PROJECT SUMMARY/ABSTRACT The objective of this proposal is to purchase a state-of-the-art microPET/CT small animal imaging scanner for the University of Wisconsin Small Animal Imaging and Radiotherapy Facility (SAIRF), which will function as a long-term shared resource for NIH-funded investigators at the UW School of Medicine and Public Health (UW SMPH). Specific aims include: Aim 1: To improve the productivity of small animal imaging research at the UW SMPH by making a state-of-the-art microPET/CT scanner accessible to federally-funded investigators, Aim 2: To enhance the ability of these investigators to perform high resolution PET and CT scanning to determine cancer treatment efficacy, biological basis of disease and using-imaging based dosimetry to provide more accurate radiotherapy dosing, and Aim 3: To foster the development of new small animal imaging resources that efficiently use the personnel and shared facility resources at the UW SMPH and UWCCC. The SAIRF provides support to faculty and trainees working on small animal imaging research projects. The laboratory offers high- quality multimodality image acquisition and analyses and consultative services on a fee-for-service basis available to the campus community and beyond. Our Siemens Inveon microPET/CT is at the end of its life and will not be supported past 2024. With this S10 grant application, we seek to replace the Inveon with a high resolution, sensitivity, and uniformity system with a compact footprint that will yield accurate quantitative data and allow seamless continuation of research for our cancer center members and University researchers. An acquisition of the Molecubes β-CUBE/X-CUBE small animal scanner meets all of these needs. This will facilitate and enhance the scientific quality and productivity of numerous NIH-funded research projects. The research programs that will use the new shared instrument seek to better understand cancer biology, the effects of external beam radiation and targeted radionuclide therapy (TRT) on tumor microenvironment, to combine radiation, including TRT, with immunotherapies with the intent of affording durable curative cancer responses accompanied with immune memory induction. The Major Users group consists of RO1, PO1, UO1, and DOD-funded investigators, while the Minor Users group also includes U54, P01, RO1 and DOD-funded investigators who request this instrument to achieve their specific aims. Exceptional departmental and institutional support (providing 41% of the purchase price) and outstanding technical expertise assure that the requested equipment will be operable immediately and highly productive at UW for many years to come.