서울대 / 송유성, 이상희, 이병철*, 김상은*
Abstract
We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option.
Affiliations
Yoo Sung Song 1 , Sang Hee Lee 1 2 , Jae Ho Jung 1 , In Ho Song 1 , Hyun Soo Park 1 , Byung Seok Moon 3 , Sang Eun Kim 1 4 5 , Byung Chul Lee 1 5
1 Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
2 Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.
3 Department of Nuclear Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul 07804, Korea.
4 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.
5 Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 16229, Korea.
편집위원
이 논문은 동물모델을 이용한 3-[18F]F-CP118,954를 이용한 AChE (acetylcholinesterase)표적 PET 영상과 [18F]fluoromethyl-PBR28-d2를 이용한 18 kDa TSPO (translocator protein)표적 PET 영상에 대한 연구이다. 결과적으로, MCAO(middle cerebral artery occlusion) Spague-Dawley rat 동물모델을 이용하여 뇌졸중 후 염증성 뇌 반응 과정을 AChE / TSPO PET 영상을 통해 확인할 수 있었다.
2021-06-30 16:13:41