Jingqi Wang, Tao Wang, Tiantian Mou, Tao Yang, Xu Gao, Xiaodan An, Biao Hu, Jinming Zhang, Xiaoli Zhang, Winnie Deuther-Conrad, Yiyun Huang, Hongmei Jia
{"title":"新型 18F 标记苯并咪唑酮类放射配体作为肿瘤成像的高选择性 Sigma-2 受体探针","authors":"Jingqi Wang, Tao Wang, Tiantian Mou, Tao Yang, Xu Gao, Xiaodan An, Biao Hu, Jinming Zhang, Xiaoli Zhang, Winnie Deuther-Conrad, Yiyun Huang, Hongmei Jia","doi":"10.1021/acs.jmedchem.4c01315","DOIUrl":null,"url":null,"abstract":"Novel sigma-2 (σ<sub>2</sub>) receptor ligands with benzimidazolone and 5,6-dimethoxyisoindoline as pharmacophores were designed and synthesized. Compound <b>4</b> exhibited low nanomolar affinity for the σ<sub>2</sub> receptors (<i>K</i><sub>i</sub>(σ<sub>2</sub>) = 2.30 nM) and high subtype selectivity (<i>K</i><sub>i</sub>(σ<sub>1</sub>)/<i>K</i><sub>i</sub>(σ<sub>2</sub>) > 1500). Radioligand [<sup>18</sup>F]<b>4</b> was prepared in radiochemical yields of 18 ± 7%, with >99% radiochemical purity and molar activity of 244 ± 136 GBq/μmol. Biodistribution and blocking studies in mice and small animal PET/CT imaging in rats indicated highly specific binding of [<sup>18</sup>F]<b>4</b> in organs known to express the σ<sub>2</sub> receptors. Small animal PET/CT imaging with [<sup>18</sup>F]<b>4</b> showed clear visualization of the tumors in subcutaneous A549 lung cancer and U87MG glioma xenografts, and intracranial orthotopic U87MG glioma models. Co-administration of CM398 with [<sup>18</sup>F]<b>4</b> significantly reduced activity uptake in the tumors, indicating that [<sup>18</sup>F]<b>4</b> specifically binds to the σ<sub>2</sub> receptors expressed in A549 and U87MG xenografts.","PeriodicalId":6,"journal":{"name":"ACS Applied Nano Materials","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel 18F-Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma-2 Receptor Probes for Tumor Imaging\",\"authors\":\"Jingqi Wang, Tao Wang, Tiantian Mou, Tao Yang, Xu Gao, Xiaodan An, Biao Hu, Jinming Zhang, Xiaoli Zhang, Winnie Deuther-Conrad, Yiyun Huang, Hongmei Jia\",\"doi\":\"10.1021/acs.jmedchem.4c01315\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Novel sigma-2 (σ<sub>2</sub>) receptor ligands with benzimidazolone and 5,6-dimethoxyisoindoline as pharmacophores were designed and synthesized. Compound <b>4</b> exhibited low nanomolar affinity for the σ<sub>2</sub> receptors (<i>K</i><sub>i</sub>(σ<sub>2</sub>) = 2.30 nM) and high subtype selectivity (<i>K</i><sub>i</sub>(σ<sub>1</sub>)/<i>K</i><sub>i</sub>(σ<sub>2</sub>) > 1500). Radioligand [<sup>18</sup>F]<b>4</b> was prepared in radiochemical yields of 18 ± 7%, with >99% radiochemical purity and molar activity of 244 ± 136 GBq/μmol. Biodistribution and blocking studies in mice and small animal PET/CT imaging in rats indicated highly specific binding of [<sup>18</sup>F]<b>4</b> in organs known to express the σ<sub>2</sub> receptors. Small animal PET/CT imaging with [<sup>18</sup>F]<b>4</b> showed clear visualization of the tumors in subcutaneous A549 lung cancer and U87MG glioma xenografts, and intracranial orthotopic U87MG glioma models. Co-administration of CM398 with [<sup>18</sup>F]<b>4</b> significantly reduced activity uptake in the tumors, indicating that [<sup>18</sup>F]<b>4</b> specifically binds to the σ<sub>2</sub> receptors expressed in A549 and U87MG xenografts.\",\"PeriodicalId\":6,\"journal\":{\"name\":\"ACS Applied Nano Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Nano Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.jmedchem.4c01315\",\"RegionNum\":2,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Nano Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.jmedchem.4c01315","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
Novel 18F-Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma-2 Receptor Probes for Tumor Imaging
Novel sigma-2 (σ2) receptor ligands with benzimidazolone and 5,6-dimethoxyisoindoline as pharmacophores were designed and synthesized. Compound 4 exhibited low nanomolar affinity for the σ2 receptors (Ki(σ2) = 2.30 nM) and high subtype selectivity (Ki(σ1)/Ki(σ2) > 1500). Radioligand [18F]4 was prepared in radiochemical yields of 18 ± 7%, with >99% radiochemical purity and molar activity of 244 ± 136 GBq/μmol. Biodistribution and blocking studies in mice and small animal PET/CT imaging in rats indicated highly specific binding of [18F]4 in organs known to express the σ2 receptors. Small animal PET/CT imaging with [18F]4 showed clear visualization of the tumors in subcutaneous A549 lung cancer and U87MG glioma xenografts, and intracranial orthotopic U87MG glioma models. Co-administration of CM398 with [18F]4 significantly reduced activity uptake in the tumors, indicating that [18F]4 specifically binds to the σ2 receptors expressed in A549 and U87MG xenografts.
期刊介绍：
ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.
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