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18 F-FEDAC as a targeting agent for activated macrophages in DBA/1 mice with collagen-induced arthritis: Comparison with 18F-FDG
- 18 F-FEDAC as a targeting agent for activated macrophages in DBA/1 mice with collagen-induced arthritis: Comparison with 18F-FDG
- Chung S.-J.; Yoon H.-J.; Youn H.; Kim M.J.; Lee Y.-S.; Jeong J.M.; Chung J.-K.; Kang K.W.; Xie L.; Zhang M.-R.; Cheon G.J.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Journal of Nuclear Medicine
- Journal of Nuclear Medicine vol. 59, no. 5, pp. 839 - 845
- Society of Nuclear Medicine Inc.
- SCI; SCIE; SCOPUS
- Document Type
- Activated macrophages have been known to play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). 18F-FEDAC (N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-18F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide) is a radiolabeled ligand for the 18-kDa translocator protein (TSPO), which is abundant in activated macrophages. We evaluated the feasibility of using 18F-FEDAC in a murine RA model. Methods: RAW 264.7 mouse macrophages were activated by lipo-polysaccharide. TSPO expression levels in activated and inactivated macrophages were measured by quantitative polymerase chain reaction and Western blotting. The cellular uptake and specific binding of 18F-FEDAC were measured using a g-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 PET images were acquired on days 23 and 37 after the first immunization. Histologic examinations were performed to evaluate macrophages and TSPO expression. Results: We found increased TSPO messenger RNA and protein expression in activated macrophages. Uptake of 18F-FEDAC in activated macrophages was higher than that in nonactivated 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 correlated weakly with summed severity score (P = 0.019, r = 0.313), whereas the 18F-FDG uptake correlated strongly with summed severity score (P, 0.001, r = 0.897). Histologic sections of arthritic joints demonstrated an influx of macrophages compared with 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 the early phase of RA. COPYRIGHT © 2018 by the Society of Nuclear Medicine and Molecular Imaging.
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