MOLECULAR IMAGING OF METASTATIC LYMPH NODES IN BREAST CANCER

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 乳腺癌恶性肿瘤的特征是癌细胞扩散到淋巴系统。 淋巴结的准确评估是确定疾病进展和患者后续治疗方案的关键组成部分。目前，评估淋巴结最常见的做法是淋巴结切除术，手术切除淋巴结的显微镜检查。然而，这种痛苦和侵入性的程序，它会导致淋巴结破坏和肿胀，并不总是可靠的分析。分子成像为淋巴结的可视化提供了非侵入性的选择。 然而，成像技术不能准确地确定感染淋巴结的恶性程度，因为它们只显示结构，而不显示与疾病进展相关的生物活性。我们寻求开发成像探针，通过检测已知的乳腺癌的生物学指标，组织蛋白酶-B，突出病变淋巴结。组织蛋白酶-B在特定的氨基酸序列处酶促切割蛋白质，并且这种活性与癌细胞通过破坏基底膜而侵入淋巴结有关。我们提出的分子探针利用组织蛋白酶-B的天然切割活性作为特定的激活机制。非活性探针是由附着在定制的氨基酸序列上的荧光染料和猝灭剂组成的非荧光化合物。它被组织蛋白酶-B激活为荧光物质，组织蛋白酶-B选择性地切断淬灭剂。这种“光开关”设计揭示了特定的生物活性信息，为淋巴结的非侵入性分析成像铺平了道路。UCSF质谱设备具有表征我们提出的探针的仪器和专业知识。 对于我们的应用，质谱法提供了优于其他光谱工具的效率和易于解释的上级。

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.