Quantification of nicotinic acetylcholine receptors in human brain using [123I]5-I-A-85380 SPET

  • Masahiro Fujita
  • Masanori Ichise
  • Christopher H. van Dyck
  • Sami S. Zoghbi
  • Gilles Tamagnan
  • Alexey G. Mukhin
  • Ali Bozkurt
  • Nicholas Seneca
  • Dnyanesh Tipre
  • Christopher C. DeNucci
  • Hidehiro Iida
  • D. Bruce Vaupel
  • Andrew G. Horti
  • Andrei O. Koren
  • Alane S. Kimes
  • Edythe D. London
  • John P. Seibyl
  • Ronald M. Baldwin
  • Robert B. Innis
Original Article

DOI: 10.1007/s00259-003-1320-0

Cite this article as:
Fujita, M., Ichise, M., van Dyck, C.H. et al. Eur J Nucl Med Mol Imaging (2003) 30: 1620. doi:10.1007/s00259-003-1320-0

Abstract

The purpose of this study was to assess the utility of a new single-photon emission tomography ligand, [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), to measure regional nAChR binding in human brain. Six healthy nonsmoker subjects (two men and four women, age 33±15 years) participated in both a bolus (dose: 317±42 MBq) and a bolus plus constant infusion (dose of bolus: 98±32 MBq, B/I=6.7±2.6 h, total dose: 331±55 MBq) study. The study duration was 5–8 h and 14 h in the former and the latter, respectively. Nonlinear least-squares compartmental analysis was applied to bolus studies to calculate total (VT′) and specific (VS′) distribution volumes. A two-tissue compartment model was applied to identify VS′. VT′ was also calculated in B/I studies. In bolus studies, VT′ was well identified by both one- and two-tissue compartment models, with a coefficient of variation of less than 5% in most regions. The two-compartment model gave VT′ values of 51, 22, 27, 32, 20, 19, 20, and 17 ml cm−3 in thalamus, cerebellum, putamen, pons, and frontal, parietal, temporal, and occipital cortices, respectively. The two-compartment model did not identify VS′ well. B/I studies provided poor accuracy of VT′ measurement, possibly due to deviations from equilibrium conditions. These results demonstrate the feasibility of quantifying high-affinity type nAChRs using [123I]5-I-A-85380 in humans and support the use of VT′ measured by bolus studies.

Keywords

High-affinity type nicotinic receptors Compartmental modeling Equilibrium Distribution volume 

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Masahiro Fujita
    • 1
    • 2
  • Masanori Ichise
    • 1
  • Christopher H. van Dyck
    • 2
  • Sami S. Zoghbi
    • 1
    • 2
    • 3
  • Gilles Tamagnan
    • 2
  • Alexey G. Mukhin
    • 4
  • Ali Bozkurt
    • 2
  • Nicholas Seneca
    • 1
    • 2
  • Dnyanesh Tipre
    • 1
  • Christopher C. DeNucci
    • 1
  • Hidehiro Iida
    • 5
  • D. Bruce Vaupel
    • 4
  • Andrew G. Horti
    • 4
  • Andrei O. Koren
    • 4
    • 6
  • Alane S. Kimes
    • 4
  • Edythe D. London
    • 4
    • 6
    • 7
    • 8
  • John P. Seibyl
    • 3
    • 9
  • Ronald M. Baldwin
    • 1
  • Robert B. Innis
    • 1
    • 2
  1. 1.Molecular Imaging BranchNational Institute of Mental HealthBethesdaUSA
  2. 2.Department of PsychiatryYale University School of Medicine and VA Connecticut Healthcare SystemWest HavenUSA
  3. 3.Department of RadiologyYale University School of Medicine and VA Connecticut Healthcare SystemWest HavenUSA
  4. 4.Brain Imaging Center, Intramural Research ProgramNational Institute on Drug AbuseBaltimoreUSA
  5. 5.Department of Investigative RadiologyNational Cardiovascular Center Research InstituteOsakaJapan
  6. 6.Department of Psychiatry and Biobehavioral SciencesDavid Geffen School of Medicine, UCLALos AngelesUSA
  7. 7.Department of Molecular and Medical PharmacologyDavid Geffen School of Medicine, UCLALos AngelesUSA
  8. 8.The Brain Research InstituteDavid Geffen School of Medicine, UCLALos AngelesUSA
  9. 9.Institute for Neurodegenerative DisordersNew HavenUSA

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