Measurement of α4β2 nicotinic acetylcholine receptors with [123I]5-I-A-85380 SPECT

Masahiro Fujita, G. Tamagnan, S. S. Zoghbi, M. S. Al-Tikriti, R. M. Baldwin, J. P. Seibyl, R. B. Innis

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49 Scopus citations


Nicotinic acetylcholine receptors (nAChRs) play an important role in tobacco dependence and a potential therapeutic role in neuropsychiatric disorders such as Alzheimer's disease. [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380) is a new SPECT tracer that labels α4β2 nAChRs. The purpose of this study was to assess the usefulness of this tracer to measure regional nAChR binding in baboon brain using both a bolus/kinetic paradigm and also a bolus plus constant infusion/equilibrium paradigm. Methods: A pair of bolus/kinetic and bolus plus constant infusion/equilibrium studies was performed in each of 3 isoflurane-anesthetized baboons. Bolus studies were performed by intravenous injection of 191-226 MBq [123I]5-I-A-85380 and image acquisition for 289-367 min. The data were analyzed with 1- and 2-tissue compartment models. Bolus plus constant infusion/ equilibrium studies were performed by a bolus injection (74-132 MBq) followed by a 468- to 495-min infusion with a bolus/infusion ratio (B/I) of 4.8-5.0 h. The distribution volumes in the thalamus were measured in these 2 paradigms. To study whether the cerebellum was appropriate as a receptor-poor region, displacement studies were done in 2 baboons using the B/I paradigm with subcutaneous injection of (-)-cytisine (0.8 and 1.0 mg/kg). Results: The kinetics of this tracer was best described by the 1-tissue compartment model. The 2-compartment model showed poor identifiability of rate constants. The total (specific plus nondisplaceable compartments) distribution volumes (V(T)') agreed between bolus and B/I paradigms (average percentage difference in V(T)', 16.8%). (-)-Cytisine (0.8 and 1.0 mg/kg) displaced 70% and 72% of the radioactivity in the thalamus and 36% and 55% in the cerebellum, respectively, indicating that the latter was not appropriate as a receptor-poor region. Conclusion: These results show the feasibility of quantifying α4β2 nAChRs using [123I]5-I-A-85380 and support the use of V(T)' as an appropriate outcome measure.

Original languageEnglish (US)
Pages (from-to)1552-1560
Number of pages9
JournalJournal of Nuclear Medicine
Issue number9
StatePublished - Jan 1 2000


  • 3-[2(S)-2-azetidinylmethoxy]pyridine
  • Compartment analysis
  • Equilibrium analysis
  • Nicotinic receptors

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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