Synthesis and biological evaluation of Tc-99m-cyclopentadienyltricarbonyl-technetium-labeled A-85380: An imaging probe for single-photon emission computed tomography investigation of nicotinic acetylcholine receptors in the brain

Hiroyuki Kimura, Masashi Ueda, Hidekazu Kawashima, Kenji Arimitsu, Yusuke Yagi, Hideo Saji

Research output: Contribution to journalArticle


We have designed (S)-(5-(azetidin-2-ylmethoxy)pyridine-3-yl)methyl cyclopentadienyltricarbonyl technetium carboxylate ([ 99m Tc]CPTT–A–E)with high affinity for nicotinic acetylcholine receptors (nAChRs)using (2(S)-azetidinylmethoxy)-pyridine (A-85380)as the lead compound to develop a Tc-99m-cyclopentadienyltricarbonyl-technetium ( 99m Tc)-labeled nAChR imaging probe. Because technetium does not contain a stable isotope, cyclopentadienyltricarbonyl rhenium (CPTR)was synthesized by coordinating rhenium, which is a homologous element having the same coordination structure as technetium. Further, the binding affinity to nAChR was evaluated. CPTR–A–E exhibited a high binding affinity to nAChR (K i = 0.55 nM). Through the radiosynthesis of [ 99m Tc]CPTT–A–E, an objective compound could be obtained with a radiochemical yield of 33% and a radiochemical purity of greater than 97%. In vitro autoradiographic study of the brain exhibited that the local nAChR density strongly correlated with the amount of [ 99m Tc]CPTT–A–E that was accumulated in each region of interest. Further, the in vivo evaluation of biodistribution revealed a higher accumulation of [ 99m Tc]CPTT–A–E in the thalamus (characterized by the high nAChR density)when compared with that in the cerebellum (characterized by the low nAChR density). Although additional studies will be necessary to improve the uptake of [ 99m Tc]CPTT–A–E to the brain, [ 99m Tc]CPTT–A–E met the basic requirements for nAChR imaging.

Original languageEnglish
JournalBioorganic and Medicinal Chemistry
Publication statusPublished - Jan 1 2019



  • A-85380
  • Bifunctional radiopharmaceutical
  • Cyclopentadienyltricarbonyl technetium
  • Nicotinic acetylcholine receptors
  • Single-photon emission computed tomography

ASJC Scopus subject areas

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

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