School of Pharmacy, Institute for Drug Research, Faculty of Medicine, the Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Int J Mol Sci. 2013 Jul 12;14(7):14669-88. doi: 10.3390/ijms140714669.
In this study, we present the applicability of imaging epidermal growth factor (EGF) receptor levels in preclinical models of COLO205 carcinoma cells in vitro, mice with orthotopic tumors and ex vivo colorectal tumor biopsies, using EGF-labeled with IRDye800CW (EGF-NIR). The near infrared (NIR) bio-imaging of COLO205 cultures indicated specific and selective binding, reflecting EGF receptors levels. In vivo imaging of tumors in mice showed that the highest signal/background ratio between tumor and adjacent tissue was achieved 48 hours post-injection. Dissected colorectal cancer tissues from different patients demonstrated ex vivo specific imaging using the NIR bio-imaging platform of the heterogeneous distributed EGF receptors. Moreover, in the adjacent gastrointestinal tissue of the same patients, which by Western blotting was demonstrated as EGF receptor negative, no labeling with EGF-NIR probe was detected. Present results support the concept of tumor imaging by measuring EGF receptor levels using EGF-NIR probe. This platform is advantageous for EGF receptor bio-imaging of the NCI-60 recommended panel of tumor cell lines including 6-9 colorectal cell lines, since it avoids radioactive probes and is appropriate for use in the clinical setting using NIR technologies in a real-time manner.
在这项研究中,我们展示了使用表皮生长因子(EGF)标记的近红外染料 800CW(EGF-NIR),在体外 COLO205 癌细胞的临床前模型、荷瘤小鼠和离体结直肠肿瘤活检中,研究 EGF 受体水平在 COLO205 培养物中的近红外(NIR)生物成像表明具有特异性和选择性结合,反映了 EGF 受体水平。在荷瘤小鼠的体内成像中,在注射后 48 小时获得了肿瘤与相邻组织之间最高的信号/背景比。使用 NIR 生物成像平台对来自不同患者的离体结直肠组织进行了特异性成像,该平台显示出异质分布的 EGF 受体。此外,在同一患者的胃肠道相邻组织中,Western blot 证实 EGF 受体阴性,未检测到 EGF-NIR 探针的标记。目前的结果支持通过使用 EGF-NIR 探针测量 EGF 受体水平进行肿瘤成像的概念。该平台有利于 NCI-60 推荐的肿瘤细胞系panel 的 EGF 受体生物成像,包括 6-9 个结直肠细胞系,因为它避免了放射性探针,并且适合在临床环境中使用 NIR 技术实时进行。