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PET and fluorescence imaging of translocator protein 18 kDa expression in rodent models of myocarditis and glioblastoma : 심근염 및 교모세포종 모델에서 PET과 형광영상을 이용한 전이체 단백질 18 kDa 발현의 평가
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- Authors
- Advisor
- 김상은
- Major
- 융합과학기술대학원 융합과학부
- Issue Date
- 2018-02
- Publisher
- 서울대학교 대학원
- Keywords
- translocator protein ; myocarditis ; glioblastoma multiforme ; positron emission tomography ; fluorescence imaging
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 융합과학기술대학원 융합과학부, 2018. 2. 김상은.
- Abstract
- Translocator protein 18 kDa (TSPO), which is located mainly in the outer membrane of the mitochondria, is considered as a potential biomarker of inflammation or specific cancers because of its overexpression in such lesions. This protein is closely associated with inflammatory responses in various diseases, including myocarditis or glioblastoma multiforme (GBM). Here, we evaluated TSPO overexpression using TSPO radiotracers, [18F]fluoromethyl-PBR28 [18F]1) and [18F]CB251 ([18F]2), and TSPO-targeted iron oxide nanoparticles in different rodent disease models to precisely diagnose each lesion. Both the radiotracers, [18F]1 and [18F]2, were successfully prepared in an automated module and compared between in an experimental autoimmune myocarditis (EAM) model and a healthy control by positron emission tomography (PET) imaging to determine which is more suitable for in vivo TSPO assessment. [18F]2 showed a more specific TSPO uptake in the heart of EAM rats (1.32-fold higher heart-to-lung uptake ratio) than in that of healthy rats, whereas [18F]1 showed similar heart uptake patterns between the two groups. Histopathological analysis of the heart tissues from each group demonstrated abnormal TSPO expression in inflammatory myocardial tissues compared with control tissues. Nanoparticles were prepared with TSPO ligands (CB235) and Cy5.5 dyes which were introduced on the surface of the nanoparticles, and were evaluated in a subcutaneously implanted glioblastoma xenograft mouse model by fluorescence imaging. The fluorescence signal from tumors was strongest at 8 h, and 71.3% of the uptake at 8 h was maintained after 24 h despite rapid clearance from other organs (highest tumor-to-background ratio at 24 h). These results demonstrated that the imidazole[1,2-a]pyridine-based radiotracer [18F]2 is a sensitive tool for the noninvasive diagnosis of myocarditis
thus, it may be applied to clinical settings for the early diagnosis of human myocarditis. Moreover, the tumors were visualized using TSPO-targeted fluorescent nanoparticles. The findings suggest that the specificity and selectivity of TSPO-targeted nanoparticles may facilitate tumor diagnosis, serving as a guide for surgical treatment.
- Language
- English
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