ABSTRACT This proposal requests funds to acquire a new state-of-the-art MOLECUBES small animal imaging system with Positron Emission Tomography (PET) and Computed Tomography (CT) capabilities to support pre-clinical research at the University of Texas Southwestern Medical Center (UTSW). This multi-modality system includes the highest sensitivity PET system commercially available and a high-resolution CT for routine animal imaging with low radiation exposure. This equipment is selected compared to other commercially available scanners, also because of its compact size and light weight, user-friendly interface and intuitive workflow, high- throughput imaging capability, modular design enabling future expandability, as well as compatibility with other existing devices. UTSW has a long and successful record of accomplishment in conducting ground-breaking biomedical research. Many projects significantly benefit from in vivo imaging to acquire structural and functional information. Especially with the establishment of Cyclotron and Radiochemistry Program offering onsite production of novel PET tracers, a UTSW program funded by the Cancer Prevention and Research Institute of Texas (CPRIT), desire for pre-clinical PET/CT imaging has been growing substantially because of more scanning opportunities, access to short-lived isotopes, more types of isotopes for expanded research endeavors, and reduced costs associated with isotope transport from elsewhere. Nonetheless, currently there is only one PET/CT scanner in UTSW, which employed older-generation PET/CT technologies and cannot meet the technical needs in imaging quality and scanning efficiency. More critically, this scanner is located outside the Specific-pathogen-free animal facility, substantially limiting scope of projects behind the animal barrier, e.g. those using immuno-deficient animals, and prohibiting studies requiring multiple PET/CT scans, e.g. for longitudinally monitoring disease progression. The requested PET/CT will be installed in and managed by PreClinical Radition Core Facility (PCRCF) of UTSW located behind the animal barrier, a CPRIT-funded shared resource facility for in vivo imaging and radiation technologies and services. This setting allows maximally taking advantages of existing instrument and management infrastructure of the PCRCF to provide users a one-stop solution to access all major imaging modalities (PET/CT/MR/Optical imaging) and radiation delivery techniques (image-guided small animal irradiator), as well as extensive imaging and radiation physics expertise. To demonstrate the need for the requested PET/CT, we have assembled Major and Minor user groups. Their diverse spectrum of projects, majority of which funded by the NIH, ensures adequate use of the equipment. We have formed an Advisory Board to oversee the PET/CT operation and developed a sustainable financial plan. The requested instrument will meet a significant need of our institution for state-of-the-art in vivo ...