Tomographic Molecular Imaging for Breast Cancer

乳腺癌的断层分子成像

• 批准号: 8091368
• 负责人: GULTEKIN GULSEN
• 金额: $ 31.07万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-05 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8091368
• 关键词: Abdominal Cavity; Adenocarcinoma; Algorithms; Animals; Anxiety; Area; Benign; Binding; Biological Process; Biomedical Engineering; Biopsy; Breast; Caliber; Cathepsins; Cell Line; Cicatrix; Clinical; Clinical Research; Clinical Trials; Complex; Contrast Media; Detection; Development; Devices; Diagnosis; Disease; Enzymes; Equation; Fiber; Fluorescence; Fluorescent Dyes; Fluorescent Probes; Future; Gadolinium DTPA; Gelatinase A; Goals; Guidelines; Health behavior; Heterogeneity; Human; Hybrids; Image; Imaging technology; Implant; Internal Breast Prosthesis; Joints; Knowledge; Laboratories; Lead; Lesion; Light; Literature; Location; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Ultrasonography; Mammography; Matrix Metalloproteinases; Measures; Medical; Medical Research; Medicine; Methods; Modality; Modeling; Modification; Molecular; Molecular Probes; Molecular Weight; Monitor; Mus; Neoplasm Metastasis; Nude Rats; Optical Tomography; Optics; Outcome; Patients; Performance; Play; Principal Investigator; Property; Publishing; Rattus; Research; Research Personnel; Research Project Grants; Resolution; Rhode Island; Role; Scheme; Science; Screening procedure; Sensitivity and Specificity; Series; Small Animal Imaging Systems; Source; Specificity; Speed; Stem cells; System; Technology; Testing; Three-Dimensional Imaging; Time; Tissues; Translations; Treatment outcome; Tube; Ultrasonography; United States National Institutes of Health; Woman; Work; anticancer research; base; cancer imaging; clinical application; clinical practice; data acquisition; design; detector; enzyme activity; extracellular; fibrosarcoma; fluorescence imaging; fluorophore; high risk; imaging modality; imaging probe; improved; in vivo; innovation; instrumentation; lifetime risk; light emission; malignant breast neoplasm; molecular imaging; new technology; novel; optical imaging; patient population; performance tests; posters; prevent; programs; prototype; public health relevance; receptor; receptor expression; reconstruction; response; simulation; symposium; tomography; tool; tumor

DESCRIPTION (provided by applicant): Recent development of NIR optical probes for molecular imaging holds great promise for breast cancer imaging. Targeted and activable probes interact with specific targets and therefore make it possible to image biological processes at the cellular or molecular level. Targeted probes bind to specific targets, such as receptors, and can be used to image receptor expression and distribution, while activable probes can be employed to image the activity of matrix-degrading enzymes such as MMPs or cathepsins. Such probes along with optical imaging may yield a unique, highly sensitive technology for in vivo imaging of tumor formation and metastasis. It is inevitable that in the near future some of these probes will be available for use in clinical settings. Despite the advances in molecular imaging technology, however, only recently efforts have been focused on developing in vivo fluorescent enhanced optical tomography (FDOT) that can be used in clinical settings for breast cancer imaging. In this application, we propose to employ a multi-modality approach, a combined MR/FDOT animal imaging system, to improve the accuracy of FDOT and in turn to improve the performance of MRI in distinguishing benign and malignant breast cancers. Several studies have proven that MRI detects malignant cancers which are occult on mammogram and ultrasound, and as such it has fast becoming the most popular imaging modality for screening young women. However, despite its high sensitivity, MRI has low specificity, such that it also detects many benign lesions. As a counterpart of this combined system, FDOT will increase the specificity of the MRI substantially using the targeted/activated probes. Similarly, MRI will improve the quantitative accuracy of FDOT by providing a-priori information, which makes the proposed system a true multi-modality imaging approach. Once the combined system is developed and optimized with phantom studies, the performance of the system will be evaluated with animal studies by using MMP sensitive activable fluorescence imaging probes and two different cell lines that express different levels of MMP activity. The proof-of-principle hybrid MR/FDOT imaging modality proposed in this application is an innovative approach and a first step towards such a clinical multi-modality imaging system. With appropriate modifications in design, the proposed technology has a great translational potential for future human clinical trials. PUBLIC HEALTH RELEVANCE Although mammography is very sensitive in detecting early breast cancer, it does not work well in women who have dense breast tissues, breast implants, or scar tissues due to previous treatment. Breast MRI is considered as the optimal modality in these patient populations. However, the currently available clinical MR contrast agent Gd-DTPA is a low molecular weight extracellular agent that does not provide high specificity in breast cancer characterization. In the mean time, the recent developments in the molecular imaging probes showed that it is very possible to have some of these exciting probes for clinical use in the near future. Therefore, we focused our efforts on to improve the specificity using a fluorescence tomography system as adjunct to MRI along with targeted/activable probes to increase the specificity. These probes are now only available for animal imaging and it is necessary to evaluate the performance of such a system with animal studies. Hence, this application is aimed at developing a hybrid MR/FDOT system for imaging of rats. If successful, the instrumentation developed during this project can be easily modified for clinical breast imaging and the outcome of our effort will offer a sophisticated tool that could provide high sensitivity and high specificity in the detection and characterization of tumors.

描述（由申请人提供）：分子成像的NIR光学探针的最新开发对乳腺癌成像具有很大的希望。靶向探针与特定靶标相互作用，因此可以在细胞或分子水平上成像生物过程。靶向探针与特定靶标（例如受体）结合，可用于图像受体表达和分布，而可活化探针可用于成像基质降解酶的活性，例如MMPS或组织蛋白酶。此类探针以及光学成像可能会产生一种独特的高度敏感技术，用于肿瘤形成和转移的体内成像。不可避免的是，在不久的将来，其中一些探针将用于临床环境。尽管分子成像技术取得了进步，但是，直到最近，努力才集中在开发体内荧光增强的光学层析成像（FDOT），可用于乳腺癌成像的临床环境。在此应用中，我们建议采用一种多模式方法，即一种组合的MR/FDOT动物成像系统，以提高FDOT的准确性，然后改善MRI在区分良性和恶性乳腺癌方面的性能。几项研究证明，MRI检测到乳房X线照片和超声波检查的恶性癌症，因此它已迅速成为筛查年轻女性的最受欢迎的成像方式。但是，尽管其灵敏度很高，但MRI的特异性较低，因此它也检测到许多良性病变。作为该组合系统的对应物，FDOT将使用靶向/激活的探针实质上提高MRI的特异性。同样，MRI将通过提供A-Priori信息来提高FDOT的定量准确性，这使得拟议的系统成为真正的多模式成像方法。一旦通过幻影研究开发并优化了组合的系统，将通过动物研究评估系统的性能，并使用MMP敏感的可激活荧光成像探针和两种表达不同水平MMP活性的不同细胞系进行评估。本应用程序中提出的原则混合MR/FDOT成像方式是一种创新的方法，也是迈向这种临床多模式成像系统的第一步。通过在设计方面进行了适当的修改，该提议的技术具有未来人类临床试验的巨大转化潜力。 公共卫生相关性尽管乳房X线摄影在检测早期乳腺癌方面非常敏感，但由于先前治疗而患有密度致密的乳房组织，乳房植入物或疤痕组织的女性，它的效果不佳。乳房MRI被认为是这些患者人群中的最佳方式。但是，当前可用的临床MR造影剂GD-DTPA是一种低分子量细胞外剂，在乳腺癌表征中不提供高特异性。同时，分子成像探针的最新发展表明，在不久的将来，很有可能将其中一些令人兴奋的探针用于临床使用。因此，我们将精力集中在使用荧光断层扫描系统以及MRI以及靶向/可活动探针以提高特异性方面的辅助性方面提高特异性。这些探针现在仅用于动物成像，有必要评估通过动物研究的这种系统的性能。因此，该应用旨在开发用于大鼠成像的混合MR/FDOT系统。如果成功，则可以轻松地修改该项目期间开发的仪器，以进行临床乳房成像，我们的努力结果将提供一种复杂的工具，可以在肿瘤的检测和表征方面具有高灵敏度和高特异性。