國家衛生研究院 NHRI:Item 3990099045/3078
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    题名: Human breast tumor cells express multimodal imaging reporter genes
    作者: Lin, KM;Hsu, CH;Chang, WSW;Chen, CT;Lee, TW;Chen, CT
    贡献者: Division of Biotechnology and Pharmaceutical Research;Division of Medical Engineering Research
    摘要: Objective: Human ZR75-1 cells were among the first few characterized estrogen-dependent mammary gland carcinoma cell lines and had been utilized in various studies for the pro- or antitumor effect of xenoestrogens and antiestrogens. The objective of this study was to establish a breast tumor model in ZR75-1 cells bearing multimodal reporter genes to allow noninvasive imaging of tumor growth using fluorescence and nuclear imaging platforms. Methods and Results: Enhanced green fluorescent protein (eGFP) cDNA was fused at the C-terminus with herpes simplex virus type 1 thymidine kinase (HSV1-tk) to form the fusion reporter gene (eGFP-tk). In vitro proliferation, migration, and invasion assays revealed that eGFP-tk-transfected ZR75-1 cells exhibited decreased proliferation rate, migratory activity, and invasion ability compared to the wild-type cells. The functional HSV1-tk enzymatic activity in stably transfected cells were confirmed by in vitro ganciclovir (GCV) sensitivity and [I-123]2-fluoro-2-deoxy-1-beta-d-arabinofuranosyl-5-iodouracil (FIAU) accumulation assays. In vivo fluorescence and nuclear imaging were performed on nude mice bearing multiple subcutaneous xenografts established from ZR75-1-eGFP-tk and wild-type cells. Optical imaging was able to detect the green fluorescence of eGFP-tk tumor. The eGFP-tk reporter gene-specific imaging was achieved by single photon emission computed tomography (SPECT) using [I-123]FIAU as a radiotracer and demonstrated decreased FIAU uptake in eGFP-tk tumor by GCV treatment. Probably due to a flare reaction after GCV treatment, micro-positron emission tomography (micro-PET) imaging using 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) could not demonstrate decreases in FDG uptake. However, in vitro metabolic assay also revealed that eGFP-tk cells transiently increased [H-3]-deoxyglucose uptake in response to GCV treatment. Conclusions: This study confirmed the usefulness of eGFP-tk in many applications by providing, in vitro and in vivo, the sensitive and reporter gene-specific imaging. ZR75-1-eGFP-tk cells that are ready to incorporate in various imaging platforms constitute a useful model in breast cancer research.
    关键词: Radiology, Nuclear Medicine & Medical Imaging
    日期: 2008-09
    關聯: Molecular Imaging and Biology. 2008 Sep;10(5):253-263.
    Link to: http://dx.doi.org/10.1007/s11307-008-0147-2
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1536-1632&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000258247000004
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=49149111626
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