서울의대 / 정석진, 윤혜전, 천기정*
(그림 1)18F-FEDAC PET의 TSPO 수용체에 대한 특이적 결합을 확인하기 위해 동일한 CIA 마우스를 이용하여 차단 실험을 진행하였다. CIA 마우스에 TSPO에 대한 specific ligand인 과량의 cold-form PK11195를 전처리하였을 때 (blocking PET), 관절염 부위의 18F-FEDAC 섭취가 유의하게 감소하였다 (p<0.001)
(그림 2)18F-FEDAC PET은 관절염이 발현하기 전 시점 (유도 후 23일)에도 관절 내 섭취 증가를 보였으나, 18F-FDG PET은 같은 시점에 관절 내 섭취를 보이지 않았다. 유도 후 37일 째 충분히 관절염이 발현된 상태에서는 18F-FEDAC, 18F-FDG PET 모두 관절 내 섭취를 보이고 있다.
Abstract
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 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 18F-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. 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.
Author information
Chung SJ1,2,3, Yoon HJ1,4, Youn H1,3,5,6, Kim MJ1,3, Lee YS1,7, Jeong JM1,7,8, Chung JK1,2,3,5,7,8, Kang KW1,2,3,6,7,8, Xie L9, Zhang MR9, Cheon GJ10,2,3,7.
1
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
2
Tumor Biology Program, Seoul National University College of Medicine, Seoul, Korea.
3
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
4
Department of Nuclear Medicine, College of Medicine, Ewha Womans University, Seoul, Korea.
5
Tumor Microenvironment Global Core Research Center, Seoul National University College of Medicine, Seoul, Korea.
6
Cancer Imaging Center, Seoul National University Hospital, Seoul, Korea.
7
Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
8
Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; and.
9
Department of Radiopharmaceutical Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
10
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea larrycheon@gmail.com.
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편집위원
대식세포는 류마티스 관절염에 발병에 중요한 역할을 하므로 이에 대한 비침습적인 영상법은 해당 질환의 병리 생태를 이용한데 유용할 것임. 해당 연구는 TSPO에 대한 리간드로 18F-FEDAC 를 이용하여 활성 대식세포를 소동물에서 영상화하였음. 이러한 연구 결과는 류마티스 전문가 및 임상 핵의학자에게 유용한 정보를 제공할 것으로 생각됨. 또한 방사성의약품을 개발하는데 관심이 있는 기초 연구자에게도 흥미를 끌 수 있을 것임.
2018-06-21 11:06:39
편집위원2
종양에만 국한된 것이 아닌 양성 질환에서의 PET/CT의 유용성에 대한 연구가 인상적입니다.
2018-06-21 11:23:31