Project Summary The objective of this proposal is to validate and disseminate realistic anthropomorphic phantoms to strengthen quantitative imaging for radiopharmaceutical therapies (RPTs). RPTs have shown promise in treating various cancers, but the need to accurately measure the absorbed dose in radiosensitive organs remains important. Imaging provides a mechanism to perform such quantification, and given the strong interest, multiple imaging technologies are being developed for theranostics purposes. However, a key challenge is the validation of these imaging technologies. Physical phantom-based studies provide a reliable means for conducting such evaluations. However, current phantoms lack realism, patient anatomy representation, variability in patient sizes, and sub-system resolution assessment. To overcome these limitations, as part of our parent R01, we are developing phantoms that use resin-based three-dimensional printing to create anatomically accurate models based on patient scans. This approach improves the reliability and realism of validation methods for advanced imaging techniques in RPT, benefiting patient care. Given the strong interest in RPTs across industry, academia, and clinics, multiple groups would benefit from availability of these phantoms. Thus, in this proposal, our goal is to validate these phantoms in multi-scanner and multi-center settings, and simultaneously develop robust protocols for the use of these phantoms, for wider dissemination of this technology. This proposal is thus strongly aligned with the goals of NOT-EB-24-009. We propose to validate our phantoms across multiple scanners at Washington University, as well as multiple centers including Memorial Sloan Kettering Cancer Center, Upstate Medical Center and M D Anderson Cancer Center and incorporate the feedback received to refine both the phantoms and our protocols. The resulting library of phantoms and protocols will then be deposited to the NIST/NIBIB Imaging Phantom Lending Library for wider use by the community. In addition to providing a mechanism for rigorous validation of imaging methods for theranostics with conventional reconstruction-based approaches, these phantoms facilitate the quantitative assessment of imaging systems and algorithms at sub- resolution levels, including the innovative projection domain quantification tools we have implemented via our parent R01, driving advancements in imaging science. Overall, this project has the potential to impact the fields of quantitative imaging and theranostics.