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

Dag Erlend Olberg, Kjetil Wessel Andressen, Finn Olav Levy, Jo Klaveness, Ira Haraldsen, Julie Sutcliffe

Research output: Contribution to journalArticle

5 Citations (Scopus)

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. Log P (Octanol/PBS pH 7.4) and serum stability of the compounds were investigated. The antagonists showed low nM affinity for the rat GnRH receptor. 18F-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.

Original languageEnglish (US)
Pages (from-to)1846-1850
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number7
DOIs
StatePublished - Apr 1 2014

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LHRH Receptors
Hormone Antagonists
Imaging techniques
Molecules
Rats
Octanols
Fluorine
In Vitro Techniques
Serum

Keywords

  • Fluorine-18
  • Gonadotropin-releasing hormone (GnRH) receptor antagonists
  • Luteinizing hormone releasing hormone (LHRH)
  • Positron emission tomography (PET)
  • Small molecule

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

Cite this

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. / Olberg, Dag Erlend; Andressen, Kjetil Wessel; Levy, Finn Olav; Klaveness, Jo; Haraldsen, Ira; Sutcliffe, Julie.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 7, 01.04.2014, p. 1846-1850.

Research output: Contribution to journalArticle

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