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首页> 外文期刊>ACS Omega >Integrin α6-Targeted Positron Emission Tomography Imaging of Colorectal Cancer
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Integrin α6-Targeted Positron Emission Tomography Imaging of Colorectal Cancer

机译:大肠癌的整合素α6靶向正电子发射断层显像

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Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin α6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin α6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics. In this study, we developed a radiotracer, 18F-RWY, based on this integrin α6-targeted RWY peptide for positron emission tomography (PET) imaging of CRC. Integrin α6 was overexpressed on several CRC cells including HT29 cells where the biotin-labeled RWY peptide colocalized with integrin α6. 18F-RWY PET imaging was performed on subcutaneous, chemically induced, and genetically engineered CRC mice. 18F-RWY generated high PET signals in subcutaneous HT29 tumors, and the tumor uptake of 18F-RWY was reduced by a blocking study using nonradio-labeled RWY. Moreover, 18F-RWY PET imaging enabled detection of CRC in chemically induced and genetically engineered CRC mice. The overexpression of integrin α6 in tumor tissues isolated from chemically induced and genetically engineered CRC mice was confirmed. These results demonstrate the potential clinical application of 18F-RWY for PET imaging of CRC.
机译:大肠癌(CRC)是全球第三大常见癌症,也是导致癌症死亡的第四大主要原因。整联蛋白α6在CRC的所有阶段均过表达,这使其成为CRC的潜在诊断生物标志物。以前,我们使用噬菌体展示技术鉴定了整合素α6靶向肽CRWYDENAC(称为RWY),并将其用于鼻咽癌特异性纳米治疗。在这项研究中,我们基于这种整合素α6靶向的RWY肽开发了一种放射性示踪剂18F-RWY,用于CRC的正电子发射断层扫描(PET)成像。整联蛋白α6在包括HT29细胞在内的几种CRC细胞中过表达,其中生物素标记的RWY肽与整联蛋白α6共定位。在皮下,化学诱导和基因改造的CRC小鼠上进行18F-RWY PET成像。 18F-RWY在皮下HT29肿瘤中产生高PET信号,并且通过使用非放射性标记的RWY的阻断研究降低了18F-RWY的肿瘤摄取。此外,18F-RWY PET成像能够检测化学诱导和基因工程改造的CRC小鼠中的CRC。证实从化学诱导和基因工程的CRC小鼠分离的肿瘤组织中整合素α6的过表达。这些结果证明了18F-RWY在CRC的PET成像中的潜在临床应用。

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