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α粒子微剂量学

Alpha-particle microdosimetry.

作者信息

Chouin Nicolas, Bardies Manuel

机构信息

Department of Radiation Physics, The Sahlgrenska Academy at the University of Gothenburg, Sweden.

出版信息

Curr Radiopharm. 2011 Jul;4(3):266-80. doi: 10.2174/1874471011104030266.

Abstract

With the increasing availability of alpha emitters, targeted α-particle therapy has emerged as a solution of choice to treat haematological cancers and micrometastatic and minimal residual diseases. Alpha-particles are highly cytotoxic because of their high linear energy transfer (LET) and have a short range of a few cell diameters in tissue, assuring good treatment specificity. These radiologic features make conventional dosimetry less relevant for that context. Stochastic variations in the energy deposited in cell nuclei are important because of the microscopic target size, low number of α- particle traversals, and variation in LET along the α-particle track. Microdosimetry provides a conceptual framework that aims at a systematic analysis of the stochastic distribution of energy deposits in irradiated matter. The different quantities of microdosimetry and the different methods of microdosimetric calculations were described in the early eighties. Since then, numerous models have been published through the years and applied to analyse experimental data or to model realistic therapeutic situations. Major results have been an accurate description of the high toxicity of α-particles, and the description of the predominant effect of activity distribution at the cellular scale on toxicity or efficacy of potential targeted α-particle therapies. This last factor represents a major limitation to the use of microdosimetry in vivo because determination of the source - target distribution is complicated. The future contributions of microdosimetry in targeted α-particle therapy research will certainly depend on the ability to develop high-resolution detectors and on the implementation of pharmaco-kinetic models at the tumour microenvironment scale.

摘要

随着α发射体的可获得性不断增加,靶向α粒子疗法已成为治疗血液系统癌症以及微转移和微小残留疾病的首选解决方案。α粒子因其高线性能量传递(LET)而具有高度细胞毒性,并且在组织中的射程仅为几个细胞直径,从而确保了良好的治疗特异性。这些放射学特征使得传统剂量学在此背景下不太适用。由于微观靶标尺寸、α粒子穿过次数少以及沿α粒子轨迹的LET变化,细胞核中沉积能量的随机变化很重要。微剂量学提供了一个概念框架,旨在系统分析辐照物质中能量沉积的随机分布。微剂量学的不同量和微剂量计算的不同方法在20世纪80年代初就有描述。从那时起,多年来已经发表了许多模型,并应用于分析实验数据或模拟实际治疗情况。主要成果包括准确描述了α粒子的高毒性,以及描述了细胞尺度上活性分布对潜在靶向α粒子疗法的毒性或疗效的主要影响。最后一个因素是体内使用微剂量学的主要限制,因为源 - 靶标分布的确定很复杂。微剂量学在靶向α粒子疗法研究中的未来贡献肯定将取决于开发高分辨率探测器的能力以及在肿瘤微环境尺度上实施药代动力学模型的能力。

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