A major asset in the use of radiolabeled antibodies is the ability to trace the agent in vivo and readily generate pharmacokinetic and radiation dosimetric information that can guide development of the therapeutic agents, define conditions for their optimal use, and serve as the basis for individualized treatment planning. The primary role of this core is to support the clinical trials in Projects 1 and 2 and the translational chemistry, radiochemistry and radiopharmaceutical development conducted in Project 3 and Core C by providing pharmacokinetic and dosimetric information for decision-making. Dosimetric support for preclinical studies in Projects 1 and 2 is also provided. Methodology and software have been developed that converts regional counts obtained by quantitative imaging or biodistribution studies to macroscopic tissue radiation doses; these estimates have been validated. Pharmacokinetic and dosimetric data for a variety of antibody-based radiopharmaceuticals has been generated and has served as the basis for the evolution to the proposed use of DOTA-peptide radiopharmaceuticals because of their unusually favorable therapeutic index. In order to fulfill past requirements, methods for quantitative imaging, region of interest and background definition, and attenuation and coincidence correction have been implemented. Because the proposed protocols need to push tumor radiation to the maximum in order to attempt to fulfill the goal of curative radioimmunotherapy, treatment planning requires implementation of patient-specific dosimetry that accounts for major tissues that may be dose-limiting. This requires additional refinements to existing methods in order to further account for source depth, tissue overlapping, anatomic location and volume effects, radionuclide energy distribution, and non-uniform radionuclide deposition, etc. The goal is to develop a comprehensive radioimmunotherapy planning System based on patient-specific dosimetry and tissue dose response function.
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