SPECT/CT Image-Based Dosimetry in Radionuclide Tharapy

描述(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，但在这种和其他有针对性的放射性核素疗法中，通过有效的个体化治疗计划来提高疗效还有很大的空间。为了在这一目标上取得进展，必须开发高精度的肿瘤和关键器官(骨髓)剂量测定方法。在目前的应用中，我们将通过开发基于SPECT/CT成像与蒙特卡罗辐射传输计算相结合的新方法来极大地扩展患者特定剂量学的实用性和有效性。最近这种将功能成像与高分辨率解剖成像相结合的系统的临床可用为接近患者特定剂量学开辟了途径，而这些方法在以前的技术中是不可行的。集成成像将配准误差降至最低，并允许将CT测量的肿瘤回归合并到剂量计算中。这两种效应在我们之前的研究中都被证明对肿瘤剂量学有很大的影响。该方法充分利用四维数据集精确计算吸收剂量的空间分布。具体地说，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，以改进重建；2)开发基于体素的肿瘤剂量学方法，将肿瘤回归引入蒙特卡罗辐射传输计算，包括可变形图像配准，以映射变化的肿瘤体素；3)开发基于SPECT/CT图像的骨髓剂量学方法，考虑定量CT确定的骨髓成分的区域差异；4)将这些新方法应用于在集成系统上进行1-131 RIT成像的NHL患者的数据，以确定示踪剂和治疗药代动力学之间的相关性，以及肿瘤剂量反应和骨髓剂量毒性之间的相关性。用新方法获得的关联将与传统的平均剂量计算得到的关联进行比较。有了新的方法，剂量-体积直方图分析和等效均匀剂量等其他更准确地反映吸收剂量反应特性的指标也将被用于剂量反应评估。除了RIT治疗计划的重要性外，这项研究还将在总体上推进剂量学领域的发展。

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.