Departments of Radiology, Biomedical Engineering, and Pathology, NFCR Center for Molecular Imaging at Case, Case Western Reserve University, Wearn Building, Room B-42, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
Mol Cancer Ther. 2012 Oct;11(10):2202-11. doi: 10.1158/1535-7163.MCT-12-0211. Epub 2012 Jul 17.
We have developed a near-infrared (NIR) probe that targets cells overexpressing the EGF receptor (EGFR) for imaging glioblastoma brain tumors in live subjects. A peptide specific for the EGFR was modified with various lengths of monodiscrete polyethylene glycol (PEG) units and a NIR Cy5.5 fluorescence dye. The lead compound, compound 2, with one unit of PEG displayed good binding (8.9 μmol/L) and cellular uptake in glioblastoma cells overexpressing EGFR in vitro. The in vivo studies have shown that the probe was able to selectively label glioblastoma-derived orthotopic brain tumors. In vivo image analyses of peptide binding to the tumors using fluorescence-mediated molecular tomography revealed that the compound could distinguish between tumors expressing different levels of EGFR. The data presented here represent the first demonstration of differential quantitation of tumors expressing EGFR in live animals by a targeted NIR fluorescence probe using a molecular imaging device.
我们开发了一种近红外（NIR）探针，该探针针对过度表达表皮生长因子受体（EGFR）的细胞，用于活体对象中脑胶质瘤肿瘤的成像。一种针对 EGFR 的肽经过各种长度的单离散聚乙二醇（PEG）单元和 NIR Cy5.5 荧光染料的修饰。具有一个 PEG 单元的先导化合物 2 在体外过表达 EGFR 的脑胶质瘤细胞中表现出良好的结合（8.9 μmol/L）和细胞摄取。体内研究表明，该探针能够选择性标记脑胶质瘤来源的原位脑肿瘤。使用荧光介导的分子断层扫描对肽与肿瘤的结合进行的体内图像分析表明，该化合物能够区分表达不同水平 EGFR 的肿瘤。这里呈现的数据代表了使用分子成像设备的靶向 NIR 荧光探针首次在活体动物中对表达 EGFR 的肿瘤进行差异定量的证明。
