Small Animal Bioluminescence and Fluorescence Imaging System (with 3D capability)

描述（由申请人提供）：我们建议购买商业生物发光成像（BLI）系统，特别是卡尺（Xenogen）IVIS SpectrumTM。它将主要为六个NIH资助的研究团队提供服务，以开展生物医学研究。此外，通过小动物成像研究计划（U24- SAIRP），它将支持其他12项当前的研究调查，并作为新研究的催化剂。人们普遍认识到，成像增强了生物医学研究，特别是在肿瘤学。肿瘤表现出显著的异质性，因此，每个肿瘤作为其自身的对照是有利的。个体肿瘤的纵向研究有三个主要好处：i）需要更少的动物，ii）作为必然结果，需要更少的试剂（因此，可以更有效地筛选稀有和昂贵的药物和抗体），iii）更可靠的统计数据。生物发光成像对于在裸鼠中生长的小体积（包括亚可触知的）肿瘤的高通量筛选特别有效。可以观察整个小鼠，并且容易评估远端转移的发展，而无需关于位置的先验假设（与有效病理学的要求相反）。BLI确实需要引入报告基因（通常是萤火虫荧光素酶），但这是可靠完成的，并且在UT西南医学中心是常规的。BLI具有特异性启动子（例如，缺氧、丛生蛋白、雌激素或其它应激元件）可被包括以调节荧光素酶表达。这也可以使用荧光报告子来实现，并且Spectrum还可以进行荧光成像，光谱解混以可靠地去除自发荧光或区分具有不同波长的报告子。Spectrum为生物发光和荧光成像提供了三维功能，这大大增强了区分肿瘤发展位置的能力。尽管如此，我们还是提供了一个使用自制仪器的BLI服务，但我们相信使用标准商业平台添加功能是很重要的。商业系统更加用户友好，允许不同的调查人员迅速接受培训，进行成像研究。此外，UT Southwestern正在建立一个无特定病原体（SPF）设施，包括一个需要成像能力的小动物肿瘤模型核心资源。虽然BLI仪器相对便宜，但它们超出了个人研究人员的范围，这种共享仪器将在有效使用的同时促进新的实验。 BLI已成为小肿瘤体积和转移性扩散的首选筛查工具。新仪器将加速我们机构新疗法的开发，这些新疗法将直接转化为临床，从而为患者提供更有效的未来治疗。虽然报告基因仅在临床前环境中相关，但所获得的结果应提供对优化患者治疗方案的见解。

DESCRIPTION (provided by applicant): We propose to purchase a commercial bioluminescent imaging (BLI) system, specifically, the Caliper (Xenogen) IVIS SpectrumTM. It will primarily serve six NIH-funded research teams to undertake biomedical research. In addition, through a Small Animal Imaging Research Program (U24- SAIRP) it will support 12 other current research investigations and serve as a catalyst for new research. It is widely recognized that imaging enhances biomedical research, particularly in oncology. Tumors exhibit substantial heterogeneity, and thus, it is advantageous for each tumor to serve as its own control. Longitudinal studies in individual tumors enjoy three primary benefits: i) the need for fewer animals, ii) as a corollary, the need for less reagent (therefore, rare and costly drugs and antibodies can be screened more efficiently), iii) more robust statistics. Bioluminescent imaging is particularly effective for high throughput screening of tumors at small volumes (including sub palpable) growing in nude mice. Whole mice may be observed and the development of remote metastasis is readily assessed without a priori assumptions about location (in contrast to the requirements for effective pathology). BLI does require introduction of a reporter gene (typically, firefly luciferase), but this is reliably accomplished and is routine at UT Southwestern Medical Center. BLI has the additional advantage that specific promoters (e.g., hypoxia, clusterin, estrogen, or other stress elements) may be included to regulate luciferase expression. This can also be achieved using fluorescent reporters and the Spectrum can also undertake fluorescent imaging, with spectral unmixing to reliably remove autofluorescence or differentiate reporters with distinct wavelengths. The Spectrum offers 3-dimensional capabilities for both bioluminescent and fluorescence imaging, which greatly enhances the ability to distinguish the location of developing tumors. Hitherto, we provided a BLI service using home built instrumentation, but we believe it is important to add a capability using a standard commercial platform. Commercial systems are more user friendly allowing diverse investigators to be rapidly trained to conduct imaging studies. Furthermore, UT Southwestern is establishing a specific pathogen free (SPF) facility including a small animal tumor model core resource, which requires imaging capabilities. While BLI instruments are relatively cheap, they are beyond the scope of individual investigators, and this shared instrument will facilitate new experiments while being efficiently used. BLI has become established as the premiere screening tool for small tumor volumes and metastatic spread. The new instrument will accelerate development of new therapies in our institution, which will be directly translatable to the clinic, and thus, provide more effective future therapy for patients. While the reporter gene is only relevant in the preclinical setting, the results achieved should provide insight into optimizing therapy protocols for patients.