首页> 外文期刊>Neurosurgery >Noninvasive bioluminescence imaging of luciferase expressing intracranial U87 xenografts: correlation with magnetic resonance imaging determined tumor volume and longitudinal use in assessing tumor growth and antiangiogenic treatment effect.
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Noninvasive bioluminescence imaging of luciferase expressing intracranial U87 xenografts: correlation with magnetic resonance imaging determined tumor volume and longitudinal use in assessing tumor growth and antiangiogenic treatment effect.

机译:荧光素酶表达颅内U87异种移植物的非侵入性生物发光成像:与磁共振成像的相关性确定了肿瘤的大小和纵向用于评估肿瘤的生长和抗血管生成治疗的效果。

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OBJECTIVE: Outcome studies in rodent tumor models rely on both histological and noninvasive study end points. Intracranial models require special tools to observe tumor growth over time noninvasively, such as magnetic resonance imaging (MRI), computed tomographic scanning, or cranial window techniques. These techniques share disadvantages in terms of cost, technical expertise required, and overall animal throughput for analysis. In this report, we sought to validate the use of the relatively newer technique of bioluminescence imaging (BLI) of intracranial glioblastoma xenograft growth by comparing it with gadolinium-enhanced MRI. METHODS: U87MG glioma cell lines genetically engineered to express the firefly luciferase gene were stereotactically injected into nude mice in the left frontal lobe. Weekly BLI and MRI were performed after the inoculation of tumor cells. For BLI, tumor growth was assessed as the peak BLI after systemic injection of luciferin substrate. MRI-based growth curves were created by three-dimensional volumetric reconstruction of axial gadolinium-enhanced MRI data covering the whole brain. In a separate experiment, mice were treated with adenoviruses encoding antiangiogenic soluble vascular endothelial growth factor receptors, and treatment effect was monitored by BLI. RESULTS: Untreated tumor growth was readily detected and observed over time by serial BLI measurements. Furthermore, tumor-derived light emission was highly correlated with volume of tumor as assessed by MRI. Furthermore, the tested antiangiogenic treatment effect was readily detected using this technique, suggesting the power of the technique for sensitive monitoring of novel therapeutics. CONCLUSION: BLI offers a simple and rapid technique for assessing intracranial glioblastoma growth in rodent models noninvasively, which correlates well with MRI. The speed of the BLI technique can increase experimental throughput, allows for targeted histological analysis in animals showing the greatest treatment effects, and provides new insights into the kinetics of intracranial tumor growth in the setting of different treatments.
机译:目的:在啮齿动物肿瘤模型中的结果研究依赖于组织学和非侵入性研究终点。颅内模型需要特殊的工具来无创地观察肿瘤随时间的增长,例如磁共振成像(MRI),计算机断层扫描或颅窗技术。这些技术在成本,所需的技术专长以及用于分析的总体动物生产量方面均具有劣势。在本报告中,我们试图通过与with增强的MRI进行比较来验证使用较新的颅内胶质母细胞瘤异种移植物生长的生物发光成像(BLI)技术。方法:将经基因工程改造表达萤火虫荧光素酶基因的U87MG胶质瘤细胞系立体定向注入左额叶裸鼠。接种肿瘤细胞后每周进行BLI和MRI检查。对于BLI,肿瘤生长被评估为系统注射荧光素底物后的BLI峰值。基于MRI的生长曲线是通过三维volume轴增强MRI数据覆盖整个大脑的三维体积重建而创建的。在另一个实验中,用编码抗血管生成可溶性血管内皮生长因子受体的腺病毒治疗小鼠,并通过BLI监测治疗效果。结果:未经治疗的肿瘤生长很容易被检测到,并通过连续BLI测量随时间推移而观察到。此外,通过MRI评估,肿瘤来源的发光与肿瘤体积高度相关。此外,使用该技术很容易检测出所测试的抗血管生成治疗效果,表明该技术对新型疗法进行灵敏监测的能力。结论:BLI提供了一种简单,快速的技术,用于无创评估啮齿动物模型中颅内胶质母细胞瘤的生长,与MRI密切相关。 BLI技术的速度可以提高实验通量,可以在动物中进行有针对性的组织学分析,从而显示出最大的治疗效果,并且可以为不同治疗背景下颅内肿瘤生长的动力学提供新的见解。

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