2-Fluoropyridine prosthetic compounds for the 18F labeling of bombesin analogues

Bioorg Med Chem Lett. 2013 Jul 1;23(13):3920-6. doi: 10.1016/j.bmcl.2013.04.060. Epub 2013 Apr 30.

Abstract

Acetylene-bearing 2-[(18)F]fluoropyridines [(18)F]FPy5yne and PEG-[(18)F]FPyKYNE were prepared via efficient nucleophilic heteroaromatic [(18)F]fluorination of their corresponding 2-trimethylammoniumpyrdinyl precursors. The prosthetic groups were conjugated to azide- and PEG3-modified bombesin(6-14) analogues via copper-catalyzed azide-alkyne cycloaddition couplings to yield mono- and di-mini-PEGylated ligands for PET imaging of the gastrin- releasing peptide receptor. The PEG3- and PEG2/PEG3-bearing (18)F peptides showed decreased lipophilicity relative to an analogous non-mini-PEGylated (18)F peptide. Assessment of water-soluble peptide pharmacokinetics and tumour-targeting capabilities in a mouse model of prostate cancer is currently underway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bombesin* / chemical synthesis
  • Bombesin* / chemistry
  • Disease Models, Animal
  • Fluorine Radioisotopes* / chemistry
  • Ligands
  • Male
  • Mice
  • Molecular Structure
  • Neoplasms, Experimental / diagnosis*
  • Positron-Emission Tomography
  • Prostatic Neoplasms / diagnosis*
  • Pyridines* / chemistry
  • Receptors, Bombesin / analysis*

Substances

  • 2-fluoropyridine
  • Fluorine Radioisotopes
  • Ligands
  • Pyridines
  • Receptors, Bombesin
  • Bombesin