This S10 shared instrumentation grant will fund the purchase of a Cone Beam CT Guided Small Animal Radiation Research Platform (SARRP), manufactured by Gulmay Medical, Inc., Suwanee, GA. There is a critical need for this machine, which is a preclinical research tool for studies on small animals (mice and rats) that can model the exposures given to humans in therapeutic settings. Although the technology for clinical radiation therapy has advanced significantly in the past 25 years, the methods for radiation delivery in a laboratory setting have lagged behind. Modern radiotherapy uses image guidance to deliver highly conformal radiation to a target volume while sparing normal tissue structures. By contrast, methods used in animal research to irradiate spontaneous or orthotopic tumors and their metastases are guided by external features alone, and generally expose a large portion of the body to radiation. The SARRP offers a powerful new technology for preclinical studies in translational radiation biology. The SARRP is portable, with on-board cone beam CT imaging (0.25-0.5 mm voxel size) to guide radiation delivery. It can deliver highly conformal radiation to target volumes with sub-millimeter accuracy. As such, it can precisely irradiate animals with a level of precision that approaches current clinical practice. Sparing normal tissue is essential as we move towards hypofractionated treatment schedules to pilot approaches to bring to the clinic. The SARRP irradiator is based on the prototype developed by Dr. John Wong, Director of Radiation Physics, Johns Hopkins University. Dr. Wong's instrument has been in use for seven years, and there are 17 more in service in the USA and elsewhere. Dr. Wong will serve as a consultant for our group. Administration of the instrument will be by the PI, the Co-Investigator for Medical Physics and the Co-investigator for Radiation Oncology/Radiation Biology. Assisting the Administration is an Internal Advisory Committee with demonstrated expertise in radiation biology (PI), medical physics, radiation oncology, experimental oncology, nuclear medicine/ radiopharmaceutical chemistry (Director of the Small Animal Imaging Facility) and cell biology/immunology (Director of the Kimmel Cancer Center Shared Resources for Flow Cytometry &Cs-137 Irradiation). The Division of Molecular Radiation Biology is one of the more active radiation biology groups in the USA with a strong emphasis on translational research. The Medical Physics Division has expertise in conformal and stereotactic treatment planning, online image fusion and setup correction, which directly supports use of this high-end irradiator. Funds to support operation of the machine will come from the Administration of the University, the Medical College Administration, the Kimmel Cancer Center and the Department of Radiation Oncology and from user fees. We have 20 NIH-funded users and five users with non-NIH research funding. Jefferson has a long history of academic radiology, radiation oncology and radiation biology. The acquisition of this state-of-the-art machine will allow for a quantum leap forward for our translational radiation oncology research environment.