Radiosynthesis and preliminary evaluation of 5-[123/125I]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)metho xy)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/mumol, respectively. Binding affinities of [125I]1 and [123I]1 in vitro (rat brain membranes) were each characterized by a Kd 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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[123I]5-IA demonstrates low nonspecific binding, acceptable dosimetry in human subjects, high brain uptake, and good test-retest reproducibility.
“This ligand demonstrates low nonspecific binding40 and has acceptable dosimetry in human subjects with high brain uptake41, 42 and good test-retest reproducibility43.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [40]
[123I]5-IA is a radioligand that has specificity for the agonist binding site on β2*-nAChRs.
“With the recent development of [ 123 I]5-IA-85380 ([ 123 I]5-IA), a radioligand that has specificity for the agonist binding site on  2 *- nAChRs (Musachio et al., 1998(Musachio et al., , 1999;;Horti et al., 1999)”
From Human Tobacco Smokers in Early Abstinence Have Higher Levels of β<sub>2</sub>* Nicotinic Acetylcholine Receptors than Nonsmokers (2006) · cites this paper as Horti et al., 1999
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Flores, C. M., Rogers, S. W., Pabreza, L. A., Wolfe, B. B., & Kellar, K. J. (1992) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)08832-7 · Cited by 880 · see citing works
Musachio, J. L., Scheffel, U., Finley, P. A., Zhan, Y., Mochizuki, T., Wagner, H. N., & Dannals, R. F. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00180-5 · Cited by 57 · see citing works
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Staley, J. K., Krishnan-Sarin, S., Cosgrove, K. P., Krantzler, E., Frohlich, E., Perry, E., Dubin, J. A., Estok, K., Brenner, E., Baldwin, R. M., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0546-06.2006 · Cited by 223 · see citing works
“…of [ 123I]5-IA-85380 ([ 123I]5-IA), a radioligand that has specificity for the agonist binding site on 2*- nAChRs (Musachio et al., 1998, 1999; Horti et al., 1999), it is now possible to measure this site in living smokers during acute abstinence from smoking and to determine the relationship…”
BackgroundSelf-citationFunctional brain imaging of tobacco use and dependence
BRODY, A. (2006) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2005.04.012 · Cited by 207 · see citing works
5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors
Mukhin, A. G., Gündisch, D., Horti, A. G., Koren, A. O., Tamagnan, G., Kimes, A. S., Chambers, J., Vaupel, D. B., King, S. L., Picciotto, M. R., et al. (2000) · Molecular Pharmacology · doi:10.1124/mol.57.3.642 · Cited by 173 · see citing works
Self-citationCosgrove, K. P., Batis, J., Bois, F., Maciejewski, P. K., Esterlis, I., Kloczynski, T., Stiklus, S., Krishnan-Sarin, S., O’Malley, S., Perry, E., et al. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.41 · Cited by 159 · see citing works
Heterogeneity of Nicotinic Cholinergic Receptors in Rat Superior Cervical and Nodose Ganglia
Mao, D., Yasuda, R. P., Fan, H., Wolfe, B. B., & Kellar, K. J. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027458 · Cited by 81 · see citing works
Kassiou, M., Eberl, S., Meikle, S. R., Birrell, A., Constable, C., Fulham, M. J., Wong, D. F., & Musachio, J. L. (2001) · Nuclear Medicine and Biology · doi:10.1016/s0969-8051(00)00206-7 · Cited by 58 · see citing works
Vaupel, D. B., Tella, S. R., Huso, D. L., Wagner, V. O., Mukhin, A. G., Chefer, S. I., Horti, A. G., London, E. D., Koren, A. O., & Kimes, A. S. (2005) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.073999 · Cited by 28 · see citing works
Self-citationFujita, M., Al‐Tikriti, M. S., Tamagnan, G., Zoghbi, S. S., Bozkurt, A., Baldwin, R. M., & Innis, R. B. (2003) · Synapse · doi:10.1002/syn.10194 · Cited by 24 · see citing works
Deuther‐Conrad, W., Wevers, A., Becker, G., Schildan, A., Patt, M., Sabri, O., Steinbach, J., & Brust, P. (2006) · Synapse · doi:10.1002/syn.20232 · Cited by 12 · see citing works
- Authors
- Horti, A. G., Koren, A. O., Lee, K. S., Mukhin, A. G., Vaupel, D. B., Kimes, A. S., Stratton, M., & London, E. D.
- Affiliations
- National Institute on Drug Abuse (US)
- National Institute of Mental Health (US)
- Corresponding author
- London, Edythe D
- Venue
- Nuclear Medicine and Biology
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 26
- Issue
- 2
- Pages
- 175-182
- ISSN
- 0969-8051 (ISSN-L)
- OpenAlex
- W2085918622
- Cited by
- 48
- References
- 2
- Citations by year
- 2019: 1 · 2017: 1 · 2016: 2 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nuclear Medicine and Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Chemical Reactions and Isotopes
- Keywords
- nicotinic acetylcholine receptors, radioligand synthesis, radioiodination, iodine-123, iodine-125, SPECT imaging, receptor binding affinity, autoradiography, rat brain membranes, mouse brain
- MeSH terms
- Animals, Autoradiography, Azetidines, Brain, Evaluation Studies as Topic, Iodine Radioisotopes, Male, Radiochemistry, Radioligand Assay, Rats, Inbred F344, Receptors, Nicotinic, Tissue Distribution, Molecular Structure, Tomography, Emission-Computed, Single-Photon, Mice, Rats
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