High-yielding aqueous 18F-labeling of peptides via Al18F chelation

Bioconjug Chem. 2011 Sep 21;22(9):1793-803. doi: 10.1021/bc200175c. Epub 2011 Aug 9.


The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with a methylphenylacetic acid (MPAA) backbone, and its ability to form stable Al(18)F chelates were investigated. The organofluoroaluminates were easily accessible from the reaction of 1 and AlF(3). X-ray diffraction studies revealed aluminum at the center of a slightly distorted octahedron, with fluorine occupying one of the axial positions. The tert-butyl protected prochelator 7, which can be synthesized in one step, is useful for coupling to biomolecules on solid phase or in solution. High yield (55-89%) aqueous (18)F-labeling was achieved in 10-15 min with a tumor-targeting peptide 4 covalently linked to 1. Defluorination was not observed for at least 4 h in human serum at 37 °C. These results demonstrate the facile application of Al(18)F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aluminum / chemistry
  • Chelating Agents / chemistry*
  • Fluorine Radioisotopes / chemistry*
  • Haptens / chemistry
  • Heterocyclic Compounds / chemistry
  • Isotope Labeling / methods
  • Peptides / chemistry*
  • X-Ray Diffraction


  • 1,4,7-triazacyclononane-1,4-diacetate
  • Chelating Agents
  • Fluorine Radioisotopes
  • Haptens
  • Heterocyclic Compounds
  • Peptides
  • Aluminum