Synthesis and in vitro evaluation of small-molecule [18F] labeled gonadotropin-releasing hormone (GnRH) receptor antagonists as potential PET imaging agents for GnRH receptor expression

Bioorg Med Chem Lett. 2014 Apr 1;24(7):1846-50. doi: 10.1016/j.bmcl.2014.02.002. Epub 2014 Feb 10.

Abstract

Two novel small molecule gonadotropin-releasing hormone (GnRH) receptor antagonists (12 and 13) of the furamide-class were synthesized and evaluated in vitro for their receptor binding affinities for the rat GnRH receptor. Radiolabeling with no carrier added fluorine-18 of the appropriate precursors was investigated in a one-step reaction. LogP (Octanol/PBS pH 7.4) and serum stability of the compounds were investigated. The antagonists showed low nM affinity for the rat GnRH receptor. (18)F-radiolabled compounds were obtained in high radiochemical purity (>95%) and specific activity (>75 GBq/μmol). These findings suggest this class of compounds holds promise as potential probes for PET targeting of GnRH-receptor expression.

Keywords: Fluorine-18; Gonadotropin-releasing hormone (GnRH) receptor antagonists; Luteinizing hormone releasing hormone (LHRH); Positron emission tomography (PET); Small molecule.

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

  • Animals
  • Dose-Response Relationship, Drug
  • Fluorine Radioisotopes / chemistry
  • HEK293 Cells
  • Humans
  • Molecular Structure
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacology*
  • Rats
  • Receptors, LHRH / antagonists & inhibitors*
  • Receptors, LHRH / biosynthesis
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Receptors, LHRH
  • Small Molecule Libraries