Department of Chemistry, University of Oslo, Oslo, Norway.
Eur J Nucl Med Mol Imaging. 2010 Jun;37(6):1174-80. doi: 10.1007/s00259-010-1384-6. Epub 2010 Feb 16.
The recent development in radiosynthesis of the (11)C-carbamate function increases the potential of [(11)C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor (kappa-OR) with PET. In the present study, [(11)C]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 [(11)C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [(11)C]GR103545 was determined in cells transfected with cloned human opioid receptors.
In vitro binding assays demonstrated a high affinity of GR103545 for kappa-OR (K(i) = 0.02 +/- 0.01 nM) with excellent selectivity over mu-OR (6 x 10(2)-fold) and) delta-OR (2 x 10(4)-fold). PET imaging revealed a volume of distribution (V(T)) pattern consistent with the known distribution of kappa-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum.
[(11)C]GR103545 is selective for kappa-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET.
最近在（11）C-氨基甲酸酯功能的放射合成方面的发展增加了 [(11)C]GR103545 的潜力，在过去的十年中，[(11)C]GR103545 一直被认为是用于 PET 成像κ-阿片受体（κ-OR）的有前途的放射性示踪剂。在本研究中，在清醒的恒河猴中评估了 [(11)C]GR103545。进行了单独的研究以阐明该化合物的 OR 亚型选择性。
在注射后 0-120 分钟研究了 [(11)C]GR103545 的脑内摄取动力学。在转染了克隆人阿片受体的细胞中，确定了 [(11)C]GR103545 的结合亲和力和阿片受体亚型选择性。
体外结合实验表明，GR103545 对 κ-OR 具有高亲和力（K(i) = 0.02 +/- 0.01 nM），对 μ-OR（6 x 10(2)-fold）和 δ-OR（2 x 10(4)-fold）具有优异的选择性。PET 成像显示出与已知 κ-OR 分布一致的分布容积（V(T)）模式，纹状体=颞叶皮质>扣带回皮质>额皮质>顶叶皮质>丘脑>小脑。
[(11)C]GR103545 对 κ-OR 具有选择性，有望通过 PET 选择性地描绘和量化人类中的这种受体。
