Identification of a sodium pump Na+/K+ ATPase α1-targeted peptide for PET imaging of breast cancer
Identification of a sodium pump Na+/K+ ATPase α1-targeted peptide for PET imaging of breast cancer
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鉴定用于乳腺癌 PET 成像的钠泵 Na( )/K( ) ATPase α1 靶向肽。
DOI：
10.1016/j.jconrel.2018.05.019
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发表时间：
2018-07-10
影响因子：
10.8
通讯作者：
Zeng, Mu-Sheng
中科院分区：
文献类型：
--
作者：
Wang, Qian;Li, Shi-Bing;Zeng, Mu-Sheng
钠泵Na+/K+ ATP酶a1亚基（NKA a1）是一种具有吸引力的癌症相关生物标志物和治疗靶点，与包括乳腺癌在内的多种癌症的发生和发展密切相关。目前，NKA α 1抑制剂UNBS 1450已经证明了其在个性化癌症治疗中的巨大治疗潜力。NKA α 1表达的非侵入性成像能力将有助于选择可能受益于该药物的癌症患者。在这里，我们通过噬菌体展示鉴定了特异性归巢于乳腺癌的S3肽。体内外实验结果表明，S3肽具有良好的靶向性。由于S3噬菌体的结合活性与各种乳腺癌细胞中NKA α 1的表达水平正相关，因此NKA α 1被验证为S3肽的主要靶标。基于107例乳腺癌患者的免疫组化染色结果，证实NKA α 1是一种新的乳腺癌追踪标记物和预后预测因子。重要的是，我们提出并验证了一种基于S3肽的放射性示踪剂F-18-ALF-NOTA-S3，用于小鼠模型中乳腺癌和其他NKA α 1过表达癌症（包括肝细胞癌和非小细胞肺癌）的PET（正电子发射断层扫描）成像。我们的研究结果表明，F-18-ALF-NOTA-S3在NKA α 1阳性病变的可视化中具有潜在的应用价值，这为表征肿瘤表型成像提供了一种新的方法。
The sodium pump Na+/K+ ATPase a1 subunit(NKA a1), an attractive cancer-related biomarker and therapeutic target, is closely related to the development and progression of several cancers including breast cancer. Currently, a NKA a1 inhibitor, UNBS1450, has already evidenced its great therapeutic potential in personalized cancer treatment. The ability of non-invasive imaging of NKA a1 expression would be useful for selecting cancer patients who may benefit from this drug. Here, we identified an S3 peptide that is specifically homed to breast cancer by phage display. All data of in vitro and in vivo experiments suggested the excellent targeting character of the S3 peptide. As the binding activity of the S3 phage was positively correlated to the level of NKA a1 expression in various breast cancer cells, NKA a1 was validated as the primary target of the S3 peptide. Based on immunohistochemistry staining result of 107 breast cancer patients, NKA a1 was verified to be a novel tracking marker and a prognostic predictor for breast cancer. Importantly, we proposed and validated an S3 peptidebased radiotracer F-18-ALF-NOTA-S3 for PET (Positron Emission Tomography) imaging of breast cancer and other NKA a1-overexpressing cancers, including hepatocellular carcinoma and non-small cell lung cancer, in mouse models. Our findings demonstrated the potential application of F-18-ALF-NOTA-S3 for visualization of NKA a1-positive lesions, which provide a new approach to character tumor phenotypic imaging.