Imaging disease activity of rheumatoid arthritis by macrophage targeting using second generation translocator protein positron emission tomography tracers

BACKGROUND: Positron emission tomography (PET) imaging of macrophages using the translocator protein (TSPO) tracer (R)-[(11)C]PK11195 has shown the promise to image rheumatoid arthritis (RA). To further improve TSPO PET for RA imaging, second generation TSPO tracers [(11)C]DPA-713 and [(18)F]DPA-714 have recently been evaluated pre-clinically showing better imaging characteristics. OBJECTIVE: A clinical proof of concept study to evaluate [(11)C]DPA-713 and [(18)F]DPA-714 to visualize arthritis in RA patients. METHODS: RA patients (n = 13) with at least two active hand joints were included. PET/CT scans of the hands were obtained after injection of [(18)F]DPA-714, [(11)C]DPA-713 and/or (R)-[(11)C]PK11195 (max. 2 tracers pp). Standardized uptake values (SUVs) and target-to-background (T/B) ratios were determined. Imaging data of the 3 different tracers were compared by pooled post-hoc testing, and by a head to head comparison. RESULTS: Clinically active arthritis was present in 110 hand joints (2–17 pp). Arthritic joints were visualized with both [(11)C]DPA-713 and [(18)F]DPA-714. Visual tracer uptake corresponded with clinical signs of arthritis in 80% of the joints. Mean absolute uptake in PET-positive joints was significantly higher for [(11)C]DPA-713 than for [(18)F]DPA-714, the latter being not significantly different from (R)-[(11)C]PK11195 uptake. Background uptake was lower for both DPA tracers compared with that of (R)-[(11)C]PK11195. Higher absolute uptake and lower background resulted in two-fold higher T/B ratios for [(11)C]DPA-713. CONCLUSIONS: [(11)C]DPA-713 and [(18)F]DPA-714 visualize arthritic joints in active RA patients and most optimal arthritis imaging results were obtained for [(11)C]DPA-713. Second generation TSPO macrophage PET provides new opportunities for both early diagnosis and therapy monitoring of RA.