In vivo imaging of adenosine A1 receptors in the human brain with [18F]CPFPX and positron emission tomography
In vivo imaging of adenosine A1 receptors in the human brain with [18F]CPFPX and positron emission tomography
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DOI：
10.1016/s1053-8119(03)00241-6
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发表时间：
2003-08-01
期刊：
影响因子：
5.7
通讯作者：
Zilles, K
中科院分区：
文献类型：
--
作者：
Bauer, A;Holschbach, MH;Zilles, K
A(1)腺苷受体(A(1)AR)在脑生理和病理中的重要作用使其成为活体成像的靶点。在这里，我们描述了A(1)ARs在活体人脑中的分布，这是由高度有效和选择性的A(1)AR拮抗剂8-cyclopentyl-3-(3-[F-18]fluoropropyl)-1-propylxanthine([F-18]CPFPX)首次实现的。活体数据显示脑内摄取迅速，在3.3+/-1.3分钟时达到2.9+/-0.6%注射剂量/升的峰值，随后逐渐被清除。与放射自显影结果一致的是，壳核和背内侧丘脑的受体密度较高。新皮质区域在结合[F-18]CPFPX方面存在区域差异，在颞叶、枕叶、顶叶和额叶的结合水平较高，而在感觉运动皮质的结合水平较低。小脑、中脑和脑干的配体蓄积量较低。[18F]CPFPX在中枢神经系统外代谢迅速，但代谢产物不能穿透血脑屏障。总之，在活体中应用[F-18]CPFPX，一种高效和选择性的PET配体，首次允许在活体人类大脑中进行A(1)ARs的成像。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
The important roles played by the A(1) adenosine receptor (A(1)AR) in brain physiology and pathology make this receptor a target for in vivo imaging. Here we describe the distribution of A(1)ARs in the living human brain with PET, made possible for the first time by the highly potent and selective A(1)AR antagonist 8-cyclopentyl-3-(3-[F-18]fluoropropyl)-1-propylxanthine ([F-18]CPFPX). In vivo data demonstrate a rapid cerebral uptake, peaking at 2.9 +/- 0.6% injected dose/liter at 3.3 +/- 1.3 min, followed by a gradual washout. Consistent with the results of autoradiography, high receptor densities occurred in the putamen and the mediodorsal thalamus. Neocortical regions showed regional differences in [F-18]CPFPX binding, with high accumulation in temporal > occipital > parietal > frontal lobes and a lower level of binding in the sensorimotor cortex. Ligand accumulation was low in cerebellum, midbrain, and brain stem. Metabolism of [18 F]CPFPX is rapid outside the central nervous system, but the metabolites do not penetrate the blood-brain barrier. In conclusion, in vivo application of [F-18]CPFPX, a highly potent and selective PET ligand, for the first time allows the imaging of A(1)ARs in the living human brain. (C) 2003 Elsevier Science (USA). All rights reserved.