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了接受放射免疫治疗的患者的放射性数量。因此，高活性给药需要介入性操作，而低活性给药可避免骨髓毒性，但可能会以次优治疗为代价。对活跃骨髓的准确剂量测定提供了骨髓毒性的最佳指标，但只有在剂量估计高度针对患者的情况下。这种特异性水平需要单独评估患者骨骼组织中的放射性摄取，以及适当选择放射性核素S的值。S的骨骼剂量测定值目前取自参考曼氏模型，该模型利用单个男性受试者30年前的光学扫描数据。骨骼质量数据来自不同的独立来源，关键研究发表于1926年。最近使用核磁共振显微镜对股骨头和肱骨进行的研究表明，参考男性与女性受试者之间的比例很差，而且不一致。S测量值的准确测量是基于对参考个体和患者的骨骼体积的测量。因此，该项目的具体目标是：(1)使用标称体重指数的身体和放射性核素治疗患者的年龄代表，为成年男性和女性构建详细和全面的参考骨骼模型。有关活体骨骼结构的信息将通过全身CT进行。所有主要骨骼结构的详细剂量测定将通过以下步骤完成：(1)采集骨部位，切片海绵，通过核磁共振显微镜或mieroCT对骨小梁微结构成像，以及辐射传输建模；(2)利用全髋关节置换术患者的骨骼结构的CT分析，验证针对特定患者的S测量值的测量方法。切除的股骨头的恢复和核磁共振显微镜将允许最终验证成比例的患者骨髓剂量测量；(3)评估不同个体之间的海绵体积比率在不同骨骼部位之间的差异程度。其他任务将包括构建骨髓剂量的骨骼内部位剂量-体积直方图，改进的小梁表面模型，以及利用核磁共振显微镜和显微CT图像改进放射性核素治疗中的阿尔法发射体的剂量测定。

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.