Wu Chia-Che, Lin Erh-Hsuan, Lee Yu-Ching, Tai Cheng-Jeng, Kuo Tsu-Hsiang, Wang Hsin-Ell, Luo Tsai-Yueh, Fu Ying-Kai, Chen Haw-Jan, Sun Ming-Ding, Wu Chih-Hsiung, Wu Cheng-Wen, Leu Sy-Jye, Deng Win-Ping
Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 11031, Taiwan.
J Biomed Biotechnol. 2010;2010:167045. doi: 10.1155/2010/167045. Epub 2010 Dec 5.
A 12-mer amino acid peptide SATTHYRLQAAN, denominated TK4, was isolated from a phage-display library with fibrosarcoma tumor-binding activity. In vivo biodistribution analysis of TK4-displaying phage showed a significant increased phage titer in implanted tumor up to 10-fold in comparison with normal tissues after systemic administration in mouse. Competition assay confirmed that the binding of TK4-phage to tumor cells depends on the TK4 peptide. Intravenous injection of (131)I-labeled synthetic TK4 peptide in mice showed a tumor retention of 3.3% and 2.7% ID/g at 1- and 4-hour postinjection, respectively. Tumor-to-muscle ratio was 1.1, 5.7, and 3.2 at 1-, 4-, and 24-hour, respectively, and tumors were imaged on a digital γ-camera at 4-hour postinjection. The present data suggest that TK4 holds promise as a lead structure for tumor targeting, and it could be further applied in the development of diagnostic or therapeutic agent.
从具有纤维肉瘤肿瘤结合活性的噬菌体展示文库中分离出一种名为TK4的12氨基酸肽SATTHYRLQAAN。对展示TK4的噬菌体进行的体内生物分布分析表明，在小鼠全身给药后，植入肿瘤中的噬菌体滴度与正常组织相比显著增加，高达10倍。竞争试验证实，TK4噬菌体与肿瘤细胞的结合取决于TK4肽。在小鼠中静脉注射（131）I标记的合成TK4肽，在注射后1小时和4小时的肿瘤摄取率分别为3.3%和2.7% ID/g。肿瘤与肌肉的比值在1小时、4小时和24小时分别为1.1、5.7和3.2，并且在注射后4小时用数字γ相机对肿瘤进行成像。目前的数据表明，TK4有望作为肿瘤靶向的先导结构，并且它可以进一步应用于诊断或治疗剂的开发。
