Redefining Relative Biological Effectiveness in the Context of the EQDX Formalism: Implications for Alpha-Particle Emitter Therapy
Redefining Relative Biological Effectiveness in the Context of the EQDX Formalism: Implications for Alpha-Particle Emitter Therapy
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DOI：
10.1667/rr13483.1
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发表时间：
2014-01-01
影响因子：
3.4
通讯作者：
Sgouros, George
中科院分区：
文献类型：
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作者：
Hobbs, Robert F.;Howell, Roger W.;Sgouros, George
α粒子放射性药物治疗（α RPT）目前正受到越来越多的关注，作为一个可行的替代化疗的目标播散性微转移性疾病。理论上，α RPT可以通过治疗前成像和剂量测定进行个性化。然而，在实践中，鉴于α粒子排放的特殊性，尚未报告准确预测器官毒性阈值的剂量测定方法。这部分是由于α粒子辐射引起的生物效应与传统的外部束（光子或电子）辐射或β粒子发射放射性药物引起的效应明显不同。相对生物有效性（RBE）的概念用于量化α粒子与参考辐射（通常是β发射体或外部束辐射）实现给定生物反应所需的吸收剂量比。然而，如传统定义的，RBE作为吸收剂量的函数而变化，因此单个RBE值在其效用上是有限的，因为它不能用于预测在宽范围的吸收剂量上的响应。因此，正在努力使核医学和外射束放射治疗的不同分割方案和剂量率的生物效应模型标准化。鉴于在癌症治疗中，与核医学相比，外部辐射束的使用占优势，ICRU最近提出了更临床相关的量，即2戈伊等效剂量EQD 2（α/β）。与EQD 2（α/β）一致，我们引入了一个新的，重新定义的RBE量，命名为RBE 2（α/β），作为表征粒子吸收剂量响应曲线和低LET兆伏光子2戈伊分数等效剂量响应曲线的两个线性系数的比值。沿着提出了新的形式主义的理论框架，其应用程序从照射的乳腺癌细胞系获得的实验数据。放射生物学参数获得使用线性二次模型，以适应细胞存活数据的MDA-MB-231人乳腺癌细胞照射的粒子或低LET Cs-137 γ射线的单一部分。从这些，生物学有效剂量（BED）和EQD 2（α/β）响应线的线性系数推导出分次照射。标准RBE计算，使用传统的单一分数参考辐射，给出的RBE值范围为2.4（存活分数为0.82）-6.0（存活分数为0.02），而所有存活分数值的剂量无关RBE 2（4.6）值为4.5。此外，RBE 2（α/β）和EQD 2（α/β）的生物效应建模表明，有能力预测急性和分级低LET辐射，α粒子和慢性指数下降剂量率的低LET辐射照射的细胞存活分数。RBE 2型（α/β）与α粒子发射体的吸收剂量无关，它为数据报告和等效剂量转换提供了一个比传统的依赖剂量的RBE定义更合理的框架，而且，它为α粒子剂量学范式的持续发展提供了一个急需的基础，并将促进使用来自外射束放射治疗的耐受剂量数据，从而有助于开发α RPT作为单一形式以及用于组合疗法。(C)2014年，辐射研究学会
Alpha-particle radiopharmaceutical therapy (alpha RPT) is currently enjoying increasing attention as a viable alternative to chemotherapy for targeting of disseminated micrometastatic disease. In theory, alpha RPT can be personalized through pre-therapeutic imaging and dosimetry. However, in practice, given the particularities of alpha-particle emissions, a dosimetric methodology that accurately predicts the thresholds for organ toxicity has not been reported. This is in part due to the fact that the biological effects caused by alpha-particle radiation differ markedly from the effects caused by traditional external beam (photon or electron) radiation or beta-particle emitting radiopharmaceuticals. The concept of relative biological effectiveness (RBE) is used to quantify the ratio of absorbed doses required to achieve a given biological response with alpha particles versus a reference radiation (typically a beta emitter or external beam radiation). However, as conventionally defined, the RBE varies as a function of absorbed dose and therefore a single RBE value is limited in its utility because it cannot be used to predict response over a wide range of absorbed doses. Therefore, efforts are underway to standardize bioeffect modeling for different fractionation schemes and dose rates for both nuclear medicine and external beam radiotherapy. Given the preponderant use of external beams of radiation compared to nuclear medicine in cancer therapy, the more clinically relevant quantity, the 2 Gy equieffective dose, EQD2(alpha/beta), has recently been proposed by the ICRU. In concert with EQD2(alpha/beta), we introduce a new, redefined RBE quantity, named RBE2(alpha/beta), as the ratio of the two linear coefficients that characterize the a particle absorbed dose-response curve and the low-LET megavoltage photon 2 Gy fraction equieffective dose-response curve. The theoretical framework for the proposed new formalism is presented along with its application to experimental data obtained from irradiation of a breast cancer cell line. Radiobiological parameters are obtained using the linear quadratic model to fit cell survival data for MDA-MB-231 human breast cancer cells that were irradiated with either a particles or a single fraction of low-LET Cs-137 gamma rays. From these, the linear coefficient for both the biologically effective dose (BED) and the EQD2(alpha/beta) response lines were derived for fractionated irradiation. The standard RBE calculation, using the traditional single fraction reference radiation, gave RBE values that ranged from 2.4 for a surviving fraction of 0.82-6.0 for a surviving fraction of 0.02, while the dose-independent RBE2(4.6) value was 4.5 for all surviving fraction values. Furthermore, bioeffect modeling with RBE2(alpha/beta) and EQD2(alpha/beta) demonstrated the capacity to predict the surviving fraction of cells irradiated with acute and fractionated low-LET radiation, alpha particles and chronic exponentially decreasing dose rates of low-LET radiation. RBE2(alpha/beta) is independent of absorbed dose for alpha-particle emitters and it provides a more logical framework for data reporting and conversion to equieffective dose than the conventional dose-dependent definition of RBE.Moreover, it provides a much needed foundation for the ongoing development of an alpha-particle dosimetry paradigm and will facilitate the use of tolerance dose data available from external beam radiation therapy, thereby helping to develop alpha RPT as a single modality as well as for combination therapies. (C) 2014 by Radiation Research Society