An optimized triple modality reporter for quantitative in vivo tumor imaging and therapy evaluation.

An optimized triple modality reporter for quantitative in vivo tumor imaging and therapy evaluation.
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DOI:
10.1371/journal.pone.0097415
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Tsien RY
Tsien RY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Levin RA;Felsen CN;Yang J;Lin JY;Whitney MA;Nguyen QT;Tsien RY

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我们提出了一种优化的三模报告结构,该报告结构结合了远红荧光蛋白(E2-Crimson)、增强型萤火虫荧光素酶(Luc2)和截短的野生型单纯疱疹病毒I型胸苷激酶(Wttk),允许通过荧光、生物发光和正电子发射断层扫描来敏感地、长期地跟踪体内肿瘤的生长。两个人癌细胞系(MDA-MB-231乳腺癌和HT-1080纤维肉瘤癌)成功地转导了该三种模式的报告基因。利用荧光和生物发光成像技术,在裸鼠体内准确定量了化疗药物单甲基金黄色E对MDA-MB-231肿瘤的治疗效果。荧光信号与生物发光信号呈正相关,且与体外肿瘤重量呈正相关。这是首次报道使用来自多模式报告结构的荧光和生物发光信号来测量体内的药物疗效。
We present an optimized triple modality reporter construct combining a far-red fluorescent protein (E2-Crimson), enhanced firefly luciferase enzyme (Luc2), and truncated wild type herpes simplex virus I thymidine kinase (wttk) that allows for sensitive, long-term tracking of tumor growth in vivo by fluorescence, bioluminescence, and positron emission tomography. Two human cancer cell lines (MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer) were successfully transduced to express this triple modality reporter. Fluorescence and bioluminescence imaging of the triple modality reporter were used to accurately quantify the therapeutic responses of MDA-MB-231 tumors to the chemotherapeutic agent monomethyl auristatin E in vivo in athymic nude mice. Positive correlation was observed between the fluorescence and bioluminescence signals, and these signals were also positively correlated with the ex vivo tumor weights. This is the first reported use of both fluorescence and bioluminescence signals from a multi-modality reporter construct to measure drug efficacy in vivo.
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