[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

doi:10.1016/S0969-8051(01)00258-X

[^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

Precision Radio-Theranostics Translational Laboratories (PRT2L)

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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 language	English
Pages (from-to)	911-921
Number of pages	11
Journal	Nuclear Medicine and Biology
Volume	28
Issue number	8
DOIs	https://doi.org/10.1016/S0969-8051(01)00258-X
State	Published - 2001

Keywords

Iodine-123
Nicotinic acetylcholine receptor
SPECT

Access to Document

10.1016/S0969-8051(01)00258-X

Cite this

@article{0b96277e6b614cd182ee5ab8cee8fb67,

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

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.",

keywords = "Iodine-123, Nicotinic acetylcholine receptor, SPECT",

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

note = "Funding Information: The authors thank Dr. T. K. Natarajan and Ms. Andrea Toulon-Carter, CNMT for their technical assistance. This work was supported by USPHS grant NCI CA 77349 (JLM) and Smokeless Tobacco Research Institute (DFW).",

year = "2001",

doi = "10.1016/S0969-8051(01)00258-X",

language = "English",

volume = "28",

pages = "911--921",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

number = "8",

}

TY - JOUR

T1 - [125/123I] 5-Iodo-3-pyridyl ethers

T2 - Syntheses and binding to neuronal nicotinic acetylcholine receptors

AU - Fan, Hong

AU - Scheffel, Ursula A.

AU - Rauseo, Paige

AU - Xiao, Yingxian

AU - Dogan, A. Semih

AU - Yokoi, Fuji

AU - Hilton, John

AU - Kellar, Kenneth J.

AU - Wong, Dean F.

AU - Musachio, John L.

N1 - Funding Information: The authors thank Dr. T. K. Natarajan and Ms. Andrea Toulon-Carter, CNMT for their technical assistance. This work was supported by USPHS grant NCI CA 77349 (JLM) and Smokeless Tobacco Research Institute (DFW).

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Iodine-123

KW - Nicotinic acetylcholine receptor

KW - SPECT

UR - http://www.scopus.com/inward/record.url?scp=0034746801&partnerID=8YFLogxK

U2 - 10.1016/S0969-8051(01)00258-X

DO - 10.1016/S0969-8051(01)00258-X

M3 - Article

C2 - 11711310

AN - SCOPUS:0034746801

SN - 0969-8051

VL - 28

SP - 911

EP - 921

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

IS - 8

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this