Abstract Purpose While the aetiology of rheumatoid arthritis (RA) remains unclear, many of the inflammatory components are well characterised. For diagnosis and therapy evaluation, in vivo insight into these processes would be valuable. Various imaging probes have shown value including dynamic contrast-enhanced (DCE) MRI and PET/CT using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) or tracers targeting the translocator protein (TSPO). To evaluate ¹⁸F-GE-180, a novel TSPO PET tracer, for detecting and quantifying disease activity in RA, we compared ¹⁸F-GE-180 uptake with that of ¹⁸F-FDG and DCE-MRI measures of inflammation. Methods Eight RA patients with moderate-to-high, stable disease activity and active disease in at least one wrist were included in this study (NCT02350426). Participants underwent PET/CT examinations with ¹⁸F-GE-180 and ¹⁸F-FDG on separate visits, covering the shoulders and from the pelvis to the feet, including hands and wrists. DCE-MRI was performed on one affected hand. Uptake was compared visually between tracers as judged by an experienced radiologist and quantitatively using the maximum standardised uptake value (SUV_max). Uptake for both tracers was correlated with DCE-MRI parameters of inflammation, including the volume transfer coefficient K^trans using Pearson correlation (r). Results PET/CT imaging with ¹⁸F-GE-180 in RA patients showed marked extra-synovial uptake around the affected joints. Overall sensitivity for detecting clinically affected joints was low (14%). ¹⁸F-GE-180 uptake did not or only weakly correlate with DCE-MRI parameters in the wrist (r = 0.09–0.31). ¹⁸F-FDG showed higher sensitivity for detecting symptomatic joints (34%), as well as strong positive correlation with DCE-MRI parameters (SUV_max vs. K^trans: r = 0.92 for wrist; r = 0.68 for metacarpophalangeal joints). Conclusions The correlations between DCE-MRI parameters and ¹⁸F-FDG uptake support use of this PET tracer for quantification of inflammatory burden in RA. The TSPO tracer ¹⁸F-GE-180, however, has shown limited use for the investigation of RA due to its poor sensitivity and ability to quantify disease activity in RA.