18 F-FEDAC as a Targeting Agent for Activated Macrophages in DBA/1 Mice with Collagen-Induced Arthritis: Comparison with 18 F-FDG.

Autor:	Chung SJ; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.; Tumor Biology Program, Seoul National University College of Medicine, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea., Yoon HJ; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.; Department of Nuclear Medicine, College of Medicine, Ewha Womans University, Seoul, Korea., Youn H; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Tumor Microenvironment Global Core Research Center, Seoul National University College of Medicine, Seoul, Korea.; Cancer Imaging Center, Seoul National University Hospital, Seoul, Korea., Kim MJ; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea., Lee YS; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.; Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea., Jeong JM; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.; Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.; Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; and., Chung JK; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.; Tumor Biology Program, Seoul National University College of Medicine, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Tumor Microenvironment Global Core Research Center, Seoul National University College of Medicine, Seoul, Korea.; Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.; Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; and., Kang KW; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.; Tumor Biology Program, Seoul National University College of Medicine, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Cancer Imaging Center, Seoul National University Hospital, Seoul, Korea.; Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.; Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; and., Xie L; Department of Radiopharmaceutical Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Zhang MR; Department of Radiopharmaceutical Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Cheon GJ; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea larrycheon@gmail.com.; Tumor Biology Program, Seoul National University College of Medicine, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2018 May; Vol. 59 (5), pp. 839-845. Date of Electronic Publication: 2018 Jan 11.
DOI:	10.2967/jnumed.117.200667
Abstrakt:	Activated macrophages have been known to play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). 18 F-FEDAC ( N -benzyl- N -methyl-2-[7,8-dihydro-7-(2- 18 F-fluoroethyl)-8-oxo-2-phenyl-9 H -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 18 F-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 18 F-FEDAC were measured using a γ-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. 18 F-FEDAC and 18 F-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 18 F-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. 18 F-FEDAC uptake by arthritic joints increased early on (day 23), whereas 18 F-FDG uptake did not. However, 18 F-FDG uptake by arthritic joints markedly increased at later stages (day 37) to a higher level than 18 F-FEDAC uptake. The 18 F-FEDAC uptake correlated weakly with summed severity score ( P = 0.019, r = 0.313), whereas the 18 F-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: 18 F-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 18 F-FEDAC imaging in the early phase of RA. (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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