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首页> 美国卫生研究院文献>Scientific Reports >A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors
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A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors

机译：一种靶向CXCR4的新型近红外（NIR）荧光探针（肽R-NIR750）可特异性检测表达CXCR4的肿瘤

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C-X-C chemokine receptor 4 (CXCR4) is over-expressed in multiple human cancers and correlates with tumor aggressiveness, poor prognosis and increased risk for distant metastases. Imaging agents for CXCR4 are thus highly desirable. We developed a novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) conjugating the new developed CXCR4 peptidic antagonist Peptide R with the NIR fluorescent dye VivoTag-S750. Specific CXCR4 binding was obtained in cells overexpressing human CXCR4 (B16-hCXCR4 and human melanoma cells PES43), but not in CXCR4 low expressing cells (FB-1). Ex vivo evaluation demonstrated that PepR-NIR750 specifically detects B16-hCXCR4-derived subcutaneous tumors and lung metastases. Fluorescence Molecular Tomography (FMT) in vivo imaging was performed on mice carrying subcutaneous CHO and CHO-CXCR4 tumors. PepR-NIR750 accumulates only in CXCR4-positive expressing subcutaneous tumors. Additionally, an intense NIR fluorescence signal was detected in PES43-derived lung metastases of nude mice injected with PepR-NIR750 versus mice injected with VivoTag-S750. With a therapeutic intent, mice bearing PES43-derived lung metastases were treated with Peptide R. A the dramatic reduction in PES43-derived lung metastases was detected through a decrease of the PepR-NIR750 signal. PepR-NIR750 is a specific probe for non-invasive detection of human high CXCR4-expressing tumors and metastatic lesion and thus a valuable tool for cancer molecular imaging.
机译：C-X-C趋化因子受体4（CXCR4）在多种人类癌症中过表达，并且与肿瘤侵袭性，预后不良和远处转移的风险增加相关。因此，非常需要用于CXCR4的显像剂。我们开发了一种新型的靶向CXCR4的近红外（NIR）荧光探针（肽R-NIR750），将新开发的CXCR4肽拮抗剂肽R与NIR荧光染料VivoTag-S750结合在一起。在过表达人CXCR4的细胞（B16-hCXCR4和人黑素瘤细胞PES43）中获得了特异性CXCR4结合，但在低表达CXCR4的细胞（FB-1）中则没有。体外评估表明，PepR-NIR750可特异性检测源自B16-hCXCR4的皮下肿瘤和肺转移。在携带皮下CHO和CHO-CXCR4肿瘤的小鼠上进行了荧光分子层析成像（FMT）体内成像。 PepR-NIR750仅在表达CXCR4阳性的皮下肿瘤中蓄积。另外，与注射VivoTag-S750的小鼠相比，在注射PepR-NIR750的裸鼠的PES43衍生的肺转移中检测到强烈的NIR荧光信号。出于治疗目的，用肽R治疗携带PES43来源的肺转移的小鼠。通过减少PepR-NIR750信号检测到PES43来源的肺转移的急剧减少。 PepR-NIR750是用于无创检测人类高表达CXCR4的肿瘤和转移灶的特异性探针，因此是癌症分子成像的重要工具。

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