{"title":"用于观察肿瘤中 STING 表达的 18F 标记脒苯并咪唑类似物","authors":"Jianyang Fang, Jingru Zhang, Lingxin Meng, Huifeng Li, Dongsheng Xia, Yaoxuan Wang, Hao Chen, Zhenhuan Liao, Rongqiang Zhuang, Yesen Li, Xianzhong Zhang* and Zhide Guo*, ","doi":"10.1021/acs.molpharmaceut.3c01201","DOIUrl":null,"url":null,"abstract":"<p >The stimulator of interferon genes (STING) is pivotal in mediating STING-dependent type I interferon production, which is crucial for enhancing tumor rejection. Visualizing STING within the tumor microenvironment is valuable for STING-related treatments, yet the availability of suitable STING imaging probes is limited. In this study, we developed [<sup>18</sup>F]AlF-ABI, a novel <sup>18</sup>F-labeled agent featuring an amidobenzimidazole core structure, for positron emission tomography (PET) imaging of STING in B16F10 and CT26 tumors. [<sup>18</sup>F]AlF-ABI was synthesized with a decay-corrected radiochemical yield of 38.0 ± 7.9% and radiochemical purity exceeding 97%. The probe exhibited a nanomolar STING binding affinity (<i>K</i><sub>D</sub> = 35.6 nM). Upon administration, [<sup>18</sup>F]AlF-ABI rapidly accumulated at tumor sites, demonstrating significantly higher uptake in B16F10 tumors compared to CT26 tumors, consistent with STING immunofluorescence patterns. Specificity was further validated through <i>in vitro</i> cell experiments and <i>in vivo</i> blocking PET imaging. These findings suggest that [<sup>18</sup>F]AlF-ABI holds promise as an effective agent for visualizing STING in the tumor microenvironment.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"21 4","pages":"1942–1951"},"PeriodicalIF":4.5000,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"18F-Labeled Amidobenzimidazole Analogue for Visualizing STING Expression in Tumor\",\"authors\":\"Jianyang Fang, Jingru Zhang, Lingxin Meng, Huifeng Li, Dongsheng Xia, Yaoxuan Wang, Hao Chen, Zhenhuan Liao, Rongqiang Zhuang, Yesen Li, Xianzhong Zhang* and Zhide Guo*, \",\"doi\":\"10.1021/acs.molpharmaceut.3c01201\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The stimulator of interferon genes (STING) is pivotal in mediating STING-dependent type I interferon production, which is crucial for enhancing tumor rejection. Visualizing STING within the tumor microenvironment is valuable for STING-related treatments, yet the availability of suitable STING imaging probes is limited. In this study, we developed [<sup>18</sup>F]AlF-ABI, a novel <sup>18</sup>F-labeled agent featuring an amidobenzimidazole core structure, for positron emission tomography (PET) imaging of STING in B16F10 and CT26 tumors. [<sup>18</sup>F]AlF-ABI was synthesized with a decay-corrected radiochemical yield of 38.0 ± 7.9% and radiochemical purity exceeding 97%. The probe exhibited a nanomolar STING binding affinity (<i>K</i><sub>D</sub> = 35.6 nM). Upon administration, [<sup>18</sup>F]AlF-ABI rapidly accumulated at tumor sites, demonstrating significantly higher uptake in B16F10 tumors compared to CT26 tumors, consistent with STING immunofluorescence patterns. Specificity was further validated through <i>in vitro</i> cell experiments and <i>in vivo</i> blocking PET imaging. These findings suggest that [<sup>18</sup>F]AlF-ABI holds promise as an effective agent for visualizing STING in the tumor microenvironment.</p>\",\"PeriodicalId\":52,\"journal\":{\"name\":\"Molecular Pharmaceutics\",\"volume\":\"21 4\",\"pages\":\"1942–1951\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-03-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c01201\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c01201","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
18F-Labeled Amidobenzimidazole Analogue for Visualizing STING Expression in Tumor
The stimulator of interferon genes (STING) is pivotal in mediating STING-dependent type I interferon production, which is crucial for enhancing tumor rejection. Visualizing STING within the tumor microenvironment is valuable for STING-related treatments, yet the availability of suitable STING imaging probes is limited. In this study, we developed [18F]AlF-ABI, a novel 18F-labeled agent featuring an amidobenzimidazole core structure, for positron emission tomography (PET) imaging of STING in B16F10 and CT26 tumors. [18F]AlF-ABI was synthesized with a decay-corrected radiochemical yield of 38.0 ± 7.9% and radiochemical purity exceeding 97%. The probe exhibited a nanomolar STING binding affinity (KD = 35.6 nM). Upon administration, [18F]AlF-ABI rapidly accumulated at tumor sites, demonstrating significantly higher uptake in B16F10 tumors compared to CT26 tumors, consistent with STING immunofluorescence patterns. Specificity was further validated through in vitro cell experiments and in vivo blocking PET imaging. These findings suggest that [18F]AlF-ABI holds promise as an effective agent for visualizing STING in the tumor microenvironment.
期刊介绍:
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.