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

[Image: see text] (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.