MOLECULAR IMAGING OF METASTATIC LYMPH NODES IN BREAST CANCER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 乳腺癌的特征是癌细胞扩散到淋巴系统。对淋巴结的准确评估是确定疾病进展和患者随后可用的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切除术，这是一种对手术切除的淋巴结进行显微镜检查的方法。然而，这种痛苦和侵入性的手术会导致结节破坏和肿胀，在分析上并不总是可靠的。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受感染淋巴结的恶性程度，因为它们只显示结构，而没有揭示与疾病进展相关的生物活性。 我们试图通过检测一种已知的乳腺癌生物指标--组织蛋白酶-B来开发突出病变淋巴结的成像探针。组织蛋白酶-B在特定的氨基酸序列上对蛋白质进行酶解，这种活性与癌细胞通过破坏基底膜而侵入淋巴结有关。我们建议的分子探针利用组织蛋白酶-B的天然裂解活性作为一种特定的激活机制。非活性探针是一种非荧光化合物，由固定在定制氨基酸序列上的荧光染料和猝灭剂组成。它被组织蛋白酶-B激活为荧光物种，选择性地切断猝灭剂。这种“光开关”的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。 加州大学旧金山分校的质谱学设施拥有对我们建议的探测器进行表征的仪器和专业知识。对于我们的应用，质谱学提供了优于其他光谱工具的效率和易解性。

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 instrumentation 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.