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

H. Fan, U. A. Scheffel, P. Rauseo, Y. Xiao, A. S. Dogan, F. Yokoi, J. Hilton, K. J. Kellar, Dean Foster Wong, J. 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 - 2001

Fingerprint

3-(2-(pyrrolidinyl)methoxy)pyridine
Ethers
Nicotinic Receptors
Ligands
Thalamus
Ether
A 85380
Affinity Labels
Frontal Lobe
Single-Photon Emission-Computed Tomography
Cerebellum
Radioactivity
Pharmacokinetics
Brain
pyridine

Keywords

  • Iodine-123
  • Nicotinic acetylcholine receptor
  • SPECT

ASJC Scopus subject areas

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

Cite this

Fan, H., Scheffel, U. A., Rauseo, P., Xiao, Y., Dogan, A. S., Yokoi, 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

[125/123I] 5-Iodo-3-pyridyl ethers : Syntheses and binding to neuronal nicotinic acetylcholine receptors. / Fan, H.; Scheffel, U. A.; Rauseo, P.; Xiao, Y.; Dogan, A. S.; Yokoi, F.; Hilton, J.; Kellar, K. J.; Wong, Dean Foster; Musachio, J. L.

In: Nuclear Medicine and Biology, Vol. 28, No. 8, 2001, p. 911-921.

Research output: Contribution to journalArticle

Fan, H, Scheffel, UA, Rauseo, P, Xiao, Y, Dogan, AS, Yokoi, F, Hilton, J, Kellar, KJ, Wong, DF & Musachio, JL 2001, '[125/123I] 5-Iodo-3-pyridyl ethers: Syntheses and binding to neuronal nicotinic acetylcholine receptors', Nuclear Medicine and Biology, vol. 28, no. 8, pp. 911-921. https://doi.org/10.1016/S0969-8051(01)00258-X
Fan, H. ; Scheffel, U. A. ; Rauseo, P. ; Xiao, Y. ; Dogan, A. S. ; Yokoi, F. ; Hilton, J. ; Kellar, K. J. ; Wong, Dean Foster ; Musachio, J. L. / [125/123I] 5-Iodo-3-pyridyl ethers : Syntheses and binding to neuronal nicotinic acetylcholine receptors. In: Nuclear Medicine and Biology. 2001 ; Vol. 28, No. 8. pp. 911-921.
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