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

F-18-Fluorination of sensitive molecules is often challenging, but can be accomplished under suitably mild conditions using radiofluorinated prosthetic groups (PGs). Herein, 1-alkylamino-7-[F-18]fluoro-8-azaisatoic anhydrides ([F-18]AFAs) are introduced as versatile F-18-labeled building blocks that can be used as amine-reactive or "click chemistry" PGs. [F-18]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-[F-18]fluoronicotinamides in radiochemical conversions (RCCs) of 15-98%. In addition, radiolabeling of alkyne- or azide-functionalized precursors with azidopropyl- or propargyl-substituted [F-18]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 F-18-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 ([F-18]JK-PSMA-15) showed favorable imaging properties for high-contrast visualization of small PSMA-positive lesions.