Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S,S)-[18F]FMeNER-D2

  • Akihiro Takano
  • Balázs Gulyás
  • Andrea Varrone
  • Ralph Paul Maguire
  • Christer Halldin
Original Article

DOI: 10.1007/s00259-009-1118-9

Cite this article as:
Takano, A., Gulyás, B., Varrone, A. et al. Eur J Nucl Med Mol Imaging (2009) 36: 1308. doi:10.1007/s00259-009-1118-9

Abstract

Purpose

In a previous PET study on norepinephrine transporter (NET) occupancy in the nonhuman primate brain, the relationship between NET occupancy and atomoxetine plasma concentration, and occupancies among different brain regions, were not demonstrated adequately. It may therefore be difficult to translate the results to the clinical situations. In the present study, the detailed change of NET occupancy was investigated among a wider range of doses in a more advanced manner.

Methods

Two rhesus monkeys were examined using a high-resolution PET system with (S,S)-[18F]FMeNER-D2 under baseline conditions and after steady-state infusion of different doses of atomoxetine (0.003 to 0.12 mg/kg per hour). NET occupancy of the thalamus, brainstem and anterior cingulate cortex was calculated using BPND obtained with the simplified reference tissue model.

Results

NET occupancy increased regionally and uniformly as the plasma concentration of atomoxetine increased. The estimated Kd value (the amount to occupy 50% of NET) in the thalamus was 16 ng/ml.

Conclusion

The results indicate that clinical doses of atomoxetine would occupy NET almost completely.

Keywords

Norepinephrine transporter occupancy Atomoxetine 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Akihiro Takano
    • 1
  • Balázs Gulyás
    • 1
  • Andrea Varrone
    • 1
  • Ralph Paul Maguire
    • 2
    • 3
  • Christer Halldin
    • 1
  1. 1.Department of Clinical Neuroscience, Psychiatry SectionKarolinska InstitutetStockholmSweden
  2. 2.Pfizer Global Research and DevelopmentNew LondonUSA
  3. 3.Novartis Institutes for BioMedical ResearchBaselSwitzerland

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