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

Svetlana I. Chefer, Andrew G. Horti, Kan Sam Lee, Andrei O. Koren, Douglas W. Jones, Julia G. Gorey, Jonathan M. Links, Alexey G. Mukhin, Daniel R. 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)
Pages (from-to)PL355-PL360
JournalLife Sciences
Volume63
Issue number25
DOIs
StatePublished - Nov 13 1998
Externally publishedYes

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

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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