7. Project Summary/Abstract. This application requests funds for a state-of-the-art shared resource, the X-Rad Small-Animal Radiation Therapy (SmART)+ Biological Irradiator (Precision X-Ray, North Branford, CT), to replace our existing X- Rad 225Cx Biological Irradiator (also manufactured by Precision X-Ray). Pursuant to Precision X-Ray’s “end- of-life” letter, “…the EOL (End Of Life) is the date - December 31st, 2020 - after which we will no longer be able to service and/or cover the unit under a new support agreement.” (Precision X-Ray subsequently agreed to provide service support for our X-Rad 225Cx Biological Irradiator exclusive of the X-ray tube and generator through December 31st, 2021.) Radiation therapy (RT) remains, of course, one of the most widely used and effective cancer treatment modalities, and Memorial Sloan Kettering Cancer Center (MSK) has long been recognized as a worldwide leader in research, development, and patient care in RT. Since its installation in 2014, our heavily used X-Rad 225Cx Biological Irradiator has contributed enormously to this legacy, providing invaluable technical capabilities for NIH-funded basic and translational investigations on the response of normal tissues and tumors in experimental rodent models to therapeutic external-beam irradiation. Clinical- grade external-beam radiation therapy is now an essential component of the pre-clinical oncology research program at MSK. The instrument requested, the state-of-the-art X-Rad SmART+, is an image-guided, isocentric (360 rotation, with arc therapy capability), self-shielded research irradiator combining a high- resolution (100 m) cone-beam CT imaging system and a high-dose rate (up to approximately 5 Gy/min) therapeutic X-ray source into a single integrated, computer-controlled platform. It includes a wide variety of fixed-field collimators – circular (0.5 to 25 mm in diameter), square (3 x 3 to 40 x 40 mm), and rectangular (8 x 12 to 30 x 40 mm) – plus an adaptable field-shaping collimator. The X-Rad SmART+ also includes SmART - ATP (Advanced Treatment Planning), a clinical-grade Monte Carlo modeling-based treatment planning system. Similar to its predecessor, the X-Rad 225Cx, the X-Rad SmART+ Biological Irradiator is a complex instrument requiring timely manufacturer-provided service and applications support and periodic software updates to ensure the reliable performance which cutting-edge, often time-sensitive experimental work demands. Without such support, important funded experiments would be very seriously compromised or abandoned altogether. The X-Rad SmART+ Biological Irradiator is thus essential for the ongoing work of numerous highly productive, NIH-funded projects in MSK’s pre-clinical oncology research program.