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

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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.

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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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Authors and Affiliations

  1. Department of Chemistry, University of Oslo, Oslo, Norway

    Bent W. Schoultz & Gjermund Henriksen

  2. Centre for Molecular Biology and Neuroscience & Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    Trine Hjornevik & Frode Willoch

  3. Department of Nuclear Medicine, Akershus University Hospital, Lørenskog, Norway

    Trine Hjornevik & Frode Willoch

  4. ABX Advanced Biochemical Compounds GmbH, Radeberg, Germany

    János Marton

  5. Basic Research Department, The Medical and Pharmacological Research Center Foundation, Hakui City, Ishikawa, Japan

    Akihiro Noda, Yoshihiro Murakami, Sosuke Miyoshi & Shintaro Nishimura

  6. Institute of Nuclear Medicine, University College of London, London, UK

    Erik Årstad

  7. Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675, Munich, Germany

    Alexander Drzezga & Gjermund Henriksen

  8. Clinical Research Department, The Medical and Pharmacological Research Center Foundation, Hakui City, Ishikawa, Japan

    Ichiro Matsunari

Authors
  1. Bent W. Schoultz
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  2. Trine Hjornevik
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  3. Frode Willoch
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  7. Sosuke Miyoshi
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  8. Shintaro Nishimura
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  9. Erik Årstad
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  10. Alexander Drzezga
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  11. Ichiro Matsunari
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  12. Gjermund Henriksen
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Corresponding author

Correspondence to Gjermund Henriksen.

Additional information

Bent W. Schoultz and Trine Hjornevik contributed equally.

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Schoultz, B.W., Hjornevik, T., Willoch, F. et al. Evaluation of the kappa-opioid receptor-selective tracer [11C]GR103545 in awake rhesus macaques. Eur J Nucl Med Mol Imaging 37, 1174–1180 (2010). https://doi.org/10.1007/s00259-010-1384-6

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  • DOI: https://doi.org/10.1007/s00259-010-1384-6

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