Synthesis and evaluation of an 18F-labelled norbornene derivative for copper-free click chemistry reactions

Org Biomol Chem. 2013 Jun 21;11(23):3817-25. doi: 10.1039/c3ob40548f.

Abstract

The copper-free click chemistry reaction between norbornene and tetrazine species is known to proceed in a rapid, reliable and selective manner under mild conditions. Due to these attractive properties, this reaction has recently been explored as a generally applicable method of bioconjugation. Here, we report a convenient synthetic procedure towards a novel (18)F-labelled norbornene derivative ([(18)F]NFB) and have evaluated its ability to undergo strain-promoted copper-free click chemistry reactions with two model tetrazine species: an asymmetric dipyridyl tetrazine derivative (Tz) and a tetrazine thiourea-coupled stabilised bombesin peptide (TT-BBN). In both cases, [(18)F]NFB was found to undergo rapid and high-yielding click chemistry reactions. Furthermore, as reactions of this type could also potentially be used in vivo to facilitate the development of a novel pretargeting approach for tumour imaging and therapy, we have also assessed the radiopharmacological profile (bioavailability, biodistribution, blood clearance and metabolic stability) of [(18)F]NFB in normal BALB/c mice. This radiolabelled compound exhibits both high bioavailability and metabolic stability with approximately 90% remaining intact up to 30 min following administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bombesin / chemistry
  • Chemistry Techniques, Synthetic
  • Click Chemistry*
  • Copper
  • Drug Stability
  • Fluorine Radioisotopes
  • Isotope Labeling
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Norbornanes / chemical synthesis*
  • Norbornanes / chemistry*
  • Norbornanes / pharmacokinetics
  • Peptide Fragments / chemistry
  • Positron-Emission Tomography

Substances

  • Fluorine Radioisotopes
  • Norbornanes
  • Peptide Fragments
  • 2-norbornene
  • Copper
  • Bombesin