Fluorescence Imaging to Optimize Cancer Detection

描述（由申请人提供）：用于量化肿瘤受体活性的分子成像在成像细胞外蛋白信号方面具有不可思议的潜力，然而许多配体分子不能有效地使用，因为它们不能区分简单的基于血管通透性的摄取和真正的受体结合。在更新期间，允许肿瘤分子定量摄取的方法的发展是该资助的主要重点。利用一种为小动物定制的新型磁共振引导光学（MRgO）成像仪器，对体内受体活性进行荧光成像，主要用于胶质瘤肿瘤研究。硬件和软件子系统将进一步开发，在MR数据的引导下提供4层荧光断层扫描的体积数据，并叠加以实现整个原位肿瘤的可视化。这项工作的目的是分析胶质瘤肿瘤的分子示踪剂如何有效地用于量化肿瘤受体活性，以及对比MRI的血管灌注。小分子表皮生长因子（EGF）与非特异性荧光团剂一起用作探针，表明摄取的比例测量可以导致结合的EGF受体摄取的量化。胶质瘤肿瘤是微创的，因此不能用典型的磁共振成像检测到，可以用这种新的探针分子检测到，双探针方法将用于显示MRgO成像如何提供一种全新的方法来成像这种疾病。在系统中研究了不同分子量的高、低亲和探针的比例成像设计，并进行了离体验证，以确认体内图像真实反映组织浓度水平。该项目以研究微侵入和测试检测自发和在抗血管治疗的设置结束。该基金的重点是技术开发和方法开发，即如何将光学荧光有效地添加到成像科学中，以及这两种潜在的癌症应用。

DESCRIPTION (provided by applicant): Molecular imaging to quantify tumor receptor activity has incredible potential for imaging extracellular protein signaling, yet many ligand molecules cannot be used effectively, because they do not differentiate between simple vascular permeability based uptake and true receptor binding. The development of methodologies which allow quantitative uptake of molecules in tumors is a primary focus of this grant in the renewal period. Fluorescence imaging of receptor activity in vivo is done using a novel Magnetic Resonance-guided Optical (MRgO) imaging instrument that is customized for small animals, with a primary focus on glioma tumor studies. The hardware and software sub- systems will be developed further to provide 4 layer volumetric data of fluorescence tomography guided by the MR data, and overlayed for visualization of the entire orthotopic tumor. The goal of this work is to analyze how molecular tracers of glioma tumors can be used to effectively quantify tumor receptor activity, in addition to vascular perfusion from contrast MRI. The small molecule epidermal growth factor (EGF) is used as a probe in conjunction with a non-specific fluorophore agent to show that ratiometric measurements of the uptake could lead to quantification of the bound EGF Receptor uptake. Glioma tumors that are microinvasive and therefore are not detectable with typical MR imaging can be detected with this new probe molecule, and the dual probe method will be used to show how MRgO imaging can provide a fundamentally new method to image this disease. The design of high and low affinity probes of difference molecular weights for ratiometric imaging is studied in the system with ex vivo validation, to confirm that the in vivo images are truly reflective of the tissue concentration levels. The project ends with the study of microinvasion and testing the detection of this spontaneously and in the setting of anti-vascular therapy. The grant focuses on the technology development, methodology development about how optical fluorescence can be added usefully to imaging science, with these two potential applications in cancer.