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Evaluation of the kappa-opioid receptor-selective tracer [11C]GR103545 in awake rhesus macaques

  • Bent W. Schoultz
  • Trine Hjornevik
  • Frode Willoch
  • János Marton
  • Akihiro Noda
  • Yoshihiro Murakami
  • Sosuke Miyoshi
  • Shintaro Nishimura
  • Erik Årstad
  • Alexander Drzezga
  • Ichiro Matsunari
  • Gjermund Henriksen
Original Article

Abstract

Purpose

The recent development in radiosynthesis of the 11C-carbamate function increases the potential of [11C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor (κ-OR) with PET. In the present study, [11C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound.

Methods

Regional brain uptake kinetics of [11C]GR103545 was studied 0–120 min after injection. The binding affinity and opioid subtype selectivity of [11C]GR103545 was determined in cells transfected with cloned human opioid receptors.

Results

In vitro binding assays demonstrated a high affinity of GR103545 for κ-OR (Ki = 0.02 ± 0.01 nM) with excellent selectivity over μ-OR (6 × 102-fold) and) δ-OR (2 × 104-fold). PET imaging revealed a volume of distribution (VT) pattern consistent with the known distribution of κ-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum.

Conclusion

[11C]GR103545 is selective for κ-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET.

Keywords

Opioid receptor Kappa PET imaging 11GR103545 

Notes

Acknowledgement

Financial support was received from Klinikum rechts der Isar, Technische Universität München, KKF-grant 8764175, and the Norwegian Research Council.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Bent W. Schoultz
    • 1
  • Trine Hjornevik
    • 2
    • 3
  • Frode Willoch
    • 2
    • 3
  • János Marton
    • 4
  • Akihiro Noda
    • 5
  • Yoshihiro Murakami
    • 5
  • Sosuke Miyoshi
    • 5
  • Shintaro Nishimura
    • 5
  • Erik Årstad
    • 6
  • Alexander Drzezga
    • 7
  • Ichiro Matsunari
    • 8
  • Gjermund Henriksen
    • 1
    • 7
  1. 1.Department of ChemistryUniversity of OsloOsloNorway
  2. 2.Centre for Molecular Biology and Neuroscience & Institute of Basic Medical SciencesUniversity of OsloOsloNorway
  3. 3.Department of Nuclear MedicineAkershus University HospitalLørenskogNorway
  4. 4.ABX Advanced Biochemical Compounds GmbHRadebergGermany
  5. 5.Basic Research DepartmentThe Medical and Pharmacological Research Center FoundationHakui City, IshikawaJapan
  6. 6.Institute of Nuclear MedicineUniversity College of LondonLondonUK
  7. 7.Department of Nuclear Medicine, Klinikum rechts der IsarTechnische Universität MünchenMunichGermany
  8. 8.Clinical Research DepartmentThe Medical and Pharmacological Research Center FoundationHakui City, IshikawaJapan

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