Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases
Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases
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DOI：
10.1073/pnas.97.3.1206
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发表时间：
2000-02-01
影响因子：
11.1
通讯作者：
Hoffman, RM
中科院分区：
文献类型：
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作者：
Yang, M;Baranov, E;Hoffman, RM
我们已经成像，在真实的时间，荧光肿瘤生长和转移的活小鼠。全身光学成像系统是外部和非侵入性的。它提供了前所未有的连续视觉监测恶性肿瘤的生长和蔓延的完整的动物。我们已经建立了新的人类和啮齿动物肿瘤，稳定表达非常高水平的维多利亚水母绿色荧光蛋白（GFP），并将这些移植到适当的动物。将B16 F0-GFP小鼠黑素瘤细胞注射到6周龄C57 BL/6和裸鼠的尾静脉或门静脉中。全身光学图像显示B16 F0-GFP在脑、肝和骨中的转移性病变，其用于真实的时间，定量测量这些器官中的每一个中的肿瘤生长。将AC 3488-GFP人结肠癌原位手术植入裸鼠中。全身光学图像显示，在真实的时间，生长的原发性结肠肿瘤及其转移病灶的肝脏和骨骼。成像是用透射照明落射荧光显微镜或荧光灯箱和热电冷却彩色电荷耦合器件相机。转移瘤和微转移瘤的成像深度取决于其大小。直径为60 μ m的肿瘤在0.5 mm的深度可检测到，而直径为1，800 μ m的肿瘤在2.2 mm的深度可观察到。通过强大的GFP荧光，可以对生长中的肿瘤进行简单，非侵入性和高度选择性的成像，从而能够对肿瘤生长和转移形成进行详细成像。这将有助于研究癌症生长的调节剂，包括潜在的化疗药物的抑制作用。
We have imaged, in real time, fluorescent tumors growing and metastasizing in live mice. The whole-body optical imaging system is external and noninvasive. It affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals. We have established new human and rodent tumors that stably express very high levels of the Aequorea victoria green fluorescent protein (GFP) and transplanted these to appropriate animals. B16F0-GFP mouse melanoma cells were injected into the tail vein or portal vein of 6-week-old C57BL/6 and nude mice. Whole-body optical images showed metastatic lesions in the brain, liver, and bone of B16F0-GFP that were used for real time, quantitative measurement of tumor growth in each of these organs. The AC3488-GFP human colon cancer was surgically implanted orthotopically into nude mice. Whole-body optical images showed, in real time, growth of the primary colon tumor and its metastatic lesions in the liver and skeleton. Imaging was with either a trans-illuminated epifluorescence microscope or a fluorescence light box and thermoelectrically cooled color charge-coupled device camera. The depth to which metastasis and micrometastasis could be imaged depended on their size. A 60-mu m diameter tumor was detectable at a depth of 0.5 mm whereas a 1,800-mu m tumor could be visualized at 2.2-mm depth. The simple, noninvasive, and highly selective imaging of growing tumors, made possible by strong GFP fluorescence, enables the detailed imaging of tumor growth and metastasis formation. This should facilitate studies of modulators of cancer growth including inhibition by potential chemotherapeutic agents.