Synthesis and evaluation of 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors

Y. S. Ding; N. Liu; T. Wang; J. Marecek; V. Garza; I. Ojima; J. S. Fowler

Synthesis and evaluation of 6-[¹⁸F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors

Y. S. Ding, N. Liu, T. Wang, J. Marecek, V. Garza, I. Ojima, J. S. Fowler

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

51 Scopus citations

Abstract

Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[¹⁸F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[¹⁸F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[¹⁸F]fluoro-A-85380. Preliminary compartative PET studies of 6-[¹⁸F]fluoro-A-85380 and 2-[¹⁸F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system. (C) 2000 Elsevier Science Inc.

Original language	English
Pages (from-to)	381-389
Number of pages	9
Journal	Journal of Inorganic Biochemistry
Volume	78
Issue number	3
State	Published - 29 Feb 2000
Externally published	Yes

Keywords

A-85380
ABT-594
F-18
Nicotinic acetylcholine receptors
Nucleophilic aromatic substitution
Positron emission tomography
Trimethylammonium

Cite this

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title = "Synthesis and evaluation of 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors",

abstract = "Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[18F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[18F]fluoro-A-85380. Preliminary compartative PET studies of 6-[18F]fluoro-A-85380 and 2-[18F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system. (C) 2000 Elsevier Science Inc.",

keywords = "A-85380, ABT-594, F-18, Nicotinic acetylcholine receptors, Nucleophilic aromatic substitution, Positron emission tomography, Trimethylammonium",

author = "Ding, {Y. S.} and N. Liu and T. Wang and J. Marecek and V. Garza and I. Ojima and Fowler, {J. S.}",

note = "Funding Information: This research was carried out at Brookhaven National Laboratory under contract DE-AC02-98CH10886 with the US Department of Energy and Office of Biological Environmental Research; and also supported by the National Institutes of Health (National Institute of Neurological Diseases and Stroke NS-15380). The authors are grateful for the assistance of D. Schlyer, R. Ferrieri, R. MacGregor, C. Shea, R. Carciello, N. Pappas, P. King, P. Carter, D. Alexoff, and D. Warner. ",

year = "2000",

month = feb,

day = "29",

language = "English",

volume = "78",

pages = "381--389",

journal = "Journal of Inorganic Biochemistry",

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TY - JOUR

T1 - Synthesis and evaluation of 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors

AU - Ding, Y. S.

AU - Liu, N.

AU - Wang, T.

AU - Marecek, J.

AU - Garza, V.

AU - Ojima, I.

AU - Fowler, J. S.

N1 - Funding Information: This research was carried out at Brookhaven National Laboratory under contract DE-AC02-98CH10886 with the US Department of Energy and Office of Biological Environmental Research; and also supported by the National Institutes of Health (National Institute of Neurological Diseases and Stroke NS-15380). The authors are grateful for the assistance of D. Schlyer, R. Ferrieri, R. MacGregor, C. Shea, R. Carciello, N. Pappas, P. King, P. Carter, D. Alexoff, and D. Warner.

PY - 2000/2/29

Y1 - 2000/2/29

N2 - Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[18F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[18F]fluoro-A-85380. Preliminary compartative PET studies of 6-[18F]fluoro-A-85380 and 2-[18F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system. (C) 2000 Elsevier Science Inc.

AB - Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[18F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[18F]fluoro-A-85380. Preliminary compartative PET studies of 6-[18F]fluoro-A-85380 and 2-[18F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system. (C) 2000 Elsevier Science Inc.

KW - A-85380

KW - ABT-594

KW - F-18

KW - Nicotinic acetylcholine receptors

KW - Nucleophilic aromatic substitution

KW - Positron emission tomography

KW - Trimethylammonium

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M3 - Article

C2 - 10938474

AN - SCOPUS:0034182449

SN - 0162-0134

VL - 78

SP - 381

EP - 389

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

IS - 3

ER -

Synthesis and evaluation of 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors

Abstract

Keywords

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Synthesis and evaluation of 6-[¹⁸F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors