Fluorescence Imaging to Optimize Cancer Detection

描述(申请人提供)：定量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难以置信的潜力，但许多配体分子无法有效利用，因为它们不区分简单的基于血管通透性的摄取和真正的受体结合。发展方法，允许定量摄取肿瘤中的分子是这笔赠款在续期期间的主要重点。体内受体活性的荧光成像是使用一种新型的磁共振引导光学(MRGO)成像仪器进行的，该成像仪器是为小动物定制的，主要专注于胶质瘤肿瘤的研究。硬件和软件子系统将进一步开发，以提供在MR数据引导下的4层荧光断层扫描的体积数据，并覆盖整个原位肿瘤的可视化。这项工作的目标是分析如何使用胶质瘤肿瘤的分子示踪剂来有效地量化肿瘤受体的活性，以及如何从对比MRI中获得血管灌注。小分子表皮生长因子(EGF)作为探针与非特异性荧光团试剂一起使用表明，摄取的比率测量可以导致结合的EGF受体摄取的定量。这种新的探针分子可以检测到微侵袭的胶质瘤，因此无法用典型的磁共振成像检测到，双探针方法将被用来展示MRGO成像如何提供一种全新的方法来对这种疾病进行成像。设计了不同分子质量的高亲和力和低亲和力的比率成像探针，并进行了体外验证，以确认体内图像真实地反映了组织的浓度水平。该项目以对微侵袭的研究结束，并在抗血管治疗的背景下测试对这种微侵袭的检测。这笔赠款的重点是关于如何将光学荧光有效地添加到成像科学中的技术开发和方法开发，以及这两个在癌症中的潜在应用。

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.