Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , 2100 Copenhagen, Denmark.
Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen , Blegdamsvej 9, 2100 Copenhagen, Denmark.
ACS Chem Neurosci. 2017 Jan 18;8(1):22-27. doi: 10.1021/acschemneuro.6b00335. Epub 2016 Nov 17.
γ-Hydroxybutyric acid (GHB) is an endogenous neuroactive substance and proposed neurotransmitter with affinity for both low- and high-affinity binding sites. A radioligand with high and specific affinity toward the high-affinity GHB binding site would be a unique tool toward a more complete understanding of this population of binding sites. With its high specific affinity and monocarboxylate transporter (MCT1) mediated transport across the blood-brain barrier in pharmacological doses, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate. Here, we report the C-labeling and subsequent evaluation of [C]HOCPCA in a domestic pig, as a PET-radioligand for visualization of the high-affinity GHB binding sites in the live pig brain. To investigate the regional binding of HOCPCA in pig brain prior to in vivo PET studies, in vitro quantitative autoradiography on sections of pig brain was performed using [H]HOCPCA. In vivo evaluation of [C]HOCPCA showed no brain uptake, possibly due to a limited uptake of HOCPCA by the MCT1 transporter at tracer doses of [C]HOCPCA.
γ-羟基丁酸（GHB）是一种内源性神经活性物质和拟神经递质，对低亲和性和高亲和性结合位点均具有亲和力。一种对高亲和性 GHB 结合位点具有高亲和性和特异性的放射性配体将是更全面地了解该结合位点群体的独特工具。由于其具有高特异性亲和力和单羧酸转运蛋白（MCT1）介导的在药理学剂量下穿过血脑屏障的转运，3-羟基环戊-1-烯羧酸（HOCPCA）似乎是一种合适的正电子发射断层扫描（PET）放射性示踪剂候选物。在这里，我们报告了 [C]HOCPCA 在国内猪中的 C 标记及其随后的评估，作为一种 PET 放射性配体，用于可视化活猪脑中的高亲和性 GHB 结合位点。为了在体内 PET 研究之前研究 HOCPCA 在猪脑中的区域结合，使用 [H]HOCPCA 在猪脑切片上进行了体外定量放射自显影。[C]HOCPCA 的体内评估显示没有脑摄取，这可能是由于在 [C]HOCPCA 的示踪剂量下，MCT1 转运体对 HOCPCA 的摄取有限。
