7-[ 18 F]Fluoro-8-azaisatoic Anhydrides: Versatile Prosthetic Groups for the Preparation of PET Tracers.

Autor: Gröner B; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany.; Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany., Willmann M; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany., Donnerstag L; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany.; Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany., Urusova EA; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany.; Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany., Neumaier F; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany.; Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany., Humpert S; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany., Endepols H; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany.; Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany.; Faculty of Medicine and University Hospital Cologne, Department of Nuclear Medicine, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany., Neumaier B; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany.; Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany.; Max Planck Institute for Metabolism Research, Gleueler Straße 50, 50931 Cologne, Germany., Zlatopolskiy BD; Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße, 52428 Jülich, Germany.; Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany.; Max Planck Institute for Metabolism Research, Gleueler Straße 50, 50931 Cologne, Germany.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2023 Sep 14; Vol. 66 (17), pp. 12629-12644. Date of Electronic Publication: 2023 Aug 25.
DOI: 10.1021/acs.jmedchem.3c01310
Abstrakt: 18 F-Fluorination of sensitive molecules is often challenging, but can be accomplished under suitably mild conditions using radiofluorinated prosthetic groups (PGs). Herein, 1-alkylamino-7-[ 18 F]fluoro-8-azaisatoic anhydrides ([ 18 F]AFAs) are introduced as versatile 18 F-labeled building blocks that can be used as amine-reactive or "click chemistry" PGs. [ 18 F]AFAs were efficiently prepared within 15 min by "on cartridge" radiolabeling of readily accessible trimethylammonium precursors. Conjugation with a range of amines afforded the corresponding 2-alkylamino-6-[ 18 F]fluoronicotinamides in radiochemical conversions (RCCs) of 15-98%. In addition, radiolabeling of alkyne- or azide-functionalized precursors with azidopropyl- or propargyl-substituted [ 18 F]AFAs using Cu-catalyzed click cycloaddition afforded the corresponding conjugates in RCCs of 44-88%. The practical utility of the PGs was confirmed by the preparation of three 18 F-labeled PSMA ligands in radiochemical yields of 28-42%. Biological evaluation in rats demonstrated excellent in vivo stability of all three conjugates. In addition, one conjugate ([ 18 F]JK-PSMA-15) showed favorable imaging properties for high-contrast visualization of small PSMA-positive lesions.
Databáze: MEDLINE
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