Copper-free click chemistry with the short-lived positron emitter fluorine-18

Org Biomol Chem. 2011 Nov 7;9(21):7393-9. doi: 10.1039/c1ob06034a. Epub 2011 Sep 22.


The copper-free strain-promoted click chemistry between (18)F-labeled aza-dibenzocyclooctyne [(18)F]FB-DBCO and various azides is described. [(18)F]FB-DBCO was prepared in 85% isolated radiochemical yield (decay-corrected) through acylation of amino aza-dibenzocyclooctyne 1 with N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB). [(18)F]FB-DBCO showed promising radiopharmacological profil with fast blood clearance as assessed with dynamic small animal PET studies. Metabolic stability of [(18)F]FB-DBCO was 60% of intact compound after 60 min post injection in normal Balb/C mice and blood clearance half-life was determined to be 53 s based on the time-activity-curve (TAC). Copper-free click chemistry was performed with various azides at low concentrations (1-2 μM) which differed in their structural complexity in different solvents (methanol, water, phosphate buffer and in bovine serum albumin (BSA) solution). Reaction proceeded best in methanol (>95% yield after 15 min at room temperature), whereas reaction in BSA required longer reaction times of 60 min and 40 °C upon completion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Alkynes / metabolism
  • Animals
  • Aza Compounds / chemistry*
  • Aza Compounds / metabolism
  • Azides / chemistry*
  • Azides / metabolism
  • Click Chemistry
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / metabolism


  • Alkynes
  • Aza Compounds
  • Azides
  • Fluorine Radioisotopes
  • Radiopharmaceuticals