In vivo imaging of brain nicotinic acetylcholine receptors with 5- [123I]iodo-A-85380 using single photon emission computed tomography

Svetlana I. Chefer, Andrew Horti, Kan Sam Lee, Andrei O. Koren, Douglas W. Jones, Julia G. Gorey, Jonathan M Links, Alexey G. Mukhin, Daniel Weinberger, Edythe D. London

Research output: Contribution to journalArticle

Abstract

The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3'') in the thalamus, estimated from the (thalamic - cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 after cytisine administration, radioactivity in the thalamus was reduced by 84%, in the frontal cortex, by 76%, and in the basal ganglia, by 57% of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain.

Original languageEnglish (US)
JournalLife Sciences
Volume63
Issue number25
StatePublished - Nov 13 1998
Externally publishedYes

Fingerprint

Single photon emission computed tomography
Radioactivity
Nicotinic Receptors
Single-Photon Emission-Computed Tomography
Neuroimaging
Brain
Thalamus
Imaging techniques
Frontal Lobe
Basal Ganglia
Injections
Ligands
Subcutaneous Injections
Macaca mulatta
Cerebellum
Toxicity
Animals
Kinetics
5-iodo-3-(2-azetidinylmethoxy)pyridine
cytisine

Keywords

  • 5[I]iodo-3-(2(S)-azetidinylmethoxy)pyridine (5- [I]iodo-A-85380)
  • Nicotinic acetylcholine receptor
  • Rhesus monkey
  • Single photon emission computed tomography

ASJC Scopus subject areas

  • Pharmacology

Cite this

Chefer, S. I., Horti, A., Lee, K. S., Koren, A. O., Jones, D. W., Gorey, J. G., ... London, E. D. (1998). In vivo imaging of brain nicotinic acetylcholine receptors with 5- [123I]iodo-A-85380 using single photon emission computed tomography. Life Sciences, 63(25).

In vivo imaging of brain nicotinic acetylcholine receptors with 5- [123I]iodo-A-85380 using single photon emission computed tomography. / Chefer, Svetlana I.; Horti, Andrew; Lee, Kan Sam; Koren, Andrei O.; Jones, Douglas W.; Gorey, Julia G.; Links, Jonathan M; Mukhin, Alexey G.; Weinberger, Daniel; London, Edythe D.

In: Life Sciences, Vol. 63, No. 25, 13.11.1998.

Research output: Contribution to journalArticle

Chefer, Svetlana I. ; Horti, Andrew ; Lee, Kan Sam ; Koren, Andrei O. ; Jones, Douglas W. ; Gorey, Julia G. ; Links, Jonathan M ; Mukhin, Alexey G. ; Weinberger, Daniel ; London, Edythe D. / In vivo imaging of brain nicotinic acetylcholine receptors with 5- [123I]iodo-A-85380 using single photon emission computed tomography. In: Life Sciences. 1998 ; Vol. 63, No. 25.
@article{dfdc912b0dab4b1991203cb6373498d7,
title = "In vivo imaging of brain nicotinic acetylcholine receptors with 5- [123I]iodo-A-85380 using single photon emission computed tomography",
abstract = "The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3'') in the thalamus, estimated from the (thalamic - cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 after cytisine administration, radioactivity in the thalamus was reduced by 84{\%}, in the frontal cortex, by 76{\%}, and in the basal ganglia, by 57{\%} of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain.",
keywords = "5[I]iodo-3-(2(S)-azetidinylmethoxy)pyridine (5- [I]iodo-A-85380), Nicotinic acetylcholine receptor, Rhesus monkey, Single photon emission computed tomography",
author = "Chefer, {Svetlana I.} and Andrew Horti and Lee, {Kan Sam} and Koren, {Andrei O.} and Jones, {Douglas W.} and Gorey, {Julia G.} and Links, {Jonathan M} and Mukhin, {Alexey G.} and Daniel Weinberger and London, {Edythe D.}",
year = "1998",
month = "11",
day = "13",
language = "English (US)",
volume = "63",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "25",

}

TY - JOUR

T1 - In vivo imaging of brain nicotinic acetylcholine receptors with 5- [123I]iodo-A-85380 using single photon emission computed tomography

AU - Chefer, Svetlana I.

AU - Horti, Andrew

AU - Lee, Kan Sam

AU - Koren, Andrei O.

AU - Jones, Douglas W.

AU - Gorey, Julia G.

AU - Links, Jonathan M

AU - Mukhin, Alexey G.

AU - Weinberger, Daniel

AU - London, Edythe D.

PY - 1998/11/13

Y1 - 1998/11/13

N2 - The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3'') in the thalamus, estimated from the (thalamic - cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 after cytisine administration, radioactivity in the thalamus was reduced by 84%, in the frontal cortex, by 76%, and in the basal ganglia, by 57% of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain.

AB - The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3'') in the thalamus, estimated from the (thalamic - cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 after cytisine administration, radioactivity in the thalamus was reduced by 84%, in the frontal cortex, by 76%, and in the basal ganglia, by 57% of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain.

KW - 5[I]iodo-3-(2(S)-azetidinylmethoxy)pyridine (5- [I]iodo-A-85380)

KW - Nicotinic acetylcholine receptor

KW - Rhesus monkey

KW - Single photon emission computed tomography

UR - http://www.scopus.com/inward/record.url?scp=0032515198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032515198&partnerID=8YFLogxK

M3 - Article

C2 - 9870715

AN - SCOPUS:0032515198

VL - 63

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 25

ER -