Synthesis and Biological Evaluation of Enantiomerically Pure ( R ) - and ( S ) - [18F]OF-NB1 for Imaging the GluN2B Subunit-Containing NMDA Receptors.

Autor: Korff M; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States.; Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstraße 48, Münster D-48149, Germany., Chaudhary A; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States., Li Y; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States., Zhou X; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States., Zhao C; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States., Rong J; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States., Chen J; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States., Xiao Z; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States., Elghazawy NH; Institute of Pharmacy, Department of Medicinal Chemistry, Martin-Luther-University Halle-Wittenberg, W.-Langenbeck-Str. 4, Halle 06120, Germany., Sippl W; Institute of Pharmacy, Department of Medicinal Chemistry, Martin-Luther-University Halle-Wittenberg, W.-Langenbeck-Str. 4, Halle 06120, Germany., Davenport AT; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, North Carolina 27157, United States., Daunais JB; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, North Carolina 27157, United States., Wang L; Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China., Abate C; Dipartimento di Farmacia-Scienze Del Farmaco, Università Degli Studi di Bari ALDO MORO, Via Orabona 4, Bari 70125, Italy., Ahmed H; Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 4, Zurich 8093, Switzerland., Crowe R; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States., Schmidt TJ; Institut für Pharmazeutische Biologie und Phytochemie, Westfälische Wilhelms-Universität Münster, Corrensstraße 48, Münster D-48149, Germany., Liang SH; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States., Ametamey SM; Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 4, Zurich 8093, Switzerland., Wünsch B; Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstraße 48, Münster D-48149, Germany., Haider A; Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, United States.; Department of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, Zurich 8091, Switzerland.; Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, United States.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2023 Dec 14; Vol. 66 (23), pp. 16018-16031. Date of Electronic Publication: 2023 Nov 18.
DOI: 10.1021/acs.jmedchem.3c01441
Abstrakt: GluN2B subunit-containing N- methyl-d-aspartate (NMDA) receptors have been implicated in various neurological disorders. Nonetheless, a validated fluorine-18 labeled positron emission tomography (PET) ligand for GluN2B imaging in the living human brain is currently lacking. The aim of this study was to develop a novel synthetic approach that allows an enantiomerically pure radiosynthesis of the previously reported PET radioligands ( R ) - [ 18 F]OF-NB1 and ( S ) - [ 18 F]OF-NB1 as well as to assess their in vitro and in vivo performance characteristics for imaging the GluN2B subunit-containing NMDA receptor in rodents. A novel synthetic approach was successfully developed, which allows for the enantiomerically pure radiosynthesis of ( R ) - [ 18 F]OF-NB1 and ( S ) - [ 18 F]OF-NB1 and the translation of the probe to the clinic. While both enantiomers were selective over sigma2 receptors in vitro and in vivo , ( R ) - [ 18 F]OF-NB1 showed superior GluN2B subunit specificity by in vitro autoradiography and higher volumes of distribution in the rodent brain by small animal PET studies.
Databáze: MEDLINE
Externí odkaz: