Tomographic Molecular Imaging for Breast Cancer

乳腺癌的断层分子成像

• 批准号: 7684027
• 负责人: GULTEKIN GULSEN
• 金额: $ 31.48万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7684027
• 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; Evaluation; 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; 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; pre-clinical; prevent; prototype; public health relevance; receptor; receptor expression; reconstruction; response; simulation; symposium; tomography; tool; treatment planning; 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(申请人提供)：用于分子成像的近红外光学探针的最新发展为乳腺癌成像带来了巨大的希望。靶向和可激活的探针与特定的靶点相互作用，从而使在细胞或分子水平上成像生物过程成为可能。靶向探针结合到特定的靶点，如受体，并可用于成像受体的表达和分布，而可激活的探针可用于成像基质降解酶的活性，如MMPs或组织蛋白酶。这样的探针与光学成像一起可能产生一种独特的、高度敏感的技术，用于体内肿瘤形成和转移的成像。不可避免的是，在不久的将来，其中一些探针将可用于临床设置。然而，尽管分子成像技术取得了进步，但直到最近，人们才专注于开发可用于乳腺癌临床成像的体内荧光增强光学断层扫描(FDOT)。在这一应用中，我们建议使用多模式方法，即MR/FDOT动物成像系统，以提高FDOT的准确性，进而提高MRI在区分乳腺癌和恶性乳腺癌方面的性能。几项研究已经证明，核磁共振可以检测出在乳房X光检查和超声波检查中隐匿的恶性肿瘤，因此它迅速成为年轻女性筛查中最受欢迎的成像方式。然而，尽管MRI的敏感性很高，但它的特异性很低，以至于它也能检测到许多良性病变。作为这一组合系统的对应物，FDOT将大大提高MRI的特异性，使用靶向/激活的探针。同样，MRI将通过提供先验信息来提高FDOT的定量精度，这使所提出的系统成为真正的多模式成像方法。一旦通过模体研究开发和优化组合系统，系统的性能将通过动物实验进行评估，方法是使用金属蛋白酶敏感的可激活荧光成像探针和两种表达不同水平金属蛋白酶活性的不同细胞系。本申请中提出的原理验证混合MR/FDOT成像模式是一种创新的方法，是迈向这种临床多模式成像系统的第一步。如果在设计上进行适当的修改，这项拟议的技术对未来的人类临床试验具有巨大的翻译潜力。 公共卫生相关性尽管乳房X光摄影在发现早期乳腺癌方面非常敏感，但对于因既往治疗而有致密的乳房组织、乳房植入物或疤痕组织的女性来说，它并不起作用。乳腺MRI被认为是这些患者群体中的最佳检查方式。然而，目前临床上可用的MR造影剂Gd-DTPA是一种低分子的细胞外造影剂，在乳腺癌的定性方面不能提供高的特异性。同时，分子成像探针的最新发展表明，在不久的将来，这些令人兴奋的探针很有可能用于临床。因此，我们致力于提高特异性，使用荧光断层成像系统作为MRI的辅助设备，并使用靶向/可激活的探针来提高特异性。这些探头现在只能用于动物成像，有必要通过动物实验来评估这种系统的性能。因此，本应用旨在开发一种用于大鼠成像的MR/FDOT混合系统。如果成功，在该项目期间开发的仪器可以很容易地进行修改，用于临床乳房成像，我们努力的结果将提供一种复杂的工具，可以在检测和表征肿瘤方面提供高灵敏度和高特异度。