In vivo Thermoacoustic Imaging of HER2 Status

HER2 状态的体内热声成像

• 批准号: 6929566
• 负责人: ROBERT A KRUGER
• 金额: $ 20.53万
• 依托单位: OPTOSONICS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-07 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6929566
• 关键词: bioimaging /biomedical imaging; biomarker; biomedical equipment development; breast neoplasm /cancer diagnosis; dyes; immunoconjugates; infrared radiation; molecular /cellular imaging; monoclonal antibody; oxyhemoglobin; phantom model; protooncogene; reagent /indicator; technology /technique development; thermography; tomography; ultrasonography

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.

描述（由申请人提供）： 在这种快速应用中，我们提出了开发新型的成像技术和分子探针，该探针将使乳腺癌中HER2过表达的非侵入性检测和定量。我们促进的方法是用红外染料染料标记赫斯蒂汀（一种治疗性的单链抗体，然后使用多光谱型红外刺激刺激染料染料，然后检测与热声计算机断层扫描（TCT）的Anitbody/Dye共轭物（TCT）。在第一阶段，我们将验证一种MUITI-Spentral分解技术，以量化在存在不同量的氧化和去氧血液的情况下存在红外吸收染料的存在。我们还将通过一系列模拟组织的幻影研究来量化1-ML体积内染料的最小染料浓度。 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HER2表达细胞的结合。 我们还将修改成像仪器，使我们能够获得超声和热声CT图像，这将是完美的Spatjal登记。通过收集的数据，将使用小鼠在几种肿瘤模型中验证我们的方法，并开发了用于将技术转移给人类的基础的设备。 我们的特定阶段目标是： 1。设计，构造和测试一个结合了球形的半圆形检测器阵列的TCT成像系统。 2。使用这种新的TCT成像系统验证多光谱分解技术，用于在存在氧和脱氧 - 血红蛋白的情况下量化虹膜绿色的一染料的浓度。 3。确定可以在模仿幻影的胸部组织中直径1.2毫米直径内检测到的虹膜绿色染料的最小可检测浓度。