Synthesis and characterization of the two enantiomers of a chiral sigma-1 receptor radioligand:(S)-(+)-and(R)-(-)-[^(18)F]FBFP  

作　　者：Tao Wang Ying Zhang Xiaojun Zhang Leyuan Chen Mingqiang Zheng Jinming Zhang Peter Brust Winnie Deuther-Conrad Yiyun Huang Hongmei Jia 

机构地区：[1]Key Laboratory of Radiopharmaceuticals(Beijing Normal University),Ministry of Education,College of Chemistry,Beijing Normal University,Beijing 100875,China [2]Nuclear Medicine Department,The First Medical Center of Chinese PLA General Hospital,Beijing 100853,China [3]Institute of Radiation Medicine,Peking Union Medical College&Chinese Academy of Medical Sciences,Tianjin 300192,China [4]Yale PET Center,Department of Radiology and Biomedical Imaging,Yale University School of Medicine,New Haven,CT 06520-8048,United States [5]Helmholtz-Zentrum Dresden-Rossendorf,Institute of Radiopharmaceutical Cancer Research,Department of Neuroradiopharmaceuticals,Leipzig 04318,Germany [6]The Lübeck Institute of Experimental Dermatology,University Medical Center Schleswig-Holstein,Lubeck 23562.Germany

出　　处：《Chinese Chemical Letters》2022年第7期3543-3548,共6页中国化学快报（英文版）

基　　金：the financial support from Beijing Natural Science Foundation(No.7212203);National Natural Science Foundation of China(No.21876013)。

摘　　要：Racemic[^(18)F]FBFP([^(18)F]1)proved to be a potentσ_(1) receptor radiotracer with superior imaging properties.The pure enantiomers of unlabeled compounds(S)-and(R)-1 and the corresponding iodonium ylide precursors were synthesized and characterized.The two enantiomers(S)-1 and(R)-1 exhibited comparable high affinity forσ_(1) receptors and selectivity overσ_(2) receptors.The Ca^(2+) fluorescence assay indicated that(R)-1 behaved as an antagonist and(S)-1 as an agonist forσ_(1) receptors.The ^(18)F-labeled enantiomers(S)-and(R)-[^(18)F]1 were obtained in>99%enantiomeric purity from the corresponding enantiopure iodonium ylide precursors with radiochemical yield of 24.4%±2.6%and molar activity of 86–214 GBq/μmol.In ICR mice both(S)-and(R)-[^(18)F]1displayed comparable high brain uptake,brain-to-blood ratio,in vivo stability and binding specificity in the brain and peripheral organs.In micro-positron emission tomography(PET)imaging studies in rats,(S)-[^(18)F]1 exhibited faster clearance from the brain than(R)-[^(18)F]1,indicating different brain kinetics of the two enantiomers.Both(S)-and(R)-[^(18)F]1 warrant further evaluation in primates to translate a single enantiomer with more suitable kinetics for imaging theσ_(1) receptors in humans.

关 键 词：σ_(1)receptor ENANTIOMER Radiotracer Positron emission tomography FLUORINE-18 

分 类 号：R981[医药卫生—药品] O641.4[医药卫生—药学]