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

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 x 102-fold) and δ-OR (2 x 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. (orig.)