Imaging Complex Molecular Signatures in Cancer

癌症中复杂分子特征的成像

• 批准号: 7318654
• 负责人: ANN-MARIE BROOME
• 金额: $ 9.42万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-13 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7318654
• 关键词: Animals; Antibodies; Binding; Biological; Biological Markers; Cell Surface Proteins; Cell surface; Cells; Chimeric Proteins; Clinic; Complement; Complex; Data; Detection; Development; Development Plans; Diagnostic; Disease; Disease Marker; Engineering; Enzymes; Facility Construction Funding Category; Faculty; Gene Expression; Genes; Goals; Half-Life; Image; Imaging technology; In Situ; In Vitro; Invasive; Knowledge; Laboratories; Learning; Ligands; Malignant Neoplasms; Mammalian Cell; Measures; Modality; Molecular; Molecular Profiling; Molecular Target; Natural regeneration; Normal tissue morphology; Physiology; Proteins; Reporting; Research; Research Personnel; Sensitivity and Specificity; Signal Transduction; Supervision; Surface; Techniques; Technology; Testing; Time; Tissues; Tumor Markers; Universities; antibody conjugate; career; cellular targeting; design; disease classification; experience; imaging probe; in vivo; molecular imaging; novel; programs; receptor; research study; skills; tool development; tumor

DESCRIPTION (provided by applicant): Molecular imaging has successfully been utilized in the recent past as a technology for imaging various aspects of mammalian physiology. However, the information that can be obtained using these non-invasive modalities is limited since it relies on the expression and imaging of single gene markers. While this information is useful, it can be misleading. For example, markers over-expressed in diseases tissues are also expressed in normal tissues in a spatio-temporal manner making interpretation of the results in a diagnostic setting potentially difficult. Several studies have demonstrated a high degree of both sensitivity and specificity for the identification and molecular classification of diseases by measuring the expression of multiple disease-associated changes in gene expression. The simultaneous over-expression of more than one of these gene markers is, therefore, more predictive of the disease state. Until now, molecular imaging was unable to image more than one marker at a time, requiring either different imaging technologies to be utilized simultaneously or requiring different probes with short biological half-lives to be imaged in rapid succession. The goal of the proposed study is to develop an imaging paradigm that will allow the detection and imaging of multiple over-expressed cancer disease targets at the same time. In the experiments proposed here we will attempt to conjugate these domains to each of three different ligands to simultaneously target and image, via enzyme re-construction in situ, three different molecular imaging targets. Application of this imaging paradigm will be conducted in vivo with animals bearing tumors that express either a subset or all of the biomarkers required for trans complementation. The proposed career development plan will offer the candidate protected time to further develop her research skills by learning new laboratory techniques, taking selective didactic coursework, and expanding her knowledge and experience in the practical conduct of experimentation both in the laboratory and in the clinic under the close supervision of experienced sponsors with input from consultants, collaborators, colleagues, and other faculty within the University.

描述（由申请人提供）： 分子成像在最近的过去已成功地被用作成像哺乳动物生理学各个方面的技术。但是，可以使用这些非侵入性方式获得的信息受到限制，因为它依赖于单基因标记的表达和成像。尽管此信息很有用，但它可能会产生误导。例如，在疾病组织中过表达的标记在正常组织中也以时空方式表达，从而在诊断环境中解释结果可能很困难。几项研究表明，通过测量基因表达中多种疾病相关变化的表达，对疾病的鉴定和分子分类具有高度的敏感性和特异性。因此，这些基因标记中多种的同时过表达更为可以预测疾病状态。到目前为止，分子成像一次都无法一次对一个以上的标记进行映像，需要同时使用不同的成像技术，或者需要具有短生物学半衰期的不同探针以快速连续成像。拟议的研究的目的是开发成像范式，该范式将同时检测和成像多种过表达的癌症疾病靶标。在此处提出的实验中，我们将尝试通过酶重建三个不同的分子成像靶标将这些域与三种不同的配体中的每一个共轭，以同时靶向和图像。该成像范式的应用将在体内与带有肿瘤的动物表达子群或反式互补所需的所有生物标志物。拟议的职业发展计划将为候选人提供受保护的时间，以通过学习新的实验室技术，进行选择性的教学课程以及在实验室和诊所的实际实验中扩展她的知识和经验，以进一步发展她的研究技能，并在经验丰富的诊所中，在经验丰富的赞助商的密切监督下，在顾问，合作者，合作社，同事以及其他院子内以及大学内的合作者，同事的投入。