Positron Emission Tomography Imaging Evaluation of a Novel 18F-Labeled Sigma-1 Receptor Radioligand in Cynomolgus Monkeys
Positron Emission Tomography Imaging Evaluation of a Novel 18F-Labeled Sigma-1 Receptor Radioligand in Cynomolgus Monkeys
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食蟹猴中新型 18F 标记 sigma-1 受体放射性配体的正电子发射断层扫描成像评估
DOI：
10.1021/acschemneuro.0c00171
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发表时间：
2020-06-03
影响因子：
5
通讯作者：
Huang, Yiyun
中科院分区：
文献类型：
--
作者：
Jia, Hongmei;Cai, Zhengxin;Huang, Yiyun
我们报告了一个方便的放射合成和第一个正电子发射断层扫描（PET）成像评价[F-18]FBFP作为一个强大的sigma-1（sigma（1））受体放射性配体具有有利的特点。[F-18]FBFP由碘鎓叶立德前体一步合成。在食蟹猴中，[F-18]FBFP显示出高脑摄取和适合定量分析的组织动力学。它表现出不均匀分布，杏仁核，海马，杏仁核和额叶皮层的区域分布容积（V-T）值较高。用σ（1）受体激动剂SA 4503（0.5 mg/kg）预处理显著降低猴脑中的放射性配体摄取（>95%），表明[F-18]FBFP在体内的高结合特异性。与（S）-[F-18]氟斯匹定相比，[F-18]FBFP具有更高的跨脑区的区域非置换结合电位（BPND）值。这些发现表明，[F-18]FBFP是一种非常有前途的PET放射性配体，可用于人体sigma（1）受体的成像和定量。
We report a convenient radiosynthesis and the first positron emission tomography (PET) imaging evaluation of [F-18]FBFP as a potent sigma-1 (sigma(1)) receptor radioligand with advantageous characteristics. [F-18]FBFP was synthesized in one step from an iodonium ylide precursor. In cynomolgus monkeys, [F-18]FBFP displayed high brain uptake and suitable tissue kinetics for quantitative analysis. It exhibited heterogeneous distribution with higher regional volume of distribution (V-T) values in the amygdala, hippocampus, insula, and frontal cortex. Pretreatment with the sigma(1) receptor agonist SA4503 (0.5 mg/kg) significantly reduced radioligand uptake in the monkey brain (>95%), indicating high binding specificity of [F-18]FBFP in vivo. Compared with (S)-[F-18]fluspidine, [F-18]FBFP possessed higher regional nondisplaceable binding potential (BPND) values across the brain regions. These findings demonstrate that [F-18]FBFP is a highly promising PET radioligand for imaging and quantification of sigma(1) receptors in humans.