Journal Article [18F]FEDAC as a targeting agent for activated macrophages in DBA/1 mice with collagen-induced arthritis: Comparison with [18F]FDG

Seock-Jin, Chung  ,  Hai-JeonYoon  ,  Jeong Cheon, Gi  ,  Youn, Hyewon  ,  Jeong Kim, Mi  ,  Xie, Lin  ,  Yun-Sang, Lee  ,  Min Jeong, Jae  ,  June-Key, Chung  ,  Wook Kang, Keon  ,  Ming-Rong, Zhang

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). Immunohistochemical staining of the arthritic joint demonstrated an influx of macrophages compared to that in normal joints.Conclusions [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.

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