MOLECULAR IMAGING OF METASTATIC LYMPH NODES IN BREAST CANCER

乳腺癌转移淋巴结的分子成像

• 批准号: 8169777
• 负责人: Ella Fung Jones
• 金额: $ 3.71万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169777
• 关键词: Amino Acid Sequence; Basement membrane; Biological; Cancerous; Cathepsins; Cathepsins B; Cells; Cleaved cell; Computer Retrieval of Information on Scientific Projects Database; Disease; Disease Progression; Fluorescent Dyes; Funding; Grant; Image; Imaging Techniques; Institution; Light; Lymph; Lymphatic System; Malignant Neoplasms; Mass Spectrum Analysis; Molecular Probes; Nodal; Pain; Patients; Procedures; Proteins; Research; Research Personnel; Resources; Source; Structure; Swelling; Therapeutic; United States National Institutes of Health; design; imaging probe; instrumentation; lymph nodes; malignant breast neoplasm; molecular imaging; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Breast cancer malignancy is characterized by the spreading of cancerous cells into the lymphatic system. Accurate assessment of lymph nodes is a critical component in determining disease progression and subsequent therapeutic options available to patients. Currently, the most common practice of assessing lymph nodes is lymphadecnectomy, a microscopical examination of surgically removed lymph nodes. However, this painful and invasive procedure, which causes nodal destruction and swelling, is not always analytically reliable. Molecular imaging affords non-invasive options for visualizing lymph nodes. However, imaging techniques cannot accurately ascertain the malignancy of the infected lymph nodes, because they display only structures without revealing the bioactivities associated with disease progressions.We seek to develop imaging probes that highlight diseased lymph nodes by detecting a known breast cancer's biological indicator, Cathepsin-B. Cathepsin-B enzymatically cleaves proteins at specific amino acid sequences, and this activity is implicated in the invasion of cancerous cells into they lymph nodes by breaking down the basement membranes. Our proposed molecular probe utilizes Cathepsin-B's native cleaving activity as a specific activation mechanism. The inactive probe is a non-fluorescent compound composed of fluorescent dyes and quenchers attached onto a customized sequence of amino acids. It is activated to the fluorescent species by Cathepsin-B, which selectively cuts off the quenchers. This 'light switch' design reveals specific bioactivity information, which paves the way for non-invasive analytical imaging of lymph nodes.UCSF Mass Spectrometry Facility has the instrumentations and expertise for the characterization of our proposed probes. Mass spectrometry offers efficiency and ease of interpretation that is superior to other spectroscopic tools for our applications.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 乳腺癌恶性肿瘤的特征是将癌细胞扩散到淋巴系统中。 淋巴结的准确评估是确定疾病进展和随后可用于患者的治疗选择的关键组成部分。目前，评估淋巴结的最常见做法是淋巴结切除术，这是对手术去除的淋巴结的微观检查。但是，这种痛苦和侵入性的程序并不总是在分析上可靠的。分子成像提供可视化淋巴结的非侵入性选择。 但是，成像技术无法准确确定感染淋巴结的恶性肿瘤，因为它们仅显示结构而不揭示与疾病进度相关的生物活性。我们试图通过检测一种已知的乳腺癌的生物学指示剂，patherpsin-b来突出淋巴结的成像探针。组织蛋白酶-B酶促在特定的氨基酸序列上切割蛋白质，该活性与癌细胞的侵袭通过分解基底膜来侵入癌细胞进入淋巴结。我们提出的分子探针利用组织蛋白酶-B的天然分裂活性作为特定的激活机制。非活性探针是一种非荧光化合物，该化合物由荧光染料和附着在定制的氨基酸序列上的淬灭剂组成。它被组织蛋白酶B激活至荧光物种，该物种有选择地切断了淬火器。这种“照明开关”设计揭示了特定的生物活性信息，这为淋巴结的非侵入性分析成像铺平了道路。UCSF质谱设施具有仪器和专业知识，以表征我们所提出的探针。 质谱法提供了效率和易于解释，比其他光谱工具优于我们的应用。