Kishimoto Hiroyuki, Kojima Toru, Watanabe Yuichi, Kagawa Shunsuke, Fujiwara Toshiya, Uno Futoshi, Teraishi Fuminori, Kyo Satoru, Mizuguchi Hiroyuki, Hashimoto Yuuri, Urata Yasuo, Tanaka Noriaki, Fujiwara Toshiyoshi
Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Nat Med. 2006 Oct;12(10):1213-9. doi: 10.1038/nm1404. Epub 2006 Oct 1.
Currently available methods for detection of tumors in vivo such as computed tomography and magnetic resonance imaging are not specific for tumors. Here we describe a new approach for visualizing tumors whose fluorescence can be detected using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401). OBP-401 contains the replication cassette, in which the human telomerase reverse transcriptase (hTERT) promoter drives expression of E1 genes, and the GFP gene for monitoring viral replication. When OBP-401 was intratumorally injected into HT29 tumors orthotopically implanted into the rectum in BALB/c nu/nu mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. Our results indicate that OBP-401 causes viral spread into the regional lymphatic area and selectively replicates in neoplastic lesions, resulting in GFP expression in metastatic lymph nodes. This technology is adaptable to detect lymph node metastasis in vivo as a preclinical model of surgical navigation.
目前用于体内肿瘤检测的方法，如计算机断层扫描和磁共振成像，对肿瘤并不具有特异性。在此，我们描述了一种可视化肿瘤的新方法，其荧光可通过表达绿色荧光蛋白（GFP）的端粒酶特异性复制型腺病毒（OBP - 401）进行检测。OBP - 401包含复制盒，其中人端粒酶逆转录酶（hTERT）启动子驱动E1基因的表达，以及用于监测病毒复制的GFP基因。当将OBP - 401瘤内注射到原位植入BALB/c nu/nu小鼠直肠的HT29肿瘤中时，在开腹手术中使用三芯片彩色冷却电荷耦合器件相机可观察到腹主动脉旁淋巴结转移。我们的结果表明，OBP - 401导致病毒扩散到区域淋巴区域并在肿瘤病变中选择性复制，从而导致转移淋巴结中GFP表达。作为手术导航的临床前模型，该技术适用于体内检测淋巴结转移。
