Radiosynthesis and preliminary evaluation of 5-[(123/125)I]iodo-3- (2(S)-azetidinylmethoxy)pyridine: A radioligand for nicotinic acetylcholine receptors

Andrew G. Horti; Andrei O. Koren; Kan Sam Lee; Alexey G. Mukhin; D. Bruce Vaupel; Alane S. Kimes; Morgan Stratton; Edythe D. London

doi:10.1016/S0969-8051(98)00086-9

Radiosynthesis and preliminary evaluation of 5-[(123/125)I]iodo-3- (2(S)-azetidinylmethoxy)pyridine: A radioligand for nicotinic acetylcholine receptors

Andrew G. Horti, Andrei O. Koren, Kan Sam Lee, Alexey G. Mukhin, D. Bruce Vaupel, Alane S. Kimes, Morgan Stratton, Edythe D. London

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

Abstract

The radiochemical syntheses of 5-[¹²⁵I]iodo-3-(2(S)- azetidinylmethoxy)pyridine (5-[¹²⁵I]-iodo-A-85380, [¹²⁵I]1) and 5- [¹²³I]-iodo-A-85380, [¹²³I]1, were accomplished by radioiodination of 5-trimethylstannyl-3-((1-tert-butoxycarbonyl-2(S)- azetidinyl)methoxy)pyridine, 2, followed by acidic deprotection. Average radiochemical yields of [¹²⁵I]1 and [¹²³I]1 were 40-55%; and the average specific radioactivities were 1,700 and 7,000 mCi/μmol, respectively. Binding affinities of [¹²⁵I] 1 and [¹²³I] 1 in vitro (rat brain membranes) were each characterized by a K(d) value of 11 pM. Preliminary in vivo assay and ex vivo autoradiography of mouse brain indicated that [¹²⁵I]1 selectively labels nicotinic acetylcholine receptors (nAChRs) with very high affinity and specificity. These studies suggest that [¹²³I]1 may be useful as a radioligand for single photon emission computed tomography (SPECT) imaging of nAChRs.

Original language	English (US)
Pages (from-to)	175-182
Number of pages	8
Journal	Nuclear Medicine and Biology
Volume	26
Issue number	2
DOIs	https://doi.org/10.1016/S0969-8051(98)00086-9
State	Published - Feb 1 1999
Externally published	Yes

Keywords

A-85380
Acetylcholine
I
I
Nicotinic receptors
Radioiodination
Radiotracer
Receptor binding
SPECT

ASJC Scopus subject areas

Molecular Medicine
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1016/S0969-8051(98)00086-9

Fingerprint Dive into the research topics of 'Radiosynthesis and preliminary evaluation of 5-[(123/125)I]iodo-3- (2(S)-azetidinylmethoxy)pyridine: A radioligand for nicotinic acetylcholine receptors'. Together they form a unique fingerprint.

Cite this

Radiosynthesis and preliminary evaluation of 5-[(123/125)I]iodo-3- (2(S)-azetidinylmethoxy)pyridine : A radioligand for nicotinic acetylcholine receptors. / Horti, Andrew G.; Koren, Andrei O.; Lee, Kan Sam; Mukhin, Alexey G.; Vaupel, D. Bruce; Kimes, Alane S.; Stratton, Morgan; London, Edythe D.

In: Nuclear Medicine and Biology, Vol. 26, No. 2, 01.02.1999, p. 175-182.

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

Horti, Andrew G. ; Koren, Andrei O. ; Lee, Kan Sam ; Mukhin, Alexey G. ; Vaupel, D. Bruce ; Kimes, Alane S. ; Stratton, Morgan ; London, Edythe D. / Radiosynthesis and preliminary evaluation of 5-[(123/125)I]iodo-3- (2(S)-azetidinylmethoxy)pyridine : A radioligand for nicotinic acetylcholine receptors. In: Nuclear Medicine and Biology. 1999 ; Vol. 26, No. 2. pp. 175-182.

@article{3824ca70b695404293e9945578114a45,

title = "Radiosynthesis and preliminary evaluation of 5-[(123/125)I]iodo-3- (2(S)-azetidinylmethoxy)pyridine: A radioligand for nicotinic acetylcholine receptors",

abstract = "The radiochemical syntheses of 5-[125I]iodo-3-(2(S)- azetidinylmethoxy)pyridine (5-[125I]-iodo-A-85380, [125I]1) and 5- [123I]-iodo-A-85380, [123I]1, were accomplished by radioiodination of 5-trimethylstannyl-3-((1-tert-butoxycarbonyl-2(S)- azetidinyl)methoxy)pyridine, 2, followed by acidic deprotection. Average radiochemical yields of [125I]1 and [123I]1 were 40-55%; and the average specific radioactivities were 1,700 and 7,000 mCi/μmol, respectively. Binding affinities of [125I] 1 and [123I] 1 in vitro (rat brain membranes) were each characterized by a K(d) value of 11 pM. Preliminary in vivo assay and ex vivo autoradiography of mouse brain indicated that [125I]1 selectively labels nicotinic acetylcholine receptors (nAChRs) with very high affinity and specificity. These studies suggest that [123I]1 may be useful as a radioligand for single photon emission computed tomography (SPECT) imaging of nAChRs.",

keywords = "A-85380, Acetylcholine, I, I, Nicotinic receptors, Radioiodination, Radiotracer, Receptor binding, SPECT",

author = "Horti, {Andrew G.} and Koren, {Andrei O.} and Lee, {Kan Sam} and Mukhin, {Alexey G.} and Vaupel, {D. Bruce} and Kimes, {Alane S.} and Morgan Stratton and London, {Edythe D.}",

year = "1999",

month = feb,

day = "1",

doi = "10.1016/S0969-8051(98)00086-9",

language = "English (US)",

volume = "26",

pages = "175--182",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier Inc.",

number = "2",

}

TY - JOUR

T1 - Radiosynthesis and preliminary evaluation of 5-[(123/125)I]iodo-3- (2(S)-azetidinylmethoxy)pyridine

T2 - A radioligand for nicotinic acetylcholine receptors

AU - Horti, Andrew G.

AU - Koren, Andrei O.

AU - Lee, Kan Sam

AU - Mukhin, Alexey G.

AU - Vaupel, D. Bruce

AU - Kimes, Alane S.

AU - Stratton, Morgan

AU - London, Edythe D.

PY - 1999/2/1

Y1 - 1999/2/1

N2 - The radiochemical syntheses of 5-[125I]iodo-3-(2(S)- azetidinylmethoxy)pyridine (5-[125I]-iodo-A-85380, [125I]1) and 5- [123I]-iodo-A-85380, [123I]1, were accomplished by radioiodination of 5-trimethylstannyl-3-((1-tert-butoxycarbonyl-2(S)- azetidinyl)methoxy)pyridine, 2, followed by acidic deprotection. Average radiochemical yields of [125I]1 and [123I]1 were 40-55%; and the average specific radioactivities were 1,700 and 7,000 mCi/μmol, respectively. Binding affinities of [125I] 1 and [123I] 1 in vitro (rat brain membranes) were each characterized by a K(d) value of 11 pM. Preliminary in vivo assay and ex vivo autoradiography of mouse brain indicated that [125I]1 selectively labels nicotinic acetylcholine receptors (nAChRs) with very high affinity and specificity. These studies suggest that [123I]1 may be useful as a radioligand for single photon emission computed tomography (SPECT) imaging of nAChRs.

AB - The radiochemical syntheses of 5-[125I]iodo-3-(2(S)- azetidinylmethoxy)pyridine (5-[125I]-iodo-A-85380, [125I]1) and 5- [123I]-iodo-A-85380, [123I]1, were accomplished by radioiodination of 5-trimethylstannyl-3-((1-tert-butoxycarbonyl-2(S)- azetidinyl)methoxy)pyridine, 2, followed by acidic deprotection. Average radiochemical yields of [125I]1 and [123I]1 were 40-55%; and the average specific radioactivities were 1,700 and 7,000 mCi/μmol, respectively. Binding affinities of [125I] 1 and [123I] 1 in vitro (rat brain membranes) were each characterized by a K(d) value of 11 pM. Preliminary in vivo assay and ex vivo autoradiography of mouse brain indicated that [125I]1 selectively labels nicotinic acetylcholine receptors (nAChRs) with very high affinity and specificity. These studies suggest that [123I]1 may be useful as a radioligand for single photon emission computed tomography (SPECT) imaging of nAChRs.

KW - A-85380

KW - Acetylcholine

KW - I

KW - Nicotinic receptors

KW - Radioiodination

KW - Radiotracer

KW - Receptor binding

KW - SPECT

UR - http://www.scopus.com/inward/record.url?scp=0033019825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033019825&partnerID=8YFLogxK

U2 - 10.1016/S0969-8051(98)00086-9

DO - 10.1016/S0969-8051(98)00086-9

M3 - Article

C2 - 10100216

AN - SCOPUS:0033019825

VL - 26

SP - 175

EP - 182

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 2

ER -