Design, synthesis, and validation of Axl-targeted monoclonal antibody probe for microPET imaging in human lung cancer xenograft.
Design, synthesis, and validation of Axl-targeted monoclonal antibody probe for microPET imaging in human lung cancer xenograft.
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DOI：
10.1021/mp500307t
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发表时间：
2014-11-03
影响因子：
4.9
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Liu S;Li D;Guo J;Canale N;Li X;Liu R;Krasnoperov V;Gill PS;Conti PS;Shan H;Li Z
越来越多的实验证据表明，致癌受体酪氨酸激酶Axl的过度表达在各种类型的癌症的肿瘤发生和转移中起关键作用。本研究的目的是设计一种基于单克隆抗体h173的新型成像探针，用于人肺癌Axl表达的microPET成像。双功能螯合剂DOTA与h173偶联，然后用64 Cu进行放射性标记。DOTA-h173与Axl受体的结合首先通过使用人肺癌细胞系的细胞摄取测定和流式细胞术分析来评估。通过微PET成像和Axl阳性A549肿瘤中的离体组织学研究进一步评估探针64 Cu-DOTA-h173。体外细胞实验表明，Axl探针64 Cu-DOTA-h173与A549细胞具有高度的免疫反应性。Western blot分析证实Axl在A549细胞系中高度表达。对于microPET成像，与NCI-H249异种移植物（阴性对照模型）相比，A549异种移植物显示出显著更高的64 Cu-DOTA-h173摄取。此外，A549中的64 Cu-DOTA-h173摄取显著高于64 Cu-DOTA-hIgG。免疫荧光染色与体内micro-PET成像结果一致。总之，64 Cu-DOTA-h173可以潜在地用作Axl表达的非侵入性成像的探针，其可以收集关于肿瘤对Axl靶向治疗干预的反应的重要信息。
Accumulating experimental evidence indicates that overexpression of the oncogenic receptor tyrosine kinase, Axl, plays a key role in the tumorigenesis and metastasis of various types of cancer. The objective of this study is to design a novel imaging probe based on the monoclonal antibody, h173, for microPET imaging of Axl expression in human lung cancer. A bifunctional chelator, DOTA, was conjugated to h173, followed by radiolabeling with 64Cu. The binding of DOTA-h173 to the Axl receptor was first evaluated by a cell uptake assay and flow cytometry analysis using human lung cancer cell lines. The probe 64Cu-DOTA-h173 was further evaluated by microPET imaging, and ex vivo histology studies in the Axl-positive A549 tumors. In vitro cellular study showed that Axl probe, 64Cu-DOTA-h173, was highly immuno-reactive with A549 cells. Western blot analysis confirmed that Axl is highly expressed in the A549 cell line. For microPET imaging, the A549 xenografts demonstrated a significantly higher 64Cu-DOTA-h173 uptake compared to the NCI-H249 xenograft (a negative control model). Furthermore, 64Cu-DOTA-h173 uptake in A549 is significantly higher than that of 64Cu-DOTA-hIgG. Immuno-fluorescence staining was consistent with the in vivo micro-PET imaging results. In conclusion, 64Cu-DOTA-h173 could be potentially used as a probe for noninvasive imaging of Axl expression, which could collect important information regarding tumor response to Axl-targeted therapeutic interventions.
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影响因子：
2.4
作者：
Song H;Sgouros G
通讯作者：
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影响因子：
3.1
作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0909333107
发表时间：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.1
作者：
Liu, Shuanglong;Li, Dan;Conti, Peter S.
通讯作者：
Conti, Peter S.