PROJECT SUMMARY Weill Medical College of Cornell University (Weill Cornell Medicine, WCM) and Memorial Sloan- Kettering Cancer Center (MSK) request High-End Instrumentation Grant Program support to purchase major upgrades and a refurbishment of our 20-year-old jointly owned and operated 19 MeV cyclotron. The cyclotron is a major component of WCM and MSK strategic investments in crucial imaging infrastructure used to advance basic, translational and clinical research, and is a vital tool for our large and growing pool of investigators who utilize positron emission tomography (PET) in their projects. At this point, all major components of the cyclotron are at or beyond their end of life and are facing end-of-service status due to lack of available parts. In some cases, the components are degraded to the point that catastrophic failure requiring significant downtime and cost is possible in the near term. In addition, in order to support our large and growing pool of NIH funded investigators, we require features that are not available in our current cyclotron configuration. WCM and MSK are world leaders in biomedical research, and our cyclotron partnership over the past 20 years has leveraged the technical expertise of both institutions to ensure efficient radioisotope while realizing the significant benefits of cost sharing. The proposed upgrades and refurbishment will provide us with new state-of-the-art cyclotron technology, including complete replacement of the ion source, radiofrequency, computer control, and target assembly subsystems, that will facilitate innovative research projects using PET over the next two decades. Successful completion of this project will contribute significantly to our goal of understanding and treating a wide range of diseases, including neurodegeneration, cancers, psychiatric disorders, genetic disorders, inflammatory diseases, and vascular diseases. The cyclotron is located at the Citigroup Biomedical Imaging Center (CBIC), which is a dedicated, comprehensive, imaging research and development facility located on the campus of the Medical College. The CBIC operates as an imaging research Core facility that serves over 100 investigators from 12 institutions in the greater New York area. The campus is immediately adjacent to the campus of Memorial Sloan-Kettering Cancer Center. MSK also operates a large imaging Core facility dedicated to oncologic applications. Both institutions have burgeoning imaging research programs with high demand for cyclotron-produced radiotracers used in positron emission tomography (PET). The proposed upgrades and refurbishment are critical to our mission of providing high-level, uninterrupted research support for investigators funded by the National Institutes of Health and other sponsors on both campuses.