Diffused Optical Tomography using Oxygen-sensitive Luminescent Contrast Agent for

使用氧敏感发光造影剂的扩散光学断层扫描

• 批准号: 7404778
• 负责人: Rajan Gurjar
• 金额: $ 21.03万
• 依托单位: RADIATION MONITORING DEVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-28 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7404778
• 关键词: Address; Adult; Aftercare; Algorithms; Antibodies; Area; Biological Markers; Brain; Breast; Breast Cancer Cell; Breast Cancer Detection; Cancer Detection; Cancerous; Cell Line; Cells; Collaborations; Comb animal structure; Complex; Contrast Media; Count; Coupled; Data Analyses; Depth; Detection; Development; Distant; Dyes; Encapsulated; Endothelial Cells; Engineering; Epitopes; Family; Fluorescence; Fluorescent Probes; General Hospitals; Goals; Growth; Hypoxia; Image; Imaging Phantoms; Imaging Techniques; Injury; Invasive; Knowledge; Lasers; Lesion; Lighting; Link; Localized; Lung; Malignant Neoplasms; Massachusetts; Measurement; Medicine; Michigan; Modality; Monitor; Muscle; Noise; Numbers; Optics; Oxygen; Pennsylvania; Peptides; Performance; Phase; Phenotype; Photons; Physiologic pulse; Postoperative Period; Property; Pulse taking; Radiation Monitoring; Radiation, Other; Range; Reporting; Research; Resistance; Sampling; Scientist; Signal Transduction; Small Business Technology Transfer Research; Solid Neoplasm; Staging; Surface; System; Techniques; Time; Tissues; Tumor Specific Peptide; Universities; Width; Work; Writing; base; breast cancer diagnosis; cancer cell; cancer diagnosis; cancer imaging; concept; detector; diffuse optical tomography; experience; image processing; image reconstruction; improved; instrument; instrumentation; luminescence; malignant breast neoplasm; monitoring device; nanoparticle; nanosecond; nanosensors; neoplastic cell; optical imaging; outcome forecast; prototype; receptor; research study; success; time use; tissue phantom; tomography; tumor

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.

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成像的重要研究领域。癌症诊断和预后研究的目标是开发新的成像技术，以便在早期确定病变，以便进行治疗。开发生物标记物是癌症成像的主要推动力领域，它将发出病变存在和类型的信号。特别强调开发生物标记物，这些标记物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，我们将专注于使用基于近红外(NIR)的扩散光学断层扫描(DOT)技术来检测和成像缺氧性乳腺癌。通过使用针对与血管生长有关的特定癌细胞的造影剂，图像对比度将得到改善。在生长中的肿瘤中持续低氧会导致细胞的变化，从而导致侵袭性癌症表型。缺氧导致的进展往往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可能会增强。因此，有必要使用非侵入性成像技术监测深部组织缺氧性癌症，将其与非肿瘤特异性缺氧(即，由于身体损伤等)区分开来。辐射监测设备公司(RMD)与密歇根大学的Raul Kopelman博士合作，将开发一种近红外(NIR)漫反射光学断层扫描(DOT)仪器，用于使用基于多肽的发光造影剂检测乳腺癌。建议的造影剂将靶向血管内皮细胞或乳腺癌细胞。它将定位于肿瘤内，其发光强度和寿命对氧敏感。低氧合(缺氧)是局部晚期实体肿瘤的共同特征，可以作为生物标志物，因此该造影剂将为监测癌症肿瘤提供一种有效的方法。此外，为了提高现有DOT仪器的灵敏度并利用这一新的染料系列，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。使用合适的造影剂演示使用荧光寿命断层扫描的三维光学成像将为第二阶段原型的性能提供基线。

项目成果

Near infrared luminescent oxygen nanosensors with nanoparticle matrix tailored sensitivity.

• DOI: 10.1021/ac1015358
• 发表时间: 2010-10-15
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Lee, Yong-Eun Koo;Ulbrich, Elyse E.;Kim, Gwangseong;Hah, Hoejin;Strollo, Christen;Fan, Wenzhe;Gurjar, Rajan;Koo, Sang Man;Kopelman, Raoul
• 通讯作者: Kopelman, Raoul