b'Development of NovelLinking a multi-functional molecular construct to a tumor-seeking Radiometal Chelators forantibody enables cancer diagnosis and radiation treatment.Imaging and TherapeuticE nergy of radioactive decay may be deposited to the malignant cell if an unstable atom is delivered near a tumor. This well-known radiotherapeutic Nuclear Medicine concept was a backbone of this project where a multi-modal radiometal carrier was built for numerous biomedical applications. The molecular unit uses a functionalized phosphazene platform, which is decorated with structures designed to bind radiometals and attach to cancer-seeking antibodies. This approach adds versatility to diagnostics and treatment of cancer with radiation. Different radiometals can be delivered near tumor cells to offer concerted options for positron PROJECT NUMBER:emission tomography, Cherenkov-sensitized fluorescence, magnetic resonance 20A44-089 imaging, and x-ray induced Auger electron radiosensitization. TOTAL APPROVED AMOUNT:Novel molecules (chelates) were synthesized to build strong coordination $1,100,000 over 3 years environments and withstand metal binding pressures of complex in vivo conditions. Chelates coordinate a variety of medical isotopes such as radiostrontium and PRINCIPAL INVESTIGATOR:radiolanthanides, serving as armored delivery vehicles in the human body. In this Peter Zalupski work, chelates were adapted to offer compatibility with click chemistry, which CO-INVESTIGATORS: is a convenient bioconjugation tool for linking molecular units. This synthetic John Klaehn, INL strategy connected multiple chelates to a phosphazene platform. Bioconjugation, Aidan Bender, University of Utah i.e., attachment of chelate to antibody, was also enabled via click chemistry after Tara Mastren, University of Utah antibody surface functionalization.Santa Jansone-Popova, Oak Ridge National Laboratory TALENT PIPELINE:Aidan Bender, student at University of UtahHO HO OO NHO O ONHO N OHOHN SNHONN 3N N NO O N NO P N P N NN 3 O N P O N HO N SN 3 O HNO N N OHO OH N N HOHO N O S NH O N N OO N NH HO O O N HO OHO O N HOOHO HOIllustration of multi-modal radiometal carrier concept developed for simultaneous tumor imaging and therapy options. Structure shows a synthesized molecular construct where three chelate units are available for radiometal binding and three vectors are available for attachment to monoclonal antibody.19'