放射性合成20-[18F]氟花生四烯酸用于PET-MR成像:ApoE4-TR小鼠的生物学评价

Juno Van Valkenburgh , Marlon Vincent V. Duro , Erica Burnham , Quan Chen , Shaowei Wang , Jenny Tran , Bilal E. Kerman , Sung Hee Hwang , Xiaodan Liu , Naomi S. Sta. Maria , Francesca Zanderigo , Etienne Croteau , Stanley I. Rapoport , Stephen C. Cunnane , Russell E. Jacobs , Hussein N. Yassine , Kai Chen
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引用次数: 2

摘要

脑花生四烯酸(AA)代谢失调与慢性炎症有关,受载脂蛋白E4 (APOE4)基因型的影响,APOE4基因型是迟发性阿尔茨海默病(AD)最强的遗传危险因素。可视化AA在大脑中的摄取和分布可以深入了解神经炎症和AD的发病机制。在这里,我们提出了一种新的合成和放射性合成20-[18F]氟花生四烯酸([18F]- faa),用于PET成像,使用汇聚路径和一罐,单纯化放射性标记程序,并证明其在人类ApoE4靶向替代(ApoE4- tr)小鼠中的脑摄取。通过对星形胶质细胞p38磷酸化的检测,我们发现ω位AA的氟化没有显著改变其在细胞中的生化作用。通过多种方法估算[18F]-FAA的脑融合系数(K*),方法是使用来自心脏右心室的图像衍生输入函数作为动脉输入函数的代理,并通过动态PET-MR成像评估脑示踪剂浓度。这种新的合成方法将促进[18F]-FAA的实际生产并允许其转化为临床应用,使脂质代谢失调的研究在神经退行性疾病的研究中更加可行。
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Radiosynthesis of 20-[18F]fluoroarachidonic acid for PET-MR imaging: Biological evaluation in ApoE4-TR mice

Dysreglulated brain arachidonic acid (AA) metabolism is involved in chronic inflammation and is influenced by apolipoprotein E4 (APOE4) genotype, the strongest genetic risk factor of late-onset Alzheimer's disease (AD). Visualization of AA uptake and distribution in the brain can offer insight into neuroinflammation and AD pathogenesis. Here we present a novel synthesis and radiosynthesis of 20-[18F]fluoroarachidonic acid ([18F]-FAA) for PET imaging using a convergent route and a one-pot, single-purification radiolabeling procedure, and demonstrate its brain uptake in human ApoE4 targeted replacement (ApoE4-TR) mice. By examining p38 phosphorylation in astrocytes, we found that fluorination of AA at the ω-position did not significantly alter its biochemical role in cells. The brain incorporation coefficient (K*) of [18F]-FAA was estimated via multiple methods by using an image-derived input function from the right ventricle of the heart as a proxy of the arterial input function and brain tracer concentrations assessed by dynamic PET-MR imaging. This new synthetic approach should facilitate the practical [18F]-FAA production and allow its translation into clinical use, making investigations of dysregulation of lipid metabolism more feasible in the study of neurodegenerative diseases.

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来源期刊
Prostaglandins, leukotrienes, and essential fatty acids
Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism
CiteScore
5.30
自引率
0.00%
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0
审稿时长
64 days
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