[125/123I] 5-Iodo-3-pyridyl ethers: Syntheses and binding to neuronal nicotinic acetylcholine receptors

Hong Fan, Ursula A. Scheffel, Paige Rauseo, Yingxian Xiao, A. Semih Dogan, Fuji Yokoi, John Hilton, Kenneth J. Kellar, Dean F. Wong, John L. Musachio

Research output: Contribution to journalArticle

Abstract

Three 3-pyridyl ether nicotinic ligands-(S)-5-Iodo-3-[(2-pyrrolidinyl)-methoxy]pyridine (5-iodo-A-85865), (S)-5-Iodo-3-[1-(methyl)-2-pyrrolidinyl-methoxy]pyridine (5-Iodo-A-84543), and (S)-5-iodo-3-[1-methyl-(2-azetidinyl)-methoxy]pyridine (5-iodo-N-Me-A-85380) were labeled with I-125/I-123, and their ability to label high-affinity brain nicotinic acetylcholine receptors (nAChRs) was evaluated. The most promising ligand, [123/125I] 5-iodo-A-85865, showed approximately 65% inhibition of radioactivity uptake in thalamus in mice pretreated with cytisine. Preliminary SPECT imaging studies with [123I] 5-iodo-A-85865 revealed a distribution profile consistent with nAChRs (thalamus > frontal cortex > cerebellum) and a more rapid pharmacokinetic profile relative to azetidinyl 3-pyridyl ether based ligands.

Original languageEnglish (US)
Pages (from-to)911-921
Number of pages11
JournalNuclear Medicine and Biology
Volume28
Issue number8
DOIs
StatePublished - Jan 1 2001

Keywords

  • Iodine-123
  • Nicotinic acetylcholine receptor
  • SPECT

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Fan, H., Scheffel, U. A., Rauseo, P., Xiao, Y., Dogan, A. S., Yokoi, F., Hilton, J., Kellar, K. J., Wong, D. F., & Musachio, J. L. (2001). [125/123I] 5-Iodo-3-pyridyl ethers: Syntheses and binding to neuronal nicotinic acetylcholine receptors. Nuclear Medicine and Biology, 28(8), 911-921. https://doi.org/10.1016/S0969-8051(01)00258-X