5-(5-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin- 2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice

Yongjun Gao, Hayden T. Ravert, Heather Valentine, Ursula Scheffel, Paige Finley, Dean F. Wong, Robert F. Dannals, Andrew G. Horti

Research output: Contribution to journalArticle

Abstract

The radiosynthesis and in vivo evaluation of 5-(5-(6-[11C] methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [ 11C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [ 11C]CH3I afforded [11C]rac-1 in an average radiochemical yield of 30 ± 5% (n = 5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n = 5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [11C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.

Original languageEnglish (US)
Pages (from-to)3698-3702
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number12
DOIs
StatePublished - Jun 15 2012

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Keywords

  • Nicotinic acetylcholine receptors
  • Positron emission tomography
  • Radioligand
  • α7-nAChR

ASJC Scopus subject areas

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

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