Zhendong Song, Yinlong Li, Kenneth Dahl, Ahmad Chaudhary, Zhenkun Sun, Xin Zhou, Jiahui Chen, Yabiao Gao, Jian Rong, Chunyu Zhao, Jimmy S Patel, Lee Collier, Chongzhao Ran, Chuangyan Zhai, Linqi Zhang, Ahmed Haider, Kim S Mühlfenzl, Hongjie Yuan, Charles S Elmore, Magnus Schou, Steven H Liang
{"title":"发现 18F 标记的 AZD5213 衍生物作为靶向组胺亚型-3 受体的新型正电子发射断层扫描 (PET) 放射配体。","authors":"Zhendong Song, Yinlong Li, Kenneth Dahl, Ahmad Chaudhary, Zhenkun Sun, Xin Zhou, Jiahui Chen, Yabiao Gao, Jian Rong, Chunyu Zhao, Jimmy S Patel, Lee Collier, Chongzhao Ran, Chuangyan Zhai, Linqi Zhang, Ahmed Haider, Kim S Mühlfenzl, Hongjie Yuan, Charles S Elmore, Magnus Schou, Steven H Liang","doi":"10.1002/cbic.202400655","DOIUrl":null,"url":null,"abstract":"<p><p>The histamine subtype 3 (H<sub>3</sub>) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H<sub>3</sub> receptor. In this study, we synthesized and evaluated the binding effects of [<sup>18</sup>F]H3-2404 and [<sup>18</sup>F]H3-2405 by modifying the structure of AZD5213, a selective H<sub>3</sub> antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non-specific distribution in rodent brain. Although these data suggest that [<sup>18</sup>F]H3-2404 and [<sup>18</sup>F]H3-2405 are unsuitable as PET tracers for brain imaging of the H<sub>3</sub> receptor, this study provides a valuable attempt for optimizing <sup>18</sup>F labeled radiotracers based on AZD5213.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Discovery of <sup>18</sup>F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype-3 Receptor.\",\"authors\":\"Zhendong Song, Yinlong Li, Kenneth Dahl, Ahmad Chaudhary, Zhenkun Sun, Xin Zhou, Jiahui Chen, Yabiao Gao, Jian Rong, Chunyu Zhao, Jimmy S Patel, Lee Collier, Chongzhao Ran, Chuangyan Zhai, Linqi Zhang, Ahmed Haider, Kim S Mühlfenzl, Hongjie Yuan, Charles S Elmore, Magnus Schou, Steven H Liang\",\"doi\":\"10.1002/cbic.202400655\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The histamine subtype 3 (H<sub>3</sub>) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H<sub>3</sub> receptor. In this study, we synthesized and evaluated the binding effects of [<sup>18</sup>F]H3-2404 and [<sup>18</sup>F]H3-2405 by modifying the structure of AZD5213, a selective H<sub>3</sub> antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non-specific distribution in rodent brain. Although these data suggest that [<sup>18</sup>F]H3-2404 and [<sup>18</sup>F]H3-2405 are unsuitable as PET tracers for brain imaging of the H<sub>3</sub> receptor, this study provides a valuable attempt for optimizing <sup>18</sup>F labeled radiotracers based on AZD5213.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/cbic.202400655\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/cbic.202400655","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Discovery of 18F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype-3 Receptor.
The histamine subtype 3 (H3) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H3 receptor. In this study, we synthesized and evaluated the binding effects of [18F]H3-2404 and [18F]H3-2405 by modifying the structure of AZD5213, a selective H3 antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non-specific distribution in rodent brain. Although these data suggest that [18F]H3-2404 and [18F]H3-2405 are unsuitable as PET tracers for brain imaging of the H3 receptor, this study provides a valuable attempt for optimizing 18F labeled radiotracers based on AZD5213.
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