PROJECT SUMMARY – RADIONUCLIDE PRODUCTION AND RADIOCHEMISTRY CORE 1 The Department of Medical Physics controls three different particle accelerator laboratories equipped with a variety of irradiation, radiochemistry, and radioanalytical equipment that will be used to investigate the symbiotic effects of targeted radiotherapy (TRT) and the immunological methodologies of Projects 1-4. The Cyclotron Laboratories’ principle site in the Wisconsin Institutes of Medical Research (WIMR) hosts a General Electric PETtrace 16-MeV proton / 8-MeV deuteron cyclotron surrounded by 4000 square feet of laboratory space used for radiochemical and accelerator research, as well as the routine production and international distribution of numerous radionuclides to a global customer base. The cyclotron laboratory infrastructure accommodates tens of Ci-quantities of radioactivity in automated processes using homemade and commercial equipment and is internationally established as a leader in solid, liquid, and gas phase accelerator targetry, primarily for positron- emission tomography (PET) radionuclide production. Spectroscopic/spectrometric analysis is accomplished with multiple high purity germanium detectors and a variety of configurable electronic equipment. Most recently, our research into alloy targetry for small, medical accelerators has enabled us to increase production of several radionuclides of interest to previously unprecedented levels. This laboratory currently produces 89Zr, 76/77Br, 86Y, 52gMn and more than two dozen other radionuclides on a weekly basis for local use and shipment to over 60 collaborators, colleagues, pharmaceutical companies, and globally premier research institutions in the US and abroad. The laboratory also hosts biosafety cabinets inside radiation areas for in vitro study of the unique radionuclides we produce, adjacent to the laboratory space of the Small Animal Imaging Core. Finally, the Department of Radiology recently finished construction of a GMP Radiopharmacy lab. The Radiopharmaceutical Production Facility (RPF) is situated within the WIMR complex across the hall from the cyclotron facility. It houses a new manufacturing area designed for the production of cGMP radiopharmaceuticals. This area is equipped with multiple hot cells and synthesis modules and includes multiple quality control instruments to accommodate segregation of clinical and preclinical production activities. A dispensing area designed in compliance with USP <797> has the capability to compound and distribute radiopharmaceuticals. Although clinical trials are not the aim of the PO1, we have the ability to rapidly translate the treatment paradigms discovered and developed within the PO1 to the clinical trial stage. The specific aim of the Radionuclide Production and Radiochemistry Core (RPRC) is to directly produce and supply pure imaging and therapy radionuclides and radiochemically synthesize all imaging/therapy/immunomodulatory doses of radiopharmaceuticals ...