In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus
In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus
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DOI：
10.1038/nm1404
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发表时间：
2006-10-01
期刊：
影响因子：
82.9
通讯作者：
Fujiwara, Toshiyoshi
中科院分区：
文献类型：
--
作者：
Kishimoto, Hiroyuki;Kojima, Toru;Fujiwara, Toshiyoshi
目前可用的体内肿瘤检测方法，如计算机断层扫描和磁共振成像，对肿瘤没有特异性。在这里，我们描述了一种新的方法，可视化肿瘤的荧光可以检测到使用端粒酶特异性复制能力腺病毒表达绿色荧光蛋白（GFP）（OBP-401）。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小鼠直肠中的HT 29肿瘤中时，在三芯片彩色冷却电荷耦合器件照相机下，可以在剖腹手术时观察到主动脉旁淋巴结转移。我们的研究结果表明，OBP-401导致病毒扩散到区域淋巴区，并选择性地在肿瘤病变中复制，导致转移性淋巴结中的GFP表达。该技术适用于检测体内淋巴结转移，作为手术导航的临床前模型。
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.