Functional, cellular, and molecular imaging and therapy monitoring using ultrasou

描述(申请人提供)：小动物模型，特别是基因工程小鼠，越来越被认为是癌症研究中强有力的发现工具。然而，动物模型的潜力尚未完全实现，因为它们经常被牺牲来进行组织分析，以确定治疗的效果。牺牲阻止了对自然或受干扰的过程的长期活体观察。因此，需要一种形态、功能、细胞/分子和定量成像技术，能够在体内和纵向上显示小动物体内的生化、遗传或药理过程。我们学术和产业合作的总体目标是实现超声引导光声(USPA)成像的分子和细胞敏感性，进一步开发并转化为纵向动物研究的临床前研究领域。我们的假设是，一个非侵入性的USPA成像系统，能够同时对小动物的癌症进行解剖、功能、细胞和分子可视化，将显著提高基础和临床前癌症研究的结果。我们应用程序的中心主题是开发用于USPA成像的造影剂和信号/图像处理算法，以实现对乳腺癌小动物模型中的肿瘤血管生成和组织的功能、细胞/分子特性的定量成像。在这个项目中，我们将通过开发对人表皮生长因子受体2(HER2)和1v23整合素敏感的成像造影剂来具体演示我们的方法。在纵向研究中，这些试剂将用于检测体内肿瘤的分子组成，以监测治疗性小分子酪氨酸激酶抑制剂拉帕替尼对乳腺癌细胞功能和血管生成的影响。

DESCRIPTION (provided by applicant): Small animal models, particularly genetically engineered mice, are increasingly recognized as powerful discovery tools in cancer research. However, the potential of animal models has not yet fully been realized since they are often sacrificed to perform tissue analysis to determine the effects of therapy. Sacrificing prevents long-term, in vivo observation of natural or perturbed processes. Therefore, there is a need for a morphologic, functional, cellular/molecular, and quantitative imaging technique capable of visualizing biochemical, genetic, or pharmacological processes in vivo and longitudinally in small animals. The overall goal of our academic-industrial partnership is to enable the molecular and cellular sensitivity of ultrasound-guided photoacoustic (USPA) imaging, furthering its development and translation into the preclinical research arena for longitudinal animal studies. Our hypothesis is that a non-invasive USPA imaging system, capable of simultaneous anatomical, functional, cellular and molecular visualization of cancer in small animals, will significantly enhance the outcome of fundamental and preclinical cancer research. The central theme of our application is to develop contrast agents and signal/image processing algorithms for USPA imaging to enable quantitative imaging of tumor angiogenesis and functional, cellular/molecular properties of tissue in small animal models of breast cancer. In this project we will specifically demonstrate our approach by developing imaging contrast agents sensitive to human epidermal growth factor receptor 2 (HER2) and the 1v23 integrin. These agents will be used to detect the molecular composition of a tumor in vivo to monitor the effect of the therapeutic small molecule tyrosine kinase inhibitor lapatinib on breast cancer cellular function and angiogenesis in longitudinal studies.