5-[I-125/123]Iodo-3(2(S)-azetidinylmethoxy)pyridine, a radioiodinated analog of A-85380 for in vivo studies of central nicotinic acetylcholine receptors

John L. Musachio, Ursula Scheffel, Paige A. Finley, Yougen Zhan, Takao Mochizuki, Henry N. Wagner, Robert F. Dannals

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52 Scopus citations


The in vivo biodistribution profile of the novel nicotinic acetylcholine receptor (nAChR radioligand 5-[I-125/123]Iodo-3(2(S)-azetidinylmethoxy)pyridine, [I-125/123]-5-IA, in mouse brain was examined. This radiotracer displayed good brain penetration (3.1% of the injected dose (ID) in whole brain at 15 min post-radioligand injection). Radioligand distribution was consistent with the density of high affinity nAChRs with highest uptake observed in the nAChR-rich thalamus (14.9 %ID/g at 60 min), moderate uptake in cortex (8.5 %ID/g at 60 min), and lowest uptake in the cerebellum (2.4 %ID/g at 60 min). Pretreatment with several different nAChR agonists (A-85380, (-)-nicotine, cytisine) significantly inhibited [I-125]-5-IA binding in all brain regions studied (P < 0.01) demonstrating the high specificity of the radioligand for nAChRs. Blocking doses of the muscarinic antagonist scopolamine and the non-competitive nAChR channel blocker mecamylamine had no significant effect on radioactive uptake supporting the in vitro selectivity of [I-125]-5-IA for the nAChR component of the cholinergic system. [I-125]-5-IA binding sites were shown to be saturable with unlabeled 5-IA. With a relatively low acute toxicity (LD50 > 3 mg/kg via intravenous injection in mice) and high in vivo specificity and selectivity, 5-IA labeled with the imaging radionuclide I-123 may Drove useful for single photon emission computed tomography (SPECT) studies of nAChRs in human subjects.

Original languageEnglish (US)
Pages (from-to)PL351-PL357
JournalLife Sciences
Issue number22
StatePublished - Apr 24 1998


  • I-123
  • I-125
  • Nicotinic acetylcholine receptor
  • Single photon emission computed tomography

ASJC Scopus subject areas

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


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