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

J Med Chem. 2023 Sep 14;66(17):12629-12644. doi: 10.1021/acs.jmedchem.3c01310. Epub 2023 Aug 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes*
  • Amines
  • Anhydrides
  • Animals
  • Fluorine Radioisotopes / chemistry
  • Positron-Emission Tomography
  • Radiopharmaceuticals*
  • Rats


  • Alkynes
  • Amines
  • Anhydrides
  • Radiopharmaceuticals
  • Fluorine Radioisotopes

Supplementary concepts

  • Ankyloblepharon filiforme adnatum