Project Summary This application requests funds for a stand-alone precision x-ray irradiator and imaging instrument with integrated cone beam CT (CBCT): the Xstrahl Small Animal Radiation Research Platform-200 (SARRP- 200). This instrument is requested by the faculty at The Wistar Institute in Philadelphia. The Wistar Institute is the nation’s oldest independent biomedical research institute, with an energized and highly collaborative faculty who perform cutting-edge research on cancer biology, immunology and vaccines. The Institute boasts a long history of research success in monoclonal antibody therapy and cancer biology (Stelara®) and vaccines (RotaTeq©), including the second COVID-19 vaccine to move into clinical testing in the United States. The instrument selected, the SARRP-200, introduces critical new capabilities for Wistar Investigators, who are currently unable to perform image-guided radiotherapy in small animals (mice), or to use whole-body radiation of mice for myelo-ablation using our current system. The latter technique is urgently needed for our ability to create and characterize humanized mice (mice with human immune systems). Our studies on humanized mice is a pioneering effort shared by several Investigators at the Institute, and for this and other projects it is expected that the SARRP-200 will be a critical synergy platform for Wistar research efforts. Because of IACUC restrictions regarding the transport of immuno- compromised mice, Wistar faculty are unable to use either of the two SARRPs located at the nearby University of Pennsylvania. However, we have taken advantage of the expertise of our nearby colleagues, and they are listed on our advisory board and program management team. Installation and immediate usage of the SARRP-200 will be facilitated by our already-trained personnel, our Internal Advisory Committee, and by our experienced Program Management team, which includes radiation oncology and medical physics personnel from the University of Pennsylvania. Our planned purchase of a SARRP-200 will replace a thirty year old cesium irradiator with a fragile motorized platform that is subject to frequent disrepair. The requested instrument will be placed within the Cell and Animal Irradiation Core, in designated space on the ground floor of the East Building at the Wistar Institute in Philadelphia PA, with direct access to a designated procedure room and the Laboratory Animal Facility. The planned purchase of the SARRP-200 is expected to offer significant new capabilities to Wistar researchers, and to energize the research of an already highly collaborative faculty.