Synthesis and in vivo evaluation of a new PET radioligand for studying sigma-2 receptors

Michael Kassiou, Robert F. Dannals, Xiang Liu, Dean F. Wong, Hayden T. Ravert, Ursula A. Scheffel

Research output: Contribution to journalArticlepeer-review

Abstract

The cyclohexyl piperazine 1 (1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4- tetrahydro-naphthalen-1-yl)-propyl]-piperazine) has been shown to be a potent and selective sigma-2 receptor ligand. In the present study, we prepared [ 11C]1 by O-alkylation of the phenolic precursor 2 with [ 11C]CH3I. [11C]1 was obtained in a 29% non-decay corrected yield and specific activity of 9299 mCi/μmol calculated at end-of-synthesis. The biodistribution of [11C]1 in mouse brain demonstrated rapid and homogenous concentration in all brain structures, which included the cortex, thalamus, cerebellum and striatum. Co-administration of unlabelled 1 (1 mg/kg) or the sigma-2 selective ligand SM-21 (1 mg/kg) failed to show any significant inhibition of [11C]1 uptake in the mouse brain. The evaluation of this radioligand in vivo in the mouse clearly indicates that it does not possess the required properties for studying sigma-2 receptors in the brain using PET.

Original languageEnglish (US)
Pages (from-to)3623-3626
Number of pages4
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number11
DOIs
StatePublished - Jun 1 2005

Keywords

  • Carbon-11
  • PET
  • Radioligand
  • Sigma receptors

ASJC Scopus subject areas

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

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