UWCCC Imaging and Radiation Sciences Program Summary Co-Leaders: Robert Jeraj and Randy Kimple PROJECT SUMMARY/ABSTRACT The Imaging and Radiation Sciences (IR) Program’s mission is to integrate physical and biological sciences with clinical research and clinical practice to improve cancer diagnosis, therapy, and the lives of patients with cancer. The exceptional environment within the UWCCC and the IR program provides an opportunity to advance imaging, radiopharmaceutical, molecularly-targeted radiobiology, and radiation therapy across the translational science spectrum from basic mechanisms through clinical trials. These goals are achieved through three connected aims. Aim 1: To develop and translate innovative imaging agents and technologies to improve cancer detection and treatment response assessments. IR program members focus on development and translation of novel molecular imaging agents, such as radiolabeled nanomaterials, refinement of quantitative imaging methods, and development of innovative image-analysis techniques, including advanced artificial intelligence methods. Aim 2: To develop and translate radiopharmaceuticals for more effective personalization of systemic radiation therapies. IR program members focus on development of novel positron and low energy electron-emitting radionuclides and radiopharmaceutical delivery vehicles, combinations of radiopharmaceuticals with immunotherapy, and the development and clinical translation of theranostic agents. Aim 3: To develop and translate advances in the management of localized radiation therapies to improve therapeutic response and minimize side effects. IR program members focus on localized tumor ablation, combining localized therapies with systemic therapies to target oligo-resistance, understanding molecular mechanisms underlying therapeutic resistance, and reducing treatment toxicities through novel cellular therapies and by employing unique combinations of imaging and treatment planning to improve the quality of therapeutic interventions. Notable achievements since the last CCSG renewal include doubling clinical trial accrual compared to the time of the last CCSG renewal, with many of trials being translated nationwide reflected by almost 40% of IR members holding leadership roles in cooperative groups. IR members have received multiple large multi-investigator studies including an Immuno/Radiopharmaceutical P01, a UG3/UH3 supporting a first- in-human study of cell therapy for treatment of radiation-induced xerostomia and have been in key leadership roles in the Head and Neck cancer SPORE renewal (favorably reviewed) and breast and prostate cancer SPORE grant submissions. These productive efforts are well supported: 41 members from 6 departments have a total of $9.8M in annual direct costs ($3.4M from NCI, double compared to the prior cycle). These research efforts have led to 897 peer-reviewed publications in the last five-year funding period, including an exceptional 19% in jou...