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
{"title":"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","authors":"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","doi":"10.1016/j.plefa.2022.102510","DOIUrl":null,"url":null,"abstract":"<div><p>Dysreglulated brain arachidonic acid (AA) metabolism is involved in chronic inflammation and is influenced by apolipoprotein E4 (<em>APOE4</em>) 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-[<sup>18</sup>F]fluoroarachidonic acid ([<sup>18</sup>F]-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 (<em>K</em>*) of [<sup>18</sup>F]-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 [<sup>18</sup>F]-FAA production and allow its translation into clinical use, making investigations of dysregulation of lipid metabolism more feasible in the study of neurodegenerative diseases.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Radiosynthesis of 20-[18F]fluoroarachidonic acid for PET-MR imaging: Biological evaluation in ApoE4-TR mice\",\"authors\":\"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\",\"doi\":\"10.1016/j.plefa.2022.102510\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Dysreglulated brain arachidonic acid (AA) metabolism is involved in chronic inflammation and is influenced by apolipoprotein E4 (<em>APOE4</em>) 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-[<sup>18</sup>F]fluoroarachidonic acid ([<sup>18</sup>F]-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 (<em>K</em>*) of [<sup>18</sup>F]-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 [<sup>18</sup>F]-FAA production and allow its translation into clinical use, making investigations of dysregulation of lipid metabolism more feasible in the study of neurodegenerative diseases.</p></div>\",\"PeriodicalId\":94179,\"journal\":{\"name\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2022-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0952327822001223\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins, leukotrienes, and essential fatty acids","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0952327822001223","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.