Advances in Skeletal Dosimetry Through Microimaging

描述（由申请人提供）：造血活性骨髓的毒性继续限制放射免疫治疗患者的放射性剂量。因此，高活性给药需要介入治疗，而低活性给药避免骨髓毒性，但潜在的代价是次优治疗。准确的活性骨髓剂量测定提供了骨髓毒性的最佳指标，但只有在剂量估计是高度患者特异性的情况下。这种特异性水平需要单独评估患者骨骼组织的活动摄取，以及正确选择放射性核素S值。骨骼剂量学的S值目前是从参考男性模型中获得的，该模型利用了单个男性受试者30年的光学扫描数据。骨骼质量数据来自不同的独立来源，主要研究发表于1926年。最近使用股骨头和肱骨核磁共振显微镜的研究表明，参照男性与女性受试者的比例很差且不一致。S值的精确缩放是基于参考个体和患者的骨骼体积测量。因此，该项目的具体目标是：(1)利用标称身体质量指数的尸体和具有年龄代表性的放射性核素治疗患者的尸体，构建一个详细而全面的成年男性和女性参考骨骼模型。/体内骨骼结构信息将通过全身CT获得。所有主要骨骼结构的详细剂量测定将通过骨部位采集、海绵体切片、通过核磁共振显微镜或显微oct对小梁微观结构进行成像以及辐射传输建模来完成；(2)通过对全髋关节置换术患者骨骼结构的CT分析，验证将S值缩放到特定患者的方法。切除股骨头的恢复和核磁共振显微镜将允许最终验证患者骨髓剂量测定；(3)评估不同个体间海绵体体积比在不同骨骼部位的差异程度。其他任务将包括构建骨髓剂量的骨内剂量-体积直方图，改进小梁表面模型，以及利用核磁共振显微镜和微ct图像改进放射性核素治疗中α -发射器的剂量测定。

DESCRIPTION (provided by applicant): Toxicity of the hematopoietically active bone marrow continues to limit the amount of radioactivity that can be delivered to patients undergoing radioimmunotherapy. High-activity administrations thus demand interventional procedures, while low-activity administrations avoid marrow toxicity but at the potential cost of suboptimal therapy. Accurate dosimetry of the active bone marrow provides the best indicator of marrow toxicity, but only if the dose estimate is highly patient specific. This level of specificity requires separate assessments of activity uptake in the patient's skeletal tissues, as well as the proper selection of radionuclide S values. S values for skeletal dosimetry are currently taken from a Reference Man model that utilizes 30- year-old optical scanning data of a single male subject. Skeletal mass data come from separate and independent sources, with key studies published in 1926. Recent studies using NMR microscopy of the femoral head and humerus have shown that scaling of Reference Man to female subjects is poor and inconsistent. Accurate scaling of S values is based on measurements of skeletal volumes in both a reference individual and in the patient. Consequently, the project Specific Aims are: (1) to construct a detailed and comprehensive reference skeletal model for the adult male and female using cadavers of nominal body mass index and an age representative of radionuclide therapy patients. /nformation on in-vivo skeletal structure will be made via whole-body CT. Detailed dosimetry for all major skeletal structures will be accomplished through bone site harvesting, sectioning of spongiosa, imaging of the trabecular microstructure through either NMR microscopy or mieroCT, and radiation transport modeling; (2) to verify methods of scaling S values to specific patients using CT analyses of skeletal structure in patients scheduled for total hip arthroplasty. Recovery and NMR microscopy of the excised femoral heads will permit final verification of scaled patient marrow dosimetry; (3) to assess the degree to which ratios of spongiosa volumes between different individual varies among difference skeletal sites. Additional tasks will include the construction of intra-skeletal-site dose-volume histograms of marrow dose, improved models of the trabecular surfaces, and improved dosimetry for alpha-emitters in radionuclide therapy utilizing the NMR microscopy and microCT images.