PROJECT SUMMARY / ABSTRACT Operating within the University of Wisconsin Carbone Cancer Center (UWCCC), the Small Animal Imaging & Radiotherapy Facility (SAIRF) provides innovative, state-of-the-art, affordable, noninvasive, high-resolution, in- vivo and ex-vivo imaging and radiotherapy support to UWCCC members who utilize small animal models in their research. SAIRF experts provide guidance to investigators ensuring the experimental design is best suited to address their cancer questions. Incorporating positron emission/computed tomography (PET/CT), single photon emission computed tomography (SPECT/CT), magnetic resonance imaging (MRI), ultrasound/photoacoustics (US/PA), digital planar X-ray, and/or optical bioluminescence/fluorescence/near-infrared (NIR) imaging modalities, SAIRF affords access to all major small animal imaging modalities. Additionally, SAIRF provides radiotherapy support, offering x-ray irradiators for cell, whole body, and CT-guided radiation therapy, and dedicated equipment to assay radioactive tissues/blood for biodistribution, pharmacology, and toxicology applications. Moreover, UWCCC members can select their desired level of service ranging from radiotherapy delivery/image acquisition and reconstruction, to interpretation, analysis, and/or figure preparation. In most cases, proprietary agents are developed and produced in-house with collaborators and when necessary, commercial agents (Tc-99m MDP, Lu-177 Lutathera, Ra-223 dichloride, etc) are acquired for imaging and radionuclide therapy studies. SAIRF holds umbrella animal use, biosafety, and radiation safety protocols, thus assuring appropriate regulatory control of imaging and radiotherapy studies while minimizing the regulatory burden on individual investigators. SAIRF supports the preclinical development of new imaging and theranostic agents intended for clinical translation. One such agent, NM404, initiated here and underwent extensive preclinical evaluation within SAIRF prior to translating to clinical trials. During the current CCSG funding cycle, SAIRF has provided critical imaging support to 79 unique UWCCC members across all six UWCCC programs. We continue to assess new imaging, radiotherapy and related technologies and, if suitable and relevant to the membership, develop a plan to bring such new technologies into SAIRF. Our specific aims are to provide: 1) UWCCC members seamless access and guidance to the most advanced small animal cancer imaging and radiotherapy technologies available, and 2) infrastructure and expertise for the preclinical discovery and development of new molecular imaging and theranostic cancer agents. Funding provided from the CCSG permits consultation, strategic planning, training, regulatory and quality oversight in support of our mission to serve the UWCCC membership at the highest level while minimizing costs. We expect that our role in development and evaluation of new imaging and therapy agents, especially those being developed by our ...