Immunotargeting of Integrin α6β4 for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model.
Immunotargeting of Integrin α6β4 for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model.
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DOI：
10.1177/1536012115624917
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发表时间：
2016
影响因子：
2.8
通讯作者：
Saga T
中科院分区：
文献类型：
--
作者：
Aung W;Tsuji AB;Sudo H;Sugyo A;Furukawa T;Ukai Y;Kurosawa Y;Saga T
为了探索适合胰腺癌早期和特异性检测的成像探针，我们证明 α6β4 整合素是一个很好的靶标，并采用单光子发射计算机断层扫描 (SPECT) 或近红外 (NIR) 成像进行免疫靶向。通过蛋白质印迹和流式细胞术检查某些人胰腺癌细胞系中 α6β4 的表达水平。人类细胞系 BxPC-3 用于 α6β4 阳性，小鼠细胞系 A4 用于阴性对应物。我们用 Indium-111 (111In) 或吲哚菁绿 (ICG) 标记针对 α6β4 的抗体。将 111In 标记探针注射到荷瘤小鼠后，进行生物分布、SPECT、放射自显影 (ARG) 和免疫组织化学 (IHC) 研究。施用ICG标记的探针后，对肿瘤进行体内和离体近红外成像和荧光显微镜检查。与 A4 肿瘤相比，BxPC-3 肿瘤在 SPECT 中显示出更高的放射性配体结合，在 NIR 成像中显示出更高的荧光强度以及探针冲洗的延迟。 111In 标记探针、ARG 和 IHC 的生物分布图证实了探针的 α6β4 特异性结合。在这里，我们提出α6β4是诊断胰腺癌的理想靶标，并且可以使用放射性标记或ICG标记的α6β4抗体通过放射性核素成像和NIR成像来检测它。
To explore suitable imaging probes for early and specific detection of pancreatic cancer, we demonstrated that α6β4 integrin is a good target and employed single-photon emission computed tomography (SPECT) or near-infrared (NIR) imaging for immunotargeting. Expression levels of α6β4 were examined by Western blotting and flow cytometry in certain human pancreatic cancer cell lines. The human cell line BxPC-3 was used for α6β4-positive and a mouse cell line, A4, was used for negative counterpart. We labeled antibody against α6β4 with Indium-111 (111In) or indocyanine green (ICG). After injection of 111In-labeled probe to tumor-bearing mice, biodistribution, SPECT, autoradiography (ARG), and immunohistochemical (IHC) studies were conducted. After administration of ICG-labeled probe, in vivo and ex vivo NIR imaging and fluorescence microscopy of tumors were performed. BxPC-3 tumor showed a higher radioligand binding in SPECT and higher fluorescence intensity as well as a delay in the probe washout in NIR imaging when compared to A4 tumor. The biodistribution profile of 111In-labeled probe, ARG, and IHC confirmed the α6β4 specific binding of the probe. Here, we propose that α6β4 is a desirable target for the diagnosis of pancreatic cancer and that it could be detected by radionuclide imaging and NIR imaging using a radiolabeled or ICG-labeled α6β4 antibody.