Abstract
Activated macrophages have been known to play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). 18F-FEDAC is a radiolabeled ligand for the translocator protein (TSPO), which is abundant in activated macrophages. We evaluated the feasibility of 18F-FEDAC in a murine RA model. Methods: RAW 264.7 mouse macrophages were activated by lipopolysaccharide. TSPO expression levels in activated and inactivated macrophages were measured by quantitative polymerase chain reaction (qPCR) and western blotting. The cellular uptake and specific binding of 18F-FEDAC were measured using a gamma counter. For the in vivo study, collagen-induced arthritis (CIA) was developed in DBA/1 mice and the clinical score for arthritis was measured regularly. 18F-FEDAC and 18F-FDG positron emission tomography (PET) images were acquired on days 23 and 37 after first immunization. Histological examinations were performed to evaluate macrophages and TSPO expression. Results: We found increased TSPO mRNA and protein expression in activated macrophages. Uptake of 18F-FEDAC in activated macrophages was higher than that in non-activated cells, and was successfully blocked by the competitor PK11195. In CIA mice, joint swelling was apparent on day 26 after the first immunization and the condition worsened by day 37. 18F-FEDAC uptake by arthritic joints increased early on (day 23), whereas 18F-FDG uptake did not. However, 18F-FDG uptake by arthritic joints markedly increased at later stages (day 37) to a higher level than 18F-FEDAC uptake. The 18F-FEDAC uptake was weakly correlated with summed clinical severity score (P = 0.019, r=0.313), whereas the 18F-FDG uptake was strongly correlated with summed severity score (p<0.001, r=0.897). Histologic sections of arthritic joints demonstrated an influx of macrophages compared to that in normal joints. Conclusion: 18F-FEDAC enabled the visualization of active inflammation sites in arthritic joints in a CIA model by targeting TSPO expression in activated macrophages. The results suggest the potential usefulness of 18F-FEDAC imaging in early phase of RA.
- Animal Imaging
- Joint/Muscle
- Molecular Imaging
- PET/CT
- 18F-FDG
- 18F-FEDAC
- Activated macrophage
- Rheumatoid arthritis
- TSPO
- Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.