Evaluation of radioiodinated 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine as a ligand for SPECT investigations of brain nicotinic acetylcholine receptors

Hideo Saji, Mikako Ogawa, Masashi Ueda, Yasuhiko Iida, Yasuhiro Magata, Akiko Tominaga, Hidekazu Kawashima, Youji Kitamura, Masaki Nakagawa, Yasushi Kiyono, Takahiro Mukai

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29 Citations (Scopus)


5-Iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA), an A-85380 analog iodinated at the 5-position of the pyridine ring, was evaluated as a radiopharmaceutical for investigating brain nicotinic acethylcholine receptors (nAChRs) by single photon emission computed tomography (SPECT). [123/125I]5IA was synthesized by the iododestannylation reaction under no-carrier-added conditions and purified by high-performance liquid chromatography (HPLC) with high radiochemical yield (50%), high radiochemical purity (> 98%), and high specific radioactivity (> 55 GBq/μmol). The binding affinity of 5IA for brain nAChRs was measured in terms of displacement of [3H]cytisine and [125I]5IA from binding sites in rat cortical membranes. The binding data revealed that the affinity of 5IA was the same as that of A-85380 and more than seven fold higher than that of (-)-nicotine, and that 5IA bound selectively to the α4β2 nAChR subtype. Biodistribution studies in rats indicated that the brain uptake of [125I]5IA was rapid and profound. Regional cerebral distribution studies in rats demonstrated that the accumulation of [125I]5IA was consistent with the density of high affinity nAChRs with highest uptake observed in the nAChR-rich thalamus, moderate uptake in the cortex and lowest uptake in the cerebellum. Administration of the nAChR agonists (-)-cytisine and (-)-nicotine reduced the uptake of [125I]5IA in all regions studied with most pronounced reduction in the thalamus, and resulted in similar levels of radioactivity throughout the brain. [125I]5IA binding sites were shown to be saturable with unlabeled 5IA. Behavioral studies in mice demonstrated that 5IA did not show signs of behavioral toxicity. Furthermore, SPECT studies with [123I]5IA in the common marmoset demonstrated appropriate brain uptake and regional localization for a high-affinity nAChR imaging radiopharmaceutical. These results suggested that [123I]5IA is a promising radiopharmaceutical for SPECT studies of central nAChRs in human subjects.

Original languageEnglish
Pages (from-to)189-200
Number of pages12
JournalAnnals of nuclear medicine
Issue number3
Publication statusPublished - 2002
Externally publishedYes


  • 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine
  • Brain
  • Nicotinic acethylcholine receptor
  • Radioiodination
  • Single photon emission computed tomography

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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