[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 Radiotheranostics Translation Center (PRTC)

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

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10.1016/S0969-8051(01)00258-X

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@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 - https://www.scopus.com/pages/publications/0034746801

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

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