Alcocer-Ávila Mario, Levrague Victor, Delorme Rachel, Testa Étienne, Beuve Michaël
Université Claude Bernard Lyon 1, CNRS/IN2P3, IP2I Lyon, UMR 5822, Villeurbanne, France.
University of Grenoble Alpes, CNRS, Grenoble INP, LPSC-IN2P3, Grenoble, France.
Med Phys. 2024 Dec;51(12):9358-9371. doi: 10.1002/mp.17407. Epub 2024 Sep 17.
Targeted radiotherapies with low-energy ions show interesting possibilities for the selective irradiation of tumor cells, a strategy particularly appropriate for the treatment of disseminated cancer. Two promising examples are boron neutron capture therapy (BNCT) and targeted radionuclide therapy with -particle emitters (TAT). The successful clinical translation of these radiotherapies requires the implementation of accurate radiation dosimetry approaches able to take into account the impact on treatments of the biological effectiveness of ions and the heterogeneity in the therapeutic agent distribution inside the tumor cells. To this end, biophysical models can be applied to translate the interactions of radiations with matter into biological endpoints, such as cell survival.
The NanOx model was initially developed for predicting the cell survival fractions resulting from irradiations with the high-energy ion beams encountered in hadrontherapy. We present in this work a new implementation of the model that extends its application to irradiations with low-energy ions, as the ones found in TAT and BNCT.
The NanOx model was adapted to consider the energy loss of primary ions within the sensitive volume (i.e., the cell nucleus). Additional assumptions were introduced to simplify the practical implementation of the model and reduce computation time. In particular, for low-energy ions the narrow-track approximation allowed to neglect the energy deposited by secondary electrons outside the sensitive volume, increasing significantly the performance of simulations. Calculations were performed to compare the original hadrontherapy implementation of the NanOx model with the present one in terms of the inactivation cross sections of human salivary gland cells as a function of the kinetic energy of incident -particles.
The predictions of the previous and current versions of NanOx agreed for incident energies higher than 1 MeV/n. For lower energies, the new NanOx implementation predicted a decrease in the inactivation cross sections that depended on the length of the sensitive volume.
We reported in this work an extension of the NanOx biophysical model to consider irradiations with low-energy ions, such as the ones found in TAT and BNCT. The excellent agreement observed at intermediate and high energies between the original hadrontherapy implementation and the present one showed that NanOx offers a consistent, self-integrated framework for describing the biological effects induced by ion irradiations. Future work will focus on the application of the latest version of NanOx to cases closer to the clinical setting.
低能离子靶向放射疗法为肿瘤细胞的选择性照射展现出了有趣的可能性,这是一种特别适用于治疗播散性癌症的策略。两个有前景的例子是硼中子俘获疗法(BNCT)和使用α粒子发射体的靶向放射性核素疗法(TAT)。这些放射疗法的成功临床转化需要实施精确的辐射剂量测定方法,以便能够考虑离子生物效应以及肿瘤细胞内治疗剂分布的异质性对治疗的影响。为此,生物物理模型可用于将辐射与物质的相互作用转化为生物终点,例如细胞存活。
NanOx模型最初是为预测强子治疗中遇到的高能离子束照射所产生的细胞存活分数而开发的。我们在这项工作中展示了该模型的一种新实现方式,将其应用扩展到低能离子照射,如TAT和BNCT中所发现的离子。
对NanOx模型进行了调整,以考虑初级离子在敏感体积(即细胞核)内的能量损失。引入了额外的假设以简化模型的实际实现并减少计算时间。特别是,对于低能离子,窄轨道近似允许忽略次级电子在敏感体积之外沉积的能量,从而显著提高模拟性能。进行了计算,以比较NanOx模型在强子治疗中的原始实现方式与当前实现方式在人唾液腺细胞失活截面随入射α粒子动能变化方面的情况。
对于高于1 MeV/n的入射能量,NanOx的先前版本和当前版本的预测结果一致。对于较低能量,新的NanOx实现方式预测失活截面会降低,这取决于敏感体积的长度。
我们在这项工作中报告了NanOx生物物理模型的扩展,以考虑低能离子照射,如TAT和BNCT中所发现的离子。在中高能下原始强子治疗实现方式与当前实现方式之间观察到的出色一致性表明,NanOx为描述离子照射诱导的生物效应提供了一个一致的、自我整合的框架。未来的工作将集中于将最新版本的NanOx应用于更接近临床环境的情况。