The use of (18)F-2-fluorodeoxyglucose (FDG) to label antibody fragments for immuno-PET of pancreatic cancer.
The use of (18)F-2-fluorodeoxyglucose (FDG) to label antibody fragments for immuno-PET of pancreatic cancer.
复制标题
使用（18）F-2-氟脱氧葡萄糖（FDG）将胰腺癌免疫细胞的抗体片段标记。
DOI：
10.1021/acscentsci.5b00121
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发表时间：
2015-06-24
影响因子：
18.2
通讯作者：
Ploegh H
中科院分区：
文献类型：
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作者：
Rashidian M;Keliher E;Dougan M;Juras PK;Cavallari M;Wojtkiewicz GR;Jacobsen J;Edens JG;Tas JM;Victora G;Weissleder R;Ploegh H
我们使用分选酶介导的反应将反式环辛烯官能化的短肽安装到感兴趣的蛋白质上，然后与四嗪标记的-18F-2-脱氧氟葡萄糖（FDG）反应，生成用于正电子发射断层扫描（PET）成像的18F标记的抗体片段。该方法快速、稳健且具有位点特异性（放射化学产率> 25%，未进行衰变校正）。18F-2-脱氧氟葡萄糖的可用性避免了对用于产生碳-氟键的更复杂化学的需要。我们通过使用抗II类MHC单域抗体通过PET检测小鼠异位胰腺肿瘤来证明该方法的实用性。我们将宏观PET图像与肿瘤的微观双光子可视化相关联。我们的方法提供了容易获得18F标记的抗体及其片段的分子特异性水平，补充传统的18F-FDG成像。18F-2-脱氧氟葡萄糖与分选酶组合用于位点特异性标记抗体片段。一种新的小鼠II类MHC特异性18F标记的VHH不仅装饰淋巴器官，而且由于免疫细胞的存在还检测到异位胰腺肿瘤（1.5 mm）。1、2、3：淋巴结，4：胸腺，5：肿瘤。
We generated 18F-labeled antibody fragments for positron emission tomography (PET) imaging using a sortase-mediated reaction to install a trans-cyclooctene-functionalized short peptide onto proteins of interest, followed by reaction with a tetrazine-labeled-18F-2-deoxyfluoroglucose (FDG). The method is rapid, robust, and site-specific (radiochemical yields > 25%, not decay corrected). The availability of 18F-2-deoxyfluoroglucose avoids the need for more complicated chemistries used to generate carbon–fluorine bonds. We demonstrate the utility of the method by detecting heterotopic pancreatic tumors in mice by PET, using anti-Class II MHC single domain antibodies. We correlate macroscopic PET images with microscopic two-photon visualization of the tumor. Our approach provides easy access to 18F-labeled antibodies and their fragments at a level of molecular specificity that complements conventional 18F-FDG imaging. 18F-2-Deoxyfluoroglucose combined with sortase is used to site-specifically label antibody fragments. A new mouse Class II MHC specific 18F-labeled VHH not only decorated lymphoid organs but also detected a heterotopic pancreatic tumor (∼1.5 mm) due to the presence of immune cells. 1, 2, 3: lymph nodes, 4: thymus, 5: tumor.