In vivo Thermoacoustic Imaging of HER2 Status

描述(由申请人提供)： 在这一快速通道应用中，我们建议开发新的成像技术和分子探针，以实现对乳腺癌中HER2过度表达的非侵入性检测和定量。我们正在推广的方法是用红外吸收染料标记治疗性单抗Herceptin，然后使用多光谱红外刺激用热声计算机断层扫描(TCT)检测抗体/染料结合物的存在。在第一阶段，我们将验证一种多光谱分解技术，用于在不同数量的充氧和脱氧血液中量化红外吸收染料的存在。我们还将通过一系列组织模拟体模研究来量化1毫升体积内可检测到的最小染料浓度。在第二阶段，我们将与印第安纳大学医学中心的研究人员合作开发分子探针，并量化其与表达HER2的细胞的结合。我们还将改进我们的成像仪器，使我们能够获得超声和热声CT图像，这将是完美的Spatjal配准。小鼠将被用来在几个肿瘤模型中验证我们的方法，收集的数据和开发的设备用于建立将技术转移到人类的基础。 我们第一阶段的具体目标是： 1.设计、建造和测试包含球面聚焦、半圆形探测器阵列的TCT成像系统。 2.使用这一新的TCT成像系统验证了一种多光谱分解技术，该技术可以在存在氧合和脱氧血红蛋白的情况下定量测定IRIS Green One染料的浓度。 3.确定在乳房组织模拟体模的1.2 mm直径的管内可以检测到的IRIS Green One染料的最低可检测浓度。

DESCRIPTION (provided by applicant): In this Fast Track application, we propose developing the novel imaging technology and molecular probe that will enable the non-invasive detection and quantification of HER2 overexpression in breast cancers. The approach we are promoting is to label Herceptin, a therapeutic mono-clonal antibody, with an infraredabsorbing dye, and then to detect the presence of the anitbody/dye conjugate with thermoacoustic computed tomography (TCT) using multi-spectral infrared stimulation. In Phase I we will validate a muIti-spectral decomposition technique for quantifying the presence of an infrared-absorbing dye in the presence of varying amounts of oxygenated and deoxygenated blood. We will also quantify the minimum detectable concentration of dye within a 1-ml volume through a series of tissue-mimicking phantom studies. In Phase II we will collaborate with researchers at Indiana University Medical Center to develop the molecular probe and quantify its binding to HER2 expressing cells. We will also modify our imaging instrumentation to allow us to acquire ultrasound and thermoacoustic CT images, which will be in perfect spatjal registration. Mice will be used to validate our approach in several tumor models with the data collected and equipment developed used to build the foundation for transferring the technology to humans. Our specific Phase I aims: 1. Design, construct and test a TCT imaging system that incorporates a spherically focused, semi-circular detector array. 2. Validate a multi-spectral decomposition technique using this new TCT imaging system for quantifying the concentration of IRIS Green One dye in the presence of oxy- and deoxy-hemoglobin. 3. Determine the minimum detectable concentration of IRIS Green One dye that can be detected within a 1.2-mm diameter tube in a breast-tissue mimicking phantom.