PROJECT SUMMARY: Investigators at our institution have used translational rodent models to examine the effects of radiation on tumors and normal tissues since 1955. Today our radiation research is largely focused on sensitizing tumors to radiation therapy by introducing novel small molecule, antibody, immunologic, or genetic therapies. However, standard orthovoltage delivery devices are unable to recapitulate clinical radiation protocols. They do not provide accuracy or homogeneity of dose delivery, targeting of discrete lesions or organs, sparing of normal tissues, or the dose-volume calculations essential for understanding tissue exposures. The small animal radiation research platform (SARRP)-200 PRO addresses these limitations and enables target-based treatment planning using an integrated cone beam CT scan (CBCT) and image guided micro-irradiation. The SARRP will be integrated in to the Yale Cancer Center Irradiator Core and its specialized use will also be overseen by the PI and an advisory committee. The instrument will support several ongoing NIH funded research projects in cancer biology, enhance experimental designs, and improve data analysis and interpretation. Examples of how the SARRP will augment ongoing research are readily available. The SARRP will improve target localization within the brain, a site investigated by many projects at Yale, as well as other anatomic sites. It will enable delivery of radiosurgery, required by several investigators that seek to reproduce clinical scenarios with high radiation dose per fraction regimens. It will also provide the ability to study the interactions of radiation with normal tissue and the immune system, and to evaluate therapeutic responses at local, regional, and distant sites following irradiation. The use of SARRP guided radiation delivery is also anticipated to recruit new users, provide educational experience with this technology for trainees, and significantly expand research in tumor biology and the radiation sciences.