Project Summary The EXPLORER system, built via funding from an NIH transformative R01 award, is a unique PET/CT scanner that offers: (1) an axial field of view that covers the whole adult human body in one shot; (ii) significant radiation dose reduction compared to current PET/CT protocols; (3) scans of the entire body in under 1 min; and (4) ability to visualize small structure and joints that is significantly better than current PET/CT systems. We hypothesize that EXPLORER will offer an exceptional insight into systemic Rheumatoid Arthritis (RA) pathology and provide quantitative, in vivo measures (biomarkers) for enabling a comprehensive assessment of RA disease activity and treatment response. In our first specific aim, we will establish the association between EXPLORER measures with standardized RA outcome measures. In our second specific aim, we will evaluate the capabilities of EXPLORER measures to track changes in these outcome measures in response to RA treatment. Our study will involve two groups of participants with RA. Participants in the first group will have had an inadequate response to RA non- biologic therapy and will be candidates for starting standard-of-care RA biologic therapy in addition to non- biologic therapy. These participants will be scanned on the EXPLORER system at two time points; before starting biologic therapy and 3 months after starting biologic therapy. Participants in the second group will have stable disease and will have chosen to continue to manage their RA based on the same standard-of-care non-biologic therapy. These participants will be scanned at two time points, 3 months apart. A total of 60 participants (30 per group) will be enrolled in the study. This work is innovative because the characteristics of the newly-developed EXPLORER system in terms of its field-of-view, sensitivity and spatial resolution would enable new findings relevant to both clinical and basic science research in RA. This work is significant because systemic assessment and quantification of RA disease activity based on total-body and low-dose PET/CT imaging capabilities of EXPLORER could enable improved risk stratification and precise monitoring of the effects of RA treatments on joints, and other crucial organs across the body, with scan times of just a few minutes. The ultimate beneficiaries will be RA patients as their therapeutic options will widen and treatments will be more personalized. This observational study is well-suited for the PAR- 18-597 because it focuses on associating objective imaging biomarkers with established outcome measures of RA and addresses significant obstacles in the rheumatology field regarding the applicability of an advanced imaging technique (PET/CT) in future clinical studies and clinical practice.