Guerra Liberal Francisco D C, McMahon Stephen J, Prise Kevin M
The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, United Kingdom.
Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
Biomed Phys Eng Express. 2021 Apr 8;7(3). doi: 10.1088/2057-1976/abf29f.
Due to the increasing clinical application of alpha particles, accurate assessment of their dosimetry at the cellular scale should be strongly advocated. Although observations of the impact of cell and nuclear geometry have been previously reported, this effect has not been fully quantified. Additionally, alpha particle dosimetry presents several challenges and most conventional methodologies have poor resolution and are limited to average parameters across populations of cells. Meaningful dosimetry studies with alpha particles require detailed information on the geometry of the target at a subcellular scale.. The impact of cellular geometry was evaluated for 3 different scenarios, a spherical cell with a concentric nucleus, a spherical cell with an eccentric nucleus and a model of a cell attached to a flask, consisting of a hemispherical oblate ellipsoid, all exposed to 1,700At radionuclide decays. We also evaluated the cross-irradiation of alpha particles as function of distance to a source cell. Finally, a nanodosimetric analysis of absorbed dose to the nucleus of a cell exposed to 1 Gy of different alpha emitting radionuclides was performed.. Simulated data shows the dosimetry of self-absorbed-dose strongly depends on activity localization in the source cell, but that activity localization within the source cell did not significantly affect the cross absorbed dose even when cells are in direct contact with each other. Additionally, nanodosimetric analysis failed to show any significant differences in the energy deposition profile between different alpha particle emitters.. The collected data allows a better understanding of the dosimetry of alpha particles emitters at the sub-cellular scale. Dosimetric variations between different cellular configurations can generate complications and confounding factors for the translation of dosimetric outcomes into clinical settings, but effects of different radionuclides are generally similar.
由于α粒子在临床上的应用日益增加，应大力提倡在细胞尺度上对其剂量学进行准确评估。尽管此前已有关于细胞和细胞核几何形状影响的观察报告，但这种影响尚未得到充分量化。此外，α粒子剂量学存在若干挑战，大多数传统方法分辨率较差，且仅限于细胞群体的平均参数。对α粒子进行有意义的剂量学研究需要亚细胞尺度上目标几何形状的详细信息。针对3种不同情况评估了细胞几何形状的影响，即具有同心细胞核的球形细胞、具有偏心细胞核的球形细胞以及附着在培养瓶上的细胞模型（由半球形扁椭球体组成），所有这些细胞均暴露于1700At放射性核素衰变。我们还评估了α粒子的交叉照射与到源细胞距离的函数关系。最后，对暴露于1 Gy不同α发射放射性核素的细胞细胞核进行了纳米剂量学吸收剂量分析。模拟数据表明，自吸收剂量的剂量学在很大程度上取决于源细胞中的活性定位，但即使细胞彼此直接接触，源细胞内的活性定位对交叉吸收剂量也没有显著影响。此外，纳米剂量学分析未能显示不同α粒子发射体之间在能量沉积分布上有任何显著差异。所收集的数据有助于更好地理解亚细胞尺度上α粒子发射体的剂量学。不同细胞构型之间的剂量学差异可能会给将剂量学结果转化为临床应用带来复杂性和混杂因素，但不同放射性核素的影响通常相似。
