Site-Specific Radiofluorination of Biomolecules with 8-[(18)F]-Fluorooctanoic Acid Catalyzed by Lipoic Acid Ligase

ACS Chem Biol. 2016 Jun 17;11(6):1587-94. doi: 10.1021/acschembio.6b00172. Epub 2016 Mar 31.


New methodologies for site-specifically radiolabeling proteins with (18)F are required to generate high quality radiotracers for preclinical and clinical applications with positron emission tomography. Herein, we report an approach by which we use lipoic acid ligase (LplA) to conjugate [(18)F]-fluorooctanoic acid to an antibody fragment bearing the peptide substrate of LplA. The mild conditions of the reaction preserve antibody immunoreactivity, and the efficiency of LplA allows for >90% yield even with very small amounts of peptidic precursor (1-10 nmol). These features are advantageous compared to the current gold standard in the field. Moreover, the methodology introduces a new application for an important tool in chemical biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Caprylates / chemical synthesis
  • Caprylates / chemistry*
  • Escherichia coli Proteins / chemistry*
  • Fluorine Radioisotopes
  • HEK293 Cells
  • Halogenation
  • Humans
  • Immunoglobulin Fab Fragments / chemistry*
  • Ligases / chemistry*
  • Peptides / chemistry


  • Caprylates
  • Escherichia coli Proteins
  • Fluorine Radioisotopes
  • Immunoglobulin Fab Fragments
  • Peptides
  • lplA protein, E coli
  • 8-fluorooctanoic acid
  • Ligases