Adusumilli P S, Eisenberg D P, Stiles B M, Hendershott K J, Stanziale S F, Chan M-K, Hezel M, Huq R, Rusch V W, Fong Y
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Surg Endosc. 2006 Apr;20(4):628-35. doi: 10.1007/s00464-005-0259-6. Epub 2006 Jan 30.
Replication-competent, tumor specific herpes simplex virus NV1066 expresses green fluorescent protein (GFP) in infected cancer cells. We sought to determine the feasibility of GFP-guided imaging technology in the intraoperative detection of small tumor nodules.
Human cancer cell lines were infected with NV1066 at multiplicities of infection of 0.01, 0.1 and 1. Cancer cell specific infectivity, vector spread and GFP signal intensity were measured by flow cytometry and time-lapse digital imaging (in vitro); and by use of a stereomicroscope and endoscope equipped with a fluorescent filter (in vivo).
NV1066 infected all cancer cell lines and expressed GFP at all MOIs. GFP signal was significantly higher than the autofluorescence of normal cells. One single dose of NV1066 spread within and across body cavities and selectively infected tumor nodules sparing normal tissue. Tumor nodules undetectable by conventional thoracoscopy and laparoscopy were identified by GFP fluorescence.
Virally-directed fluorescent imaging (VFI) is a real-time novel molecular imaging technology that has the potential to enhance the intraoperative detection of endoluminal or endocavitary tumor nodules.
具有复制能力的肿瘤特异性单纯疱疹病毒NV1066在受感染的癌细胞中表达绿色荧光蛋白（GFP）。我们试图确定GFP引导成像技术在术中检测小肿瘤结节的可行性。
用感染复数为0.01、0.1和1的NV1066感染人癌细胞系。通过流式细胞术和延时数字成像（体外）；以及使用配备荧光滤光片的立体显微镜和内窥镜（体内）测量癌细胞特异性感染性、载体传播和GFP信号强度。
NV1066感染了所有癌细胞系，并在所有感染复数下表达GFP。GFP信号明显高于正常细胞的自发荧光。单剂量的NV1066在体腔内和跨体腔扩散，并选择性地感染肿瘤结节，而不损伤正常组织。通过GFP荧光可识别传统胸腔镜和腹腔镜检查无法检测到的肿瘤结节。
病毒导向荧光成像（VFI）是一种实时新型分子成像技术，有可能增强术中对腔内或腔内肿瘤结节的检测。
