Xu T, Liu T, Li G, Dugal C, Aydemir N A, Liu Y, Roeske J C
Canadian Nuclear Laboratories, Chalk River, ON, K0J 1J0, Canada.
Department of Electrical and Computer Engineering, Clarkson University, Potsdam, NY, 13699, USA.
Med Phys. 2020 Jun;47(6):2550-2557. doi: 10.1002/mp.14111. Epub 2020 Mar 31.
To predict biological effects of targeted alpha therapy (TAT) in preclinical studies, dosimetry calculations based on the micro-level distributions of emitters are essential. Due to the saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha-immuno-conjugate and decay daughters may inevitably be transported by convection and diffusion along with blood or lymphatic circulation. This results in highly nonuniform and unsteady distributions of irradiation sources. Since the micro-level distribution of emitters cannot be measured and obtained in patients with current technology, a modeling toolset to give more insight of the internal dose could be an alternative.
A multi-physics model based on a Monte Carlo microdosimetry technique and computational fluid dynamics (CFD) modeling was developed and applied to multiple internal irradiation sources. The CFD model tracks the path of the radionuclides and the dose model is capable of evaluating the time-dependent absorbed dose to the target.
The conceptual model is capable of handling complex nonuniform irradiation sources in vasculature. The results from the simulations indicate that the assumption of homogeneous and motionless distribution of the administered activity used in the conventional dose calculation tends to significantly underestimate or overestimate the absorbed dose to the vascular system in various scenarios.
Modeling the in vivo transport of radionuclides has the potential to improve the accuracy of TAT dose estimates. It could be the first step to develop a simulation tool set for assessing absorbed dose to tumor or normal tissues and predict the corresponding biological responses in the future.
在临床前研究中预测靶向α治疗（TAT）的生物学效应时，基于发射体微观水平分布的剂量学计算至关重要。由于肿瘤抗原位点的饱和以及衰变导致的键断裂，一些α免疫缀合物及其衰变产物可能不可避免地随血液或淋巴循环通过对流和扩散进行转运。这导致辐射源的分布高度不均匀且不稳定。由于目前的技术无法在患者体内测量和获取发射体的微观水平分布，因此一种能更深入了解内部剂量的建模工具集可能是一种替代方法。
开发了一种基于蒙特卡罗微剂量学技术和计算流体动力学（CFD）建模的多物理模型，并将其应用于多个内部辐射源。CFD模型追踪放射性核素的路径，剂量模型能够评估靶区随时间变化的吸收剂量。
该概念模型能够处理脉管系统中复杂的非均匀辐射源。模拟结果表明，传统剂量计算中使用的给药活度均匀且静止分布的假设在各种情况下往往会显著低估或高估脉管系统的吸收剂量。
对放射性核素的体内转运进行建模有可能提高TAT剂量估计的准确性。这可能是未来开发用于评估肿瘤或正常组织吸收剂量并预测相应生物学反应的模拟工具集的第一步。
