Evaluation of the kappa-opioid receptor-selective tracer [11C]GR103545 in awake rhesus macaques
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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.
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.
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.
[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.
KeywordsOpioid receptor Kappa PET imaging 11C GR103545
Financial support was received from Klinikum rechts der Isar, Technische Universität München, KKF-grant 8764175, and the Norwegian Research Council.
- 12.Noda A, Takamatsu H, Minoshima S, Tsukada H, Nishimura S. Determination of kinetic rate constants for 2-[18F]fluoro-2-deoxy-D-glucose and partition coefficient of water in conscious macaques and alterations in aging or anesthesia examined on parametric images with an anatomic standardization technique. J Cereb Blood Flow Metab 2003;23:1441–7.CrossRefPubMedGoogle Scholar
- 17.Simonin F, Gavériaux-Ruff C, Befort K, Matthes H, Lannes B, Micheletti G, et al. Kappa-opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology and expression pattern in the central nervous system. Proc Natl Acad Sci U S A 1995;92:7006–10.CrossRefPubMedGoogle Scholar