6-[18F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors

Andrew G. Horti, Svetlana I. Chefer, Alexey G. Mukhin, Andrei O. Koren, Daniela Gündisch, Jonathan M. Links, Varughese Kurian, Robert F. Dannals, Edythe D. London

Research output: Contribution to journalArticle

Abstract

A novel positron emission tomography (PET) radiotracer, 6-[18F]fluoro- 3-(2(S)-azetidinyl-methoxy)pyridine (6-[18F]fluoro-A-85380, 6-[18F]FA) was synthesized by a no-carrier-added fluorination. In vitro 6-[18F]FA bound to nicotinic acetylcholine receptors (nAChRS), with very high affinity (K(d) 28 pM). In PET studies, 6-[18F]FA specifically labeled central nAChRs in the brain of the Rhesus monkey and demonstrated highest levels of accumulation of radioactivity in brain regions enriched with the α4β2 subtype of nAChR. 6-[18F]FA exhibited a target-to-non-target ratio (estimated as radio- activity in the thalamus to that in the cerebellum) of binding in primate brain similar to that previously determined for a labeled analog of epibatidine, [18F]FPH. In contrast to [18F]FPH, the novel tracer is expected to exhibit substantially less toxicity. Thus, the novel radioligand, 6-[18F]FA, appears to be a suitable candidate for imaging nAChRs in human brain.

Original languageEnglish (US)
Pages (from-to)463-469
Number of pages7
JournalLife Sciences
Volume67
Issue number4
DOIs
StatePublished - Jun 16 2000

Keywords

  • 6-[F]fluoro-3-(2(S)azetidinyl-methoxy)pyridine (6-[F]fluoro- A-85380, 6-[F]FA)
  • Nicotinic acetylcholine receptor
  • Positron emission tomography (nAChRs)

ASJC Scopus subject areas

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

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