;9(10):2302. doi: 10.3390/cells9102302.
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.
准确的剂量测定和硼中子俘获治疗（BNCT）的生物效能的确定具有挑战性，因为在细胞和亚细胞水平存在不同类型和能量的辐射混合。在本文中，我们提出了一个计算的、多尺度的模型系统，以更好地评估几种中子源的相对生物效能（RBE）和复合生物效能（CBE），这些中子源应用于硼中子俘获治疗，使用硼苯丙氨酸（BPA）和一种潜在的单克隆抗体（mAb），该 mAb 用曲妥珠单抗靶向 HER-2 阳性细胞。该多尺度模型通过与硼存在或不存在情况下的体外和体内细胞存活的已发表测量结果进行了测试。联合剂量学和放射生物学模型包括一个分析公式，用于说明中子源的类型、组织或癌症特异性剂量反应特征以及硼的微观分布。该模型与没有硼和有硼的已发表实验结果的对比测试表明，单独使用中子和与硼联合使用时，模型预测的细胞存活与实验确定的细胞存活之间具有良好的一致性。本工作中开发的模型系统对于优化和个体化用于 HER-2 阳性癌症以及可以用 mAb 或常规 BPA 化合物靶向的其他癌症的硼中子俘获治疗具有潜在的应用价值。
