Molecular, functional and micro-morphological imaging of bone metastases in vivo

体内骨转移的分子、功能和微形态学成像

• 批准号: 197529062
• 负责人: Professor Dr. Claus-Christian Glüer
• 金额: --
• 依托单位: Molecular Imaging North Competence Center (MOIN CC)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/197529062?language=en
• 关键词: Molecular; functional; micro; morphological; imaging

The complexity of the bone microenvironment and the multitude of cell types interacting with each other during skeletal metastasis necessitate the development of technologies suited for multimodal molecular, functional and micro-morphological imaging of these processes in vivo. We will test the hypothesis whether molecular markers specific for osteoblasts, osteoclasts and tumor cell interaction can be employed to allow for longitudinal monitoring of these cells during skeletal metastasis at the microstructural level. An optical reporter gene placed under the control of the osteoblast tissue-specific promoter, α1(I)-collagen, will allow to label cells of the osteoblastic lineage in an immunodeficient mouse strain. Imaging methods based on fluorescent markers reflecting osteoblast induced matrix apposition, osteoclast number (αvβ3 integrin) and function (cathepsin K expression) will be developed to study tumor-bone interaction, e.g. with regard to Dickkopf-1. Multi-modality imaging combining fluorescent molecular tomography (FMT) and micro-computed tomography (micro-CT) will be optimized for quantitative longitudinal evaluation. Our work will result in validation of a robust basic armamentarium of quantifiable FMT/micro-CT markers and methods with potential to image tumor-bone interaction-specific targets which are characterized in partner projects. Such methods will augment the ability to non-invasively monitor metastatic processes also in response to treatment.

骨微环境的复杂性和骨转移过程中相互作用的多种细胞类型需要开发适用于体内这些过程的多模态分子，功能和微形态成像的技术。我们将测试的假设是否可以采用成骨细胞，破骨细胞和肿瘤细胞相互作用的分子标记物，以允许纵向监测这些细胞在骨转移过程中的微观结构水平。光学报告基因置于成骨细胞组织特异性启动子α1（I）-胶原蛋白的控制下，将允许标记免疫缺陷小鼠品系中的成骨细胞谱系细胞。将开发基于反映成骨细胞诱导的基质沉积、破骨细胞数量（αvβ3整联蛋白）和功能（组织蛋白酶K表达）的荧光标记物的成像方法，以研究肿瘤-骨相互作用，例如Dickkopf-1。将优化结合荧光分子断层扫描（FMT）和微型计算机断层扫描（micro-CT）的多模态成像，以进行定量纵向评价。我们的工作将导致验证一个强大的基本医疗设备的可量化的FMT/micro-CT标记物和方法，有可能成像肿瘤-骨相互作用的具体目标，其特点是在合作伙伴项目。这样的方法将增强非侵入性监测也响应于治疗的转移过程的能力。