Tomographic Molecular Imaging for Breast Cancer

乳腺癌的断层分子成像

• 批准号: 7882584
• 负责人: GULTEKIN GULSEN
• 金额: $ 32.48万
• 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/7882584
• 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（由申请人提供）：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。靶向且可激活的探针与特定靶标相互作用，因此可以在细胞或分子水平上对生物过程进行成像。靶向探针与特定靶标（例如受体）结合，可用于对受体表达和分布进行成像，而可激活探针可用于对基质降解酶（如 MMP 或组织蛋白酶）的活性进行成像。这种探针与光学成像一起可能会产生一种独特的、高度灵敏的技术，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，其中一些探针将可用于临床环境。然而，尽管分子成像技术取得了进步，但直到最近才开始致力于开发可用于乳腺癌成像临床环境的体内荧光增强光学断层扫描 (FDOT)。在此应用中，我们建议采用多模态方法，即组合的 MR/FDOT 动物成像系统，以提高 FDOT 的准确性，进而提高 MRI 区分良性和恶性乳腺癌的性能。多项研究证明，MRI 可以检测出乳房 X 光检查和超声检查中隐匿的恶性癌症，因此它已迅速成为筛查年轻女性的最流行的成像方式。然而，尽管 MRI 的敏感性很高，但特异性较低，因此它也可以检测到许多良性病变。作为该组合系统的对应部分，FDOT 将使用靶向/激活探针大幅提高 MRI 的特异性。同样，MRI 将通过提供先验信息来提高 FDOT 的定量准确性，这使得所提出的系统成为真正的多模态成像方法。一旦通过模型研究开发并优化了组合系统，将使用 MMP 敏感的可激活荧光成像探针和表达不同水平 MMP 活性的两种不同细胞系通过动物研究来评估系统的性能。本申请中提出的原理验证混合 MR/FDOT 成像模式是一种创新方法，也是迈向此类临床多模态成像系统的第一步。通过对设计进行适当修改，所提出的技术对于未来的人体临床试验具有巨大的转化潜力。 公众健康相关性 尽管乳房 X 光检查对于检测早期乳腺癌非常敏感，但对于因既往治疗而具有致密乳腺组织、乳房植入物或疤痕组织的女性，其效果不佳。乳腺 MRI 被认为是这些患者群体的最佳方式。然而，目前临床上可用的磁共​​振造影剂Gd-DTPA是一种低分子量的细胞外剂，在乳腺癌表征方面不能提供高特异性。与此同时，分子成像探针的最新发展表明，这些令人兴奋的探针很有可能在不久的将来用于临床。因此，我们集中精力使用荧光断层扫描系统作为 MRI 的辅助手段以及靶向/可激活探针来提高特异性。这些探针现在仅可用于动物成像，有必要通过动物研究来评估此类系统的性能。因此，本申请旨在开发一种用于大鼠成像的混合 MR/FDOT 系统。如果成功，该项目开发的仪器可以轻松修改用于临床乳腺成像，我们的努力成果将提供一种复杂的工具，可以在肿瘤的检测和表征中提供高灵敏度和高特异性。