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.
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