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

Andrew 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 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

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
Publication status	Published - Feb 1999
Externally published	Yes

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Keywords

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

ASJC Scopus subject areas

Cancer Research
Molecular Medicine
Radiology Nuclear Medicine and imaging

Cite this

Horti, A., Koren, A. O., Lee, K. S., Mukhin, A. G., Vaupel, D. B., Kimes, A. S., ... London, E. D. (1999). Radiosynthesis and preliminary evaluation of 5-[(123/125)I]iodo-3- (2(S)-azetidinylmethoxy)pyridine: A radioligand for nicotinic acetylcholine receptors. Nuclear Medicine and Biology, 26(2), 175-182. https://doi.org/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. / Horti, Andrew; 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, 02.1999, p. 175-182.

Research output: Contribution to journal › Article

Horti, Andrew ; 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.

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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.",

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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.

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10.1016/S0969-8051(98)00086-9