F-18-FEDAC as a Targeting Agent for Activated Macrophages in DBA/1 Mice with Collagen-Induced Arthritis: Comparison with F-18-FDG
- 주제(키워드) F-18-FEDAC , TSPO , activated macrophage , rheumatoid arthritis , F-18-FDG
- 주제(기타) Radiology, Nuclear Medicine & Medical Imaging
- 설명문(일반) [Chung, Seock-Jin; Yoon, Hai-Jeon; Youn, Hyewon; Kim, Mi Jeong; Lee, Yun-Sang; Jeong, Jae Min; Chung, June-Key; Kang, Keon Wook; Cheon, Gi Jeong] Seoul Natl Univ, Dept Nucl Med, Coll Med, Seoul, South Korea; [Chung, Seock-Jin; Chung, June-Key; Kang, Keon Wook; Cheon, Gi Jeong] Seoul Natl Univ, Tumor Biol Program, Coll Med, Seoul, South Korea; [Chung, Seock-Jin; Youn, Hyewon; Kim, Mi Jeong; Chung, June-Key; Kang, Keon Wook; Cheon, Gi Jeong] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea; [Yoon, Hai-Jeon] Ewha Womans Univ, Dept Nucl Med, Coll Med, Seoul, South Korea; [Youn, Hyewon; Chung, June-Key] Seoul Natl Univ, Tumor Microenvironm Global Core Res Ctr, Coll Med, Seoul, South Korea; [Youn, Hyewon; Kang, Keon Wook] Seoul Natl Univ Hosp, Canc Imaging Ctr, Seoul, South Korea; [Lee, Yun-Sang; Jeong, Jae Min; Chung, June-Key; Kang, Keon Wook; Cheon, Gi Jeong] Seoul Natl Univ, Inst Radiat Med, Med Res Ctr, Coll Med, Seoul, South Korea; [Jeong, Jae Min; Chung, June-Key; Kang, Keon Wook] Seoul Natl Univ, Coll Med, Biomed Sci, Seoul, South Korea; [Xie, Lin; Zhang, Ming-Rong] Natl Inst Quantum & Radiol Sci & Technol, Natl Inst Radiol Sci, Dept Radiopharmaceut Dev, Chiba, Japan
- 등재 SCIE, SCOPUS
- 발행기관 SOC NUCLEAR MEDICINE INC
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000151846
- 본문언어 영어
- Published As http://dx.doi.org/10.2967/jnumed.117.200667
초록/요약
Activated macrophages have been known to play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). F-18-FEDAC (N-benzyl-N-methyl- 2-[7,8-dihydro-7-(2-F-18-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 F-18-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 and Western blotting. The cellular uptake and specific binding of F-18-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. F-18-FEDAC and F-18-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 F-18-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. F-18-FEDAC uptake by arthritic joints increased early on (day 23), whereas F-18-FDG uptake did not. However, F-18-FDG uptake by arthritic joints markedly increased at later stages (day 37) to a higher level than F-18-FEDAC uptake. The F-18-FEDAC uptake correlated weakly with summed severity score (P = 0.019, r = 0.313), whereas the F-18-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: F-18-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 F-18-FEDAC imaging in the early phase of RA.
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