Derivatives of dibenzothiophene for positron emission tomography imaging of α7-nicotinic acetylcholine receptors

Yongjun Gao, Kenneth J. Kellar, Robert P. Yasuda, Thao Tran, Yingxian Xiao, Robert F. Dannals, Andrew G. Horti

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A new series of derivatives of 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl) dibenzo[b,d]thiophene 5,5-dioxide with high binding affinities and selectivity for α7-nicotinic acetylcholine receptors (α7-nAChRs) (Ki = 0.4-20 nM) has been synthesized for positron emission tomography (PET) imaging of α7-nAChRs. Two radiolabeled members of the series [18F]7a (Ki = 0.4 nM) and [18F]7c (Ki = 1.3 nM) were synthesized. [18F]7a and [18F]7c readily entered the mouse brain and specifically labeled α7-nAChRs. The α7-nAChR selective ligand 1 (SSR180711) blocked the binding of [18F]7a in the mouse brain in a dose-dependent manner. The mouse blocking studies with non-α7-nAChR central nervous system drugs demonstrated that [ 18F]7a is highly α7-nAChR selective. In agreement with its binding affinity the binding potential of [18F]7a (BPND = 5.3-8.0) in control mice is superior to previous α7-nAChR PET radioligands. Thus, [18F]7a displays excellent imaging properties in mice and has been chosen for further evaluation as a potential PET radioligand for imaging of α7-nAChR in non-human primates.

Original languageEnglish (US)
Pages (from-to)7574-7589
Number of pages16
JournalJournal of medicinal chemistry
Issue number19
StatePublished - Oct 10 2013


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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