[18F] JK-PSMA-16

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