SPECT/CT Image-Based Dosimetry in Radionuclide Tharapy

描述（由申请人提供）：I-131放射免疫疗法（RIT）在治疗非霍奇金淋巴瘤（NHL）方面显示出巨大的前景，但在这种和其他靶向放射性核素疗法中，通过有效的个体化治疗计划来提高疗效还有很大的空间。为了实现这一目标的进展，它是必要的，高度准确的肿瘤和关键器官（骨髓）剂量测定方法的开发。在本申请中，我们将通过开发基于结合蒙特卡罗辐射传输计算的集成SPECT/CT成像的新方法来极大地扩展患者特定剂量测定的实用性和有效性。这种系统结合了功能成像和高分辨率解剖成像的最新临床可用性为接近患者特定剂量测定开辟了途径，而这在以前的技术中是不可行的。集成成像最大限度地减少配准误差，并允许将CT测量的肿瘤消退纳入剂量计算。这两种效应在我们以前的研究中已经证明对肿瘤剂量测定有很大的影响。所提出的方法充分利用4D数据集，准确地计算吸收剂量的空间分布。具体而言，我们将1）利用CT解剖信息为集成系统实施定量1-131 SPECT方法以改善重建; 2）开发基于体素的肿瘤剂量测定方法，将肿瘤回归纳入Monte Carlo辐射输运计算，包括变形图像配准以映射变化的肿瘤体素; 3）开发基于SPECT/CT图像的骨髓剂量测定法，其考虑了如通过定量CT确定的骨髓组成的区域变化; 4）将这些新方法应用于在集成系统上成像的经历1-131 RIT的NHL患者的数据，确定示踪剂和治疗药代动力学之间的相关性以及肿瘤的剂量反应和骨髓的剂量毒性之间的相关性。将用新方法获得的相关性与传统平均剂量计算获得的相关性进行比较。随着新方法的采用，剂量-体积直方图分析和等效均匀剂量等更准确地反映吸收剂量响应特性的其他测量方法也将用于剂量-响应评价。除了在RIT的治疗计划方面的意义，这项研究将推进剂量学领域的一般。

DESCRIPTION (provided by applicant): I-131 radioimmunotherapy (RIT) is showing great promise in treating non-Hodgkin's lymphoma (NHL), but there is much room for improving efficacy through effective individualized treatment planning in this and other targeted radionuclide therapies. To make advances towards this objective it is imperative that methods be developed for highly accurate tumor and critical organ (bone marrow) dosimetry. In the present application we will greatly expand the utility and effectiveness of patient specific dosimetry by developing new methods based on integrated SPECT/CT imaging coupled to Monte Carlo radiation transport calculation. The recent clinical availability of such systems combining functional imaging with high resolution anatomical imaging has opened avenues for approaching patient specific dosimetry that were not feasible with previous technology. Integrated imaging minimizes registration error and permits incorporation of CTmeasured tumor regression into dosimetry calculations. Both of these effects have been demonstrated in our previous studies to have a large impact on tumor dosimetry. The proposed methods make full use of 4D data sets to accurately calculate spatial distributions of absorbed dose. Specifically, we will 1) implement quantitative 1-131 SPECT methods for the integrated system utilizing CT anatomical information to improve reconstruction; 2) develop a voxel-based approach to tumor dosimetry incorporating tumor regression into the Monte Carlo radiation transport calculation including deformable image registration to map the changing tumor voxels; 3) develop SPECT/CT image based bone marrow dosimetry accounting for regional variations in the marrow composition as determined by quantitative CT; 4) apply these new methods to data from NHL patients undergoing 1-131 RIT imaged on the integrated system, to determine the correlation between tracer and therapy pharmacokinetics and the correlations between dose-response for tumor and dose-toxicity for bone marrow. Correlations obtained with the new methodology will be compared with those obtained from conventional mean dose calculations. With the new methods, other measures that more accurately reflect the response characteristics of absorbed dose, such as dose-volume histogram analysis and equivalent uniform dose, will also be used in the dose-response evaluations. In addition to the significance with regard to treatment planning in RIT, this research will advance the field of dosimetry in general.