This project will advance the use of computerized dosimetric models during the pre-clinical phase of radiopharmaceutical development. Canine cancer as a model for human cancer has been widely accepted as a better option than the more commonly used murine models. The dog anatomy is closer in scale to human anatomy and cancer in both species have similar characteristics. Using dogs during radiopharmaceutical pre-clinical studies can assist researchers in obtaining results that can more easily be extrapolated to humans and therefore draw more accurate conclusions regarding optimal selection of the radionuclide and delivery molecule. However the results obtained from dog studies can only be as accurate as the tools used to collect and analyze the data. Researchers are currently forced to use stylized human dosimetry programs (MIRDOSE). The stylized human phantoms of this code can only serve as rough approximations to the real anatomy and tissue dosimetry within the canine model of the disease and its experimental treatment. Upon the completion of this project, a set of three computerized anatomically realistic canine models with detailed bone microstructure and specific self-organ and cross-organ dose values for photons and beta particles will be available to researchers and veterinary doctors working on the improvement of radiation treatments for primary cancers such as osteosarcoma and more widespread conditions such as osteoblastic mestastasis stemming from breast and prostate cancers. The values obtained from the dose calculations performed on these models will be compiled in a user-friendly program. This program will also contain a database of canine bone tumor distributions characterizing their size, location and composition within a previously imaged series of canine subjects. The doses calculated by this program will be checked by comparing them with a more detailed analyses of tumor cell dose using histological sections and autoradiographic analysis of radiopharmaceutical distribution from excised tissues in dogs undergoing pre-clinical studies for new radiopharmaceutical osteosarcoma agents. Relevance: This research provides the professionals investigating new radiation treatments for bone cancer with the necessary tools to accurately calculate the organ and tumor doses in the canine model for osteosarcoma treated with radionuclide therapy. This is relevant during pre-clinical studies when the effectiveness of a drug is being determined based on the results observed during animal treatmetns. The more accurate the calculations are at that time, the more the researcher can learn about the radiopharmaceutical being evaluated.
|Padilla, Laura; Lee, Choonsik; Milner, Rowan et al. (2008) Canine anatomic phantom for preclinical dosimetry in internal emitter therapy. J Nucl Med 49:446-52|