In vivo Image Guided Cancer Therapy

体内图像引导癌症治疗

• 批准号: 7268004
• 负责人: ANNA MOORE
• 金额: $ 16.1万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-05 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268004
• 关键词: Adenocarcinoma; Animal Model; Apoptosis; Apoptotic; B-Cell NonHodgkins Lymphoma; CA-15-3 Antigen; Cancer cell line; Clinical Trials; Colorectal; Condition; Dextrans; Disease regression; Down-Regulation; Dyes; Effectiveness; Epithelial; Epithelial Cells; Gadolinium DTPA; Gene Silencing; Genetic; Goals; Hematologic Neoplasms; Histology; Human; Human body; Image; Imaging Techniques; Invasive; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Mediating; Methods; Monitor; Mucin 1 protein; Multiple Myeloma; Optics; Outcome; Pancreas; Patients; Peptides; Pre-Clinical Model; Prostate; Protein Overexpression; Proteins; RNA Interference; Route; Small Interfering RNA; Stomach Carcinoma; Technology; Testing; Translating; Tumor Antigens; Tumor Volume; albumin-(gadolinium-DTPA); cancer therapy; chemotherapeutic agent; chemotherapy; clinical application; crosslink; dextran; imaging probe; improved; in vivo; iron oxide; malignant breast neoplasm; nanoparticle; non-invasive monitor; novel strategies; pre-clinical; research study; response; success; survivin; tumor; tumor progression; tumorigenesis

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.

描述(由申请人提供)：这项提案的总体目标是在人类癌症的临床前动物模型中调查使用多模式成像方法进行体内指导癌症治疗的可能性。随着癌症治疗的进步，无论是化疗还是遗传治疗，能够确定它们的疗效变得至关重要，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不同的病理状况，但由于缺乏肿瘤特异性成像探针，它们在癌症监测中的应用有限。我们最近开发了一种针对低糖基化粘蛋白-1肿瘤抗原(UMUC-1)的多模式成像探针，UMUC-1是多种肿瘤发生的早期标志之一。我们的肿瘤特异性多模式成像探针由用于磁共振成像的交联型超顺磁性纳米氧化铁(CLIO)组成，用Cy5.5染料(用于光学近红外成像，NIRF)修饰，并在其葡聚糖涂层上附着了专门识别UMUC-1的多肽。MUC-1在几乎所有的人类上皮细胞腺癌中都是过度表达和糖基化的，包括90%以上的人类乳腺癌、胰腺癌、结直肠癌、肺癌、前列腺癌和胃癌。此外，UMUC-1在非上皮性癌细胞系以及血液系统恶性肿瘤中也有表达，如多发性骨髓瘤和一些B细胞性非霍奇金淋巴瘤。在这项应用中，我们建议使用传统的化疗药物和新的方法，如siRNA技术，研究非侵入性监测肿瘤进展/消退中与治疗相关的变化的可能性。我们还将评估使用CLIO-EPPT探头可以检测到的肿瘤体积的变化，并将使用该探头的结果与传统的Gd-DTPA动态对比增强磁共振成像(DCE MRI)进行比较。我们将评估UMUC-1在化疗过程中的表达并将其与CLIO-EPPT积聚相关联。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。