Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases.
Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases.
复制标题
DOI：
10.7150/thno.22217
复制
发表时间：
2018
期刊：
影响因子：
12.4
通讯作者：
Vallis KA
中科院分区：
文献类型：
--
作者：
Falzone N;Ackerman NL;Rosales LF;Bernal MA;Liu X;Peeters SG;Soto MS;Corroyer-Dulmont A;Bernaudin M;Grimoin E;Touzani O;Sibson NR;Vallis KA
脑转移常发生在乳腺癌患者中，这是一个紧迫的治疗挑战。血管细胞黏附分子-1(VCAM-1)在脑转移瘤早期表达上调，为早期脑转移瘤的发现和治疗提供了靶点。本研究的目的是利用早期脑转移模型来评价α放射性核素(149Tb、211At、212Pb、213Bi和225Ac)、β放射性核素(90Y、161Tb和177Lu)和俄歇电子(AE)发射体67Ga、89Zr、111In和124I对放射性核素靶向治疗的疗效。方法：使用Geant4通用蒙特卡罗(MC)工具包和Geant4-DNA低能物理模型，对小鼠脑实质进行组织切片和双光子显微镜观察。能量沉积被评估为径向函数，所产生的相空间被叠加在DNA模型上，以估计典型的β-和α-发射体177Lu和212Pb的双链断裂产额。相对生物有效性(RBE)值仅通过评估物理相互作用造成的DNA损伤来确定。结果：177Lu每GbpGy2.6 9±0.0 8DSB产额，从管腔到半径10 0µm无明显变化，2 12Pb2 12Pb2 1 MeV和8.8 MeVα衰变产物产生的局部最大值分别为7.6 4±0.12和9.15±0.2 4。鉴于其较高的DSB产率，212Pb在早期微转移灶的短程靶向方面可能比177Lu更有效。结论：对早期脑转移模型的MC模拟对α-，β和AE发射的放射性核素治疗TRT的潜在疗效提供了宝贵的见解。~(212)Pb由于可用于SPECT显像，具有抗辐射核素的性质，具有良好的剂量分布和相对生物效应。
Brain metastases develop frequently in patients with breast cancer, and present a pressing therapeutic challenge. Expression of vascular cell adhesion molecule 1 (VCAM-1) is upregulated on brain endothelial cells during the early stages of metastasis and provides a target for the detection and treatment of early brain metastases. The aim of this study was to use a model of early brain metastasis to evaluate the efficacy of α-emitting radionuclides, 149Tb, 211At, 212Pb, 213Bi and 225Ac; β-emitting radionuclides, 90Y, 161Tb and 177Lu; and Auger electron (AE)-emitters 67Ga, 89Zr, 111In and 124I, for targeted radionuclide therapy (TRT). METHODS: Histologic sections and two photon microscopy of mouse brain parenchyma were used to inform a cylindrical vessel geometry using the Geant4 general purpose Monte Carlo (MC) toolkit with the Geant4-DNA low energy physics models. Energy deposition was evaluated as a radial function and the resulting phase spaces were superimposed on a DNA model to estimate double-strand break (DSB) yields for representative β- and α-emitters, 177Lu and 212Pb. Relative biological effectiveness (RBE) values were determined by only evaluating DNA damage due to physical interactions. RESULTS: 177Lu produced 2.69 ± 0.08 DSB per GbpGy, without significant variation from the lumen of the vessel to a radius of 100 µm. The DSB yield of 212Pb included two local maxima produced by the 6.1 MeV and 8.8 MeV α-emissions from decay products, 212Bi and 212Po, with yields of 7.64 ± 0.12 and 9.15 ± 0.24 per GbpGy, respectively. Given its higher DSB yield 212Pb may be more effective for short range targeting of early micrometastatic lesions than 177Lu. CONCLUSION: MC simulation of a model of early brain metastases provides invaluable insight into the potential efficacy of α-, β- and AE-emitting radionuclides for TRT. 212Pb, which has the attributes of a theranostic radionuclide since it can be used for SPECT imaging, showed a favorable dose profile and RBE.