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Abstract：
EGFRvIII is expressed only in tumor cells and strongly in glioblastoma and is considered a promising target in cancer diagnosis and therapy. Aptamers are synthetic single-stranded oligonucleotides that bind to biochemical target molecules with high binding affinity and specificity. This study examined the potential of the 68Ga-NOTA-EGFRvIII aptamer as a nuclear imaging probe for visualizing EGFRvIII-expressing glioblastoma by positron emission tomography (PET). EGFRvIII aptamer was selected using the SELEX technology, and flow cytometry and fluorescence microscopy verified the high binding affinity to EGFRvIII positive U87MG vIII 4.12 glioma cells but not to EGFRvIII negative U87MG cells. The EGFRvIII aptamer was conjugated with a chelator (1,4,7-triazanonane-1,4,7-triyl)triacetic acid (NOTA) for 68Ga-labeling. The 68Ga-NOTA-EGFRvIII aptamer was prepared using the preconcentration-based labeling method with a high radiolabeling yield at room temperature. Ex vivo biodistribution analyses confirmed the significantly higher tumor uptake of the 68Ga-NOTA-EGFRvIII aptamer in EGFRvIII-expressing xenograft tumors than that in EGFRvIII negative tumors, confirming the specific tumor uptake of the 68Ga-NOTA-EGFRvIII aptamer in vivo. PET imaging studies revealed a high retention rate of the 68Ga-NOTA-EGFRvIII aptamer in U87MG vIII 4.12 tumors but only low uptake levels in U87-MG tumors, suggesting that the 68Ga-NOTA-EGFRvIII aptamer may be used as a PET imaging agent for EGFRvIII-expressing glioblastoma.
摘要：
EGFRvIII仅在肿瘤细胞中表达，在胶质母细胞瘤中强烈表达，被认为是癌症诊断和治疗中的有希望的靶标。适体是以高结合亲和力和特异性结合生化靶分子的合成单链寡核苷酸。这项研究检查了68Ga-NOTA-EGFRvIII适体作为核成像探针的潜力，用于通过正电子发射断层扫描（PET）可视化表达EGFRvIII的胶质母细胞瘤。使用SELEX技术选择EGFRvIII适体，流式细胞术和荧光显微镜验证了对EGFRvIII阳性U87MGvIII4.12胶质瘤细胞的高结合亲和力，但对EGFRvIII阴性U87MG细胞没有。EGFRvIII适体与螯合剂(1,4,7-三氮杂壬烷-1,4,7-三基)三乙酸(NOTA)缀合,用于68Ga标记。68Ga-NOTA-EGFRvIII适体使用基于预浓缩的标记方法在室温下以高放射性标记产率制备。离体生物分布分析证实，在表达EGFRvIII的异种移植肿瘤中，68Ga-NOTA-EGFRvIII适体的肿瘤摄取明显高于EGFRvIII阴性肿瘤，确认68Ga-NOTA-EGFRvIII适体在体内的特异性肿瘤摄取。PET成像研究显示68Ga-NOTA-EGFRvIII适体在U87MGvIII4.12肿瘤中的高保留率，但在U87-MG肿瘤中仅低摄取水平。提示68Ga-NOTA-EGFRvIII适体可用作表达EGFRvIII的胶质母细胞瘤的PET显像剂。
