Targeted alpha therapy with 212Pb or 225Ac: Change in RBE from daughter migration
Targeted alpha therapy with 212Pb or 225Ac: Change in RBE from daughter migration
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DOI：
10.1016/j.ejmp.2018.05.020
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发表时间：
2018-07-01
影响因子：
3.4
通讯作者：
Bernal, Mario A.
中科院分区：
文献类型：
--
作者：
Ackerman, Nicole L.;Rosales, Liset de la Fuente;Bernal, Mario A.
靶向α治疗（达特）可以早期提供给脑转移风险高的患者，靶向肿瘤细胞渗透到脑中的血管系统区域。我们已经利用了一个Monte Carlo模型表示脑血管系统计算物理剂量和DNA损伤的α-发射器Ac-225和Pb-212。所有放射性衰变产物的微米级剂量分布在Geant 4中建模，包括使用Geant 4-DNA模型的eV级相互作用。然后将这些相互作用叠加在原子尺度DNA模型上以估计链断裂产率。除了Ac-225具有比Pb-212更高的每次衰变剂量之外，它还具有是Pb-212的4.7 +/-0.5倍的每次衰变的双链断裂产率。然而，这两种核素的疗效取决于将子核保留在脑血管系统中的靶位置。当包括整个衰变链时，Ac-225和Pb-212的相对生物有效性（RBE）相似，最大值分别为2.7 +/- 0.6和2.5 +/- 0.5，RBE值约为2至80 μ m深度。如果初始子体丢失，Pb-212的RBE完全降低到1或更低，Ac-225的RBE仅在前40 μ m约为2。
Targeted alpha-therapy (TAT) could be delivered early to patients who are at a high-risk for developing brain metastases, targeting the areas of the vasculature where tumor cells are penetrating into the brain. We have utilized a Monte Carlo model representing brain vasculature to calculate physical dose and DNA damage from the a-emitters Ac-225 and Pb-212. The micron-scale dose distributions from all radioactive decay products were modeled in Geant4, including the eV-scale interactions using the Geant4-DNA models. These interactions were then superimposed on an atomic-scale DNA model to estimate strand break yields. In addition to Ac-225 having a higher dose per decay than Pb-212, it also has a double strand break yield per decay that is 4.7 +/- 0.5 times that of Pb-212. However, the efficacy of both nuclides depends on retaining the daughter nuclei at the target location in the brain vasculature. The relative biological effectiveness (RBE) of Ac-225 and Pb-212 are similar when the entire decay chains are included, with maxima of 2.7 +/- 0.6 and 2.5 +/- 0.5 (respectively), and RBE values of about 2 to a depth of 80 mu m. If the initial daughter is lost, the RBE of Pb-212 is completely reduced to 1 or lower and the RBE of Ac-225 is approximately 2 only for the first 40 mu m.