Diffused Optical Tomography using Oxygen-sensitive Luminescent Contrast Agent for

描述（申请人提供）：分子特异性靶向和提高图像对比度已被公认为癌症影像学的重要研究领域。癌症诊断和预后研究的目标是开发新的成像技术，在早期阶段确定地发现病变，以便治疗。开发生物标志物，这将表明病变的存在和类型是癌症成像的主要推力领域。特别强调的是开发生物标志物，这将预测治疗后侵袭性和非侵袭性癌症的发展。在这项工作中，我们将重点研究使用基于近红外（NIR）的扩散光学断层扫描（DOT）技术检测和成像缺氧乳腺癌。通过使用造影剂靶向与血管生长有关的特定癌细胞，可以提高图像对比度。在生长中的肿瘤中持续的缺氧会引起细胞的变化，从而导致侵袭性的癌症表型。缺氧驱动的进展常导致局部侵袭性生长、病灶周围肿瘤细胞扩散和远处细胞肿瘤扩散。同样，对辐射和其他治疗的抵抗力也会增强。因此，有必要使用无创成像技术监测深部组织缺氧癌，将其与非癌症特异性缺氧（即由于物理损伤等）区分开来。辐射监测设备公司（RMD）将与密歇根大学的Raoul Kopelman博士合作，开发一种近红外（NIR）扩散光学断层扫描（DOT）仪器，用于使用基于肽的发光造影剂检测乳腺癌。建议的造影剂将针对血管内皮细胞或乳腺癌细胞。它将局限于肿瘤内，其发光强度和寿命对氧敏感。由于缺氧是局部晚期实体瘤的共同特征，因此可以作为生物标志物，因此所提出的造影剂将提供一种有效的监测癌性肿瘤的方法。此外，为了提高现有DOT仪器的灵敏度和利用这种新染料家族，提出了对光学系统的改进，包括使用灵敏的盖革模式雪崩探测器（GPD）和使用相关技术。演示三维光学成像使用荧光寿命断层扫描与合适的造影剂将提供一个基线的性能第二阶段的原型。

DESCRIPTION (provided by applicant): Molecule specific targeting and improving image contrast have been recognized as important research areas in cancer imaging. Goal of cancer diagnosis and prognosis research is to develop new imaging techniques to detect lesions with certainty in early stages so that they can be treated. Developing biomarkers, which will signal the presence and the type of lesion is a major thrust area in cancer imaging. Special emphasis is on developing biomarkers, which will predict the development of invasive and non-invasive cancer after treatment. In this work, we will focus on detecting and imaging hypoxic breast cancer using near-infrared (NIR) based diffused optical tomography (DOT) technique. Image contrast will be improved by using contrast agents targeting specific cancer cells involved with vasculature growth. Persisting hypoxia in a growing tumor can cause changes in the cells leading to aggressive cancer phenotype. Hypoxia driven progression often leads to local invasive growth, perifocal tumor cell spreading and distant cell tumor spreading. Similarly resistance to radiation and other treatments may become enhanced. Hence, it is necessary to monitor deep tissue hypoxic cancers, distinguish them from non-cancer specific hypoxia (i.e., due to physical injury etc.,) using a non-invasive imaging technique. Radiation Monitoring Devices, Inc (RMD) in collaboration with Dr. Raoul Kopelman from University of Michigan, will develop a near infrared (NIR) diffused optical tomography (DOT) instrument for breast cancer detection using peptide based luminescent contrast agent. The proposed contrast agent will target endothelial cells lining the vasculature or breast cancer cells. It will be localized within tumor and its luminescence intensity and lifetime will be oxygen- sensitive. Because poor oxygenation (hypoxia), which is a common feature of locally advanced solid tumors, can be utilized as a biomarker, the proposed contrast agent will provide an efficient way to monitor cancerous tumors. In addition, to advance the sensitivity of existing DOT instruments and take advantage of this new family of dyes, improvements to the optical system are proposed which includes use of sensitive Geiger mode avalanche detectors (GPD) and use of correlation technique. Demonstrating three-dimensional optical imaging using fluorescent lifetime tomography with a suitable contrast agent will provide a baseline for the performance of the Phase II prototype.