Citation: Tao Wang, Ying Zhang, Xiaojun Zhang, Leyuan Chen, Mingqiang Zheng, Jinming Zhang, Peter Brust, Winnie Deuther-Conrad, Yiyun Huang, Hongmei Jia. Synthesis and characterization of the two enantiomers of a chiral sigma-1 receptor radioligand: (S)-(+)- and (R)-(-)-[¹⁸F]FBFP[J]. Chinese Chemical Letters, ;2022, 33(7): 3543-3548. doi: 10.1016/j.cclet.2022.03.099 shu

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

Tao Wang ^a ,
Ying Zhang ^a ,
Xiaojun Zhang ^b ,
Leyuan Chen ^c ,
Mingqiang Zheng ^d ,
Jinming Zhang ^{b, *,} ,
Peter Brust ^{e, #} ,
Winnie Deuther-Conrad ^e ,
Yiyun Huang ^{d, *,} ,
Hongmei Jia ^{a, *,}

a.
Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China
b.
Nuclear Medicine Department, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
c.
Institute of Radiation Medicine, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin 300192, China
d.
Yale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520-8048, United States
e.
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany

zhangjm301@163.com

henry.huang@yale.edu

hmjia@bnu.edu.cn

Received Date: 31 December 2021
Revised Date: 24 March 2022
Accepted Date: 24 March 2022
Available Online: 28 March 2022

Figures(9)

Racemic [¹⁸F]FBFP ([¹⁸F]1) proved to be a potent σ₁ 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 for σ₁ receptors and selectivity over σ₂ receptors. The Ca²⁺ fluorescence assay indicated that (R)-1 behaved as an antagonist and (S)-1 as an agonist for σ₁ receptors. The ¹⁸F-labeled enantiomers (S)- and (R)-[¹⁸F]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)-[¹⁸F]1 displayed 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)-[¹⁸F]1 exhibited faster clearance from the brain than (R)-[¹⁸F]1, indicating different brain kinetics of the two enantiomers. Both (S)- and (R)-[¹⁸F]1 warrant further evaluation in primates to translate a single enantiomer with more suitable kinetics for imaging the σ₁ receptors in humans.
- σ₁ receptor,
- Enantiomer,
- Radiotracer,
- Positron emission tomography,
- Fluorine-18
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沈阳化工大学材料科学与工程学院沈阳 110142

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

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通讯作者: 陈斌, bchen63@163.com

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