18F-FINH-Me检测阿尔茨海默病模型鼠脑内β-淀粉样斑块沉积n

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目的:制备新型β-淀粉样蛋白(Aβ)显像剂(2-((2-6-[n 18F]氟-5-(甲氨基)吡啶-2-基)苯并噻唑-6-基)硫代)乙醇(n 18F-FINH-Me),评价其生物学分布及其与Aβ的亲和性。n 方法:使用GE FN自动化模块合成n 18F-FINH-Me,采用高效液相色谱(HPLC)对产品进行质量控制及稳定性检测。研究n 18F-FINH-Me在正常C57BL/6小鼠(n n=25)体内的生物学分布;对阿尔茨海默病(AD)模型鼠(n n=5)和与其年龄及背景匹配的正常C57BL/6小鼠(n n=5)进行microPET/CT显像。取小鼠脑组织进行Aβ免疫组织化学染色;取AD患者(女,69岁)和健康志愿者(女,66岁)死后的人脑切片进行n 18F-FINH-Me放射自显影。n 结果:18F-FINH-Me衰减校正后的产率为(53±4)%(n n>20);放射性纯度>98%(n n>20);比活度达79.90~122.00 GBq/μmol (n n=10);室温下在磷酸盐缓冲液(PBS)中温育4 h无脱氟现象,稳定性好。生物学分布表明,n 18F-FINH-Me主要经过肝肾排泄。MicroPET/CT显像示AD小鼠脑内n 18F-FINH-Me有明显放射性摄取,注射后1~2 min达到峰值,且洗脱速度快(全脑标准摄取值:注射后1 min 0.73±0.17,注射后30 min 0.31±0.06)。免疫组织化学结果显示AD模型鼠脑内有丰富的Aβ斑块沉积,而正常C57BL/6小鼠脑内无斑块沉积。放射性自显影结果表明n 18F-FINH-Me对AD患者脑内沉积的Aβ斑块高标记,而在健康志愿者的脑切片中未出现特异性标记。n 结论:18F-FINH-Me可能是一种有效检测脑内Aβ斑块的PET显像剂。n “,”Objective:To synthesize a new β-amyloid (Aβ) radioactive tracer (2-((2-6-[ n 18F]fluoro-5-(methylamino)pyridin-2-yl)benzothiazol-6-yl)thio)ethanol (n 18F-FINH-Me), and evaluate its biological distribution and affinity to Aβ plaques.n Methods:18F-FINH-Me was synthesized by GE FN automated module, and the quality control and stability of n 18F-FINH-Me were determined with high performance liquid chromatography (HPLC). The biodistribution of n 18F-FINH-Me was observed in normal C57BL/6 mice (n n=25). MicroPET/CT imaging was performed in Alzheimer′s disease (AD) model mice(n n=5) and matched normal C57BL/6 mice(n n=5). The brain tissues of mice were taken for Aβ immunohistochemical staining.n 18F-FINH-Me autoradiography was performed in postmortem brain sections of one AD patient (female, 69 years old) and one healthy volunteer (female, 66 years old).n Results:The decay correction yield of n 18F-FINH-Me was (53±4)% (n n>20) with the radioactive purity of more than 98% (n n>20) and the specific activity of 79.90-122.00 GBq/μmol (n n=10). n 18F-FINH-Me was stable in phosphate buffered solution (PBS) after incubation for 4 h at room temperature. The biodistribution showed that n 18F-FINH-Me was mainly excreted through the liver and kidneys. MicroPET/CT imaging showed that n 18F-FINH-Me was obviously uptaken in the brain of AD mice. After injection for 1-2 min, the uptake of n 18F-FINH-Me reached the peak, and the elution speed was fast (whole brain standardized uptake value: 0.73±0.17 for 1 min, 0.31±0.06 for 30 min). The immunohistochemistry showed that there were abundant Aβ plaques in the brain of AD model mice but not in the normal C57BL/6 mice brain. The autoradiographic results showed thatn 18F-FINH-Me exhibited substantial plaque labeling in brain sections of one AD patient but not in the healthy volunteer.n Conclusion:18F-FINH-Me may be an effective PET agent for detecting Aβ plaques in brain.n
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