Real-time diagnostic imaging of tumors and metastases by use of a replication-competent herpes vector to facilitate minimally invasive oncological surgery
Real-time diagnostic imaging of tumors and metastases by use of a replication-competent herpes vector to facilitate minimally invasive oncological surgery
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DOI：
10.1096/fj.05-5316fje
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发表时间：
2006-02-01
期刊：
影响因子：
4.8
通讯作者：
Fong, Yuman
中科院分区：
文献类型：
--
作者：
Adusumilli, Prasad S.;Stiles, Brendon M.;Fong, Yuman
目前将微创技术扩展到肿瘤手术领域的努力受到缺乏肿瘤边缘的准确可视化和未能真实的实时检测微转移的阻碍。我们使用了一种具有癌症选择性感染和复制的疱疹病毒载体的全身递送来精确区分正常和恶性组织。NV 1066是一种遗传修饰的、具有复制能力的单纯疱疹病毒，携带增强型绿色荧光蛋白（GFP）的转基因。我们测试了NV1066在体外和体内广泛的癌症中描绘肿瘤组织的潜力，以及NV1066诱导的GFP表达是否可以使用具有荧光过滤器的手术内窥镜在体内模型中检测小的肿瘤灶和转移灶。我们的研究结果表明，NV1066可用于实时术中成像和早期癌症和转移的增强检测。我们证明，单剂量的NV1066，无论是局部（肿瘤内或腔内）或全身给药，将检测局部区域和远处疾病整个身体。这种癌症选择性在来自16种不同主要器官的110种癌细胞中得到证实。辅助微创内窥镜检查发现了传统腹腔镜/胸腔镜无法识别的显微肿瘤沉积物。此外，NV1066转运和感染肿瘤和转移的能力在不同动物模型（免疫活性和免疫缺陷）的同系和移植肿瘤中得到证实。通过组织学、免疫组织化学和qRT-PCR证实癌症选择性GFP表达。这些研究为通过微创内窥镜技术对肿瘤和转移瘤进行实时术中诊断成像奠定了基础。
Current efforts on expanding minimally invasive techniques into the realm of oncological surgery are hindered by lack of accurate visualization of tumor margins and failure to detect micro metastases in real time. We used a systemic delivery of a herpes viral vector with cancer-selective infection and replication to precisely differentiate between normal and malignant tissue. NV1066 is a genetically modified, replication-competent herpes simplex virus carrying a transgene for enhanced green fluorescent protein (GFP). We tested the potential of NV1066 in delineating tumor tissue in vitro and in vivo in a wide range of cancers and whether NV1066-induced GFP expression can detect small foci of tumors and metastases in in vivo models using an operating endoscope with fluorescent filters. Our findings indicate that NV1066 can be used for real-time intraoperative imaging and enhanced detection of early cancers and metastases. We demonstrate that a single dose of NV1066, administered either locally (intratumoral or intracavitary) or systemically, will detect loco-regional and distant disease throughout the body. Such cancer selectivity is confirmed in 110 types of cancer cells from 16 different primary organs. Fluorescence-aided minimally invasive endoscopy revealed microscopic tumor deposits unrecognized by conventional laparoscopy/ thoracoscopy. Furthermore, NV1066 ability to transit and infect tumor and metastases is proven in syngenic and transplanted tumors in different animal models, both immunocompetent and immunodeficient. Cancer-selective GFP expression is confirmed by histology, immunohistochemistry, and qRT-PCR. These studies form the basis for real-time, intraoperative diagnostic imaging of tumor and metastases by minimally invasive endoscopic technology.