In vivo Image Guided Cancer Therapy

描述（由申请方提供）：本提案的总体目标是研究在人类癌症临床前动物模型中使用多模态成像方法进行体内引导癌症治疗的潜力。随着癌症治疗的进展，化疗和遗传，能够确定其疗效变得至关重要，这对患者的总体生存至关重要。非侵入性成像技术目前可用于可视化人体的不同病理状况，但由于缺乏肿瘤特异性成像探针，它们用于癌症监测的用途受到限制。我们最近开发了一种多模式成像探针，靶向糖基化不足的粘蛋白-1肿瘤抗原（uMUC-1），这是多种肿瘤发生的早期标志之一。我们的肿瘤特异性多模态成像探针由用于MR成像的交联超顺磁性氧化铁纳米颗粒（克利奥）组成，用Cy5.5染料修饰（用于光学近红外成像，NIRF），并且具有连接到其葡聚糖涂层的特异性识别uMUC-1的肽。MUC-1在几乎所有人类上皮细胞腺癌中过表达和糖基化不足，包括超过90%的人类乳腺癌、胰腺癌、结肠直肠癌、肺癌、前列腺癌和胃癌。此外，uMUC-1表达已在非上皮癌细胞系以及血液恶性肿瘤如多发性骨髓瘤和一些B细胞非霍奇金淋巴瘤中得到证实。在本申请中，我们提出使用常规化疗剂以及新方法如siRNA技术来研究非侵入性监测肿瘤进展/消退中的治疗相关变化的可能性。我们还将评估肿瘤体积的变化，这可以使用CLIO-EPPT探针检测，并将我们使用该探针的结果与传统的动态对比增强磁共振成像（DCE MRI）与钆-DTPA（Gd-DTPA）进行比较。我们将评估化疗过程中uMUC-1的表达，并将其与CLIO-EPPT积累相关联。如果成功，这项研究可以进一步转化为临床应用，因为相关的氧化铁已经在临床试验中进行了测试。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to investigate the potential for in-vivo guided cancer therapies using the multi-modal imaging approach in pre-clinical animal models of human cancer. With the advances in cancer treatments, both chemotherapeutic and genetic, it becomes crucial to be able to determine their efficacy, which is crucial for overall patient survival. Non-invasive imaging techniques are currently available for visualizing different pathological conditions of the human body, but their use for cancer monitoring is limited due to the lack of tumor-specific imaging probes. We have recently developed a multi-modal imaging probe targeting the underglycosylated mucin-1 tumor antigen (uMUC-1), which is one of the early hallmarks of tumorigenesis in a wide variety of tumors. Our tumor-specific multi-modal imaging probe consists of crosslinked superparamagnetic iron oxide nanopartides (CLIO) for MR imaging, modified with Cy5.5 dye (for optical near-infrared imaging, NIRF), and has peptides, specifically recognizing uMUC-1, attached to its dextran coat. MUC-1 is overexpressed and underglycosylated on almost all human epithelial cell adenocarcinomas, including more than 90% of human breast cancers, pancreatic, colorectal, lung, prostate, and gastric carcinomas. Moreover, uMUC-1 expression has been demonstrated in non-epithelial cancer cell- lines, as well as in hematological malignancies, such as multiple myeloma and some B-cell non-Hodgkin lymphomas. In this application we propose to investigate the possibility of non-invasive monitoring of treatment-related changes in tumor progression/regression using conventional chemotherapeutic agents as well as novel approaches such as siRNA technology. We will also evaluate changes in tumor volume, which can be detected using the CLIO-EPPT probe and compare our findings using this probe with conventional dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with Gadolinium-DTPA (Gd-DTPA).We will evaluate uMUC-1 expression during the course of chemotherapy and correlate it with CLIO-EPPT accumulation. If successful, this study can further be translated into clinical applications, since related iron oxides have already been tested in clinical trials.