用于观察肿瘤中 STING 表达的 18F 标记脒苯并咪唑类似物

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
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*, 
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引用次数: 0

摘要

干扰素基因刺激器(STING)在介导 STING 依赖性 I 型干扰素产生方面起着关键作用,而 I 型干扰素对增强肿瘤排斥反应至关重要。可视化肿瘤微环境中的 STING 对 STING 相关治疗很有价值,但合适的 STING 成像探针却很有限。在这项研究中,我们开发了[18F]AlF-ABI,一种具有脒基苯并咪唑核心结构的新型 18F 标记剂,用于 B16F10 和 CT26 肿瘤中 STING 的正电子发射断层扫描(PET)成像。合成的[18F]AlF-ABI的衰变校正放射化学收率为38.0 ± 7.9%,放射化学纯度超过97%。该探针与 STING 的结合亲和力为纳摩尔级(KD = 35.6 nM)。给药后,[18F]AlF-ABI 在肿瘤部位迅速积累,在 B16F10 肿瘤中的吸收率明显高于 CT26 肿瘤,这与 STING 免疫荧光模式一致。体外细胞实验和体内阻断 PET 成像进一步验证了其特异性。这些研究结果表明,[18F]AlF-ABI有望成为观察肿瘤微环境中STING的有效制剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

18F-Labeled Amidobenzimidazole Analogue for Visualizing STING Expression in Tumor

18F-Labeled Amidobenzimidazole Analogue for Visualizing STING Expression in Tumor

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.

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来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
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.
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