MR AGENTS SENSITIVE TO BIOLOGICAL INDICATORS

对生物指标敏感的 MR 制剂

• 批准号: 8171640
• 负责人: Dean Sherry
• 金额: $ 1.05万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171640
• 关键词: Adenoviruses; Antibodies; Binding; Biological; Biological Process; Characteristics; Chemicals; Clinical; Complex; Computer Retrieval of Information on Scientific Projects Database; Contrast Media; Detection; Environment; Funding; Glucose; Goals; Grant; Hypoxia; Image; Institution; Ligands; Magnetic Resonance Imaging; Malignant Neoplasms; Membrane Proteins; Modeling; Nuclear; Optics; Oxidation-Reduction; Physiology; Proteins; Research; Research Personnel; Resources; Serine; Source; Surface; System; Tertiary Protein Structure; Time; Tissues; United States National Institutes of Health; Water; base; extracellular; imaging modality; improved; in vivo; molecular imaging; neoplastic cell; novel strategies; particle; sensor; small molecule; soft tissue

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. The major goals of this project are to develop applications of paramagnetic chemical exchange saturation transfer (PARACEST) imaging agents when bound to antibody surfaces and as small molecule sensors of hypoxia. MRI is the imaging modality of choice for soft tissue imaging but in general lacks sufficient sensitivity for molecular imaging of biological processes associated with cancer. Although Gd-based contrast agents are widely used in clinical MRI as non-specific extracellular agents, new approaches need to be developed to bring MRI into competition with optical and nuclear molecular imaging modalities. Paramagnetic complexes based on chemical exchange saturation transfer (PARACEST) offer a new mechanism for MRI contrast that could potentially improve sensitivity substantially and at the same time offer the unique ability to modulate imaging contrast (on/off) plus reflect specific tissue environments or physiology (pH, redox state, glucose levels). The first aim is to develop bifunctional ligands based on PARACEST for attachment to protein surface residues. These will be attached to model proteins and the water exchange characteristics of the resulting products will be evaluated and the lower detection limit of these systems evaluated by MRI. Two specific targeting systems will be evaluated, a phosphatidyl serine antibody and adenovirus particles with modified knob domain proteins, with the goal of creating activatible PARACEST systems that are completely "off" unless bound to their intended targets in vivo. A PARACEST agent will be developed that is trapped only in hypoxic tumor cells. The overriding goal of this project is to develop a new paradigm of molecular imaging agents for anatomical MR imaging of cancer based upon high sensitivity PARACEST agents.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的主要目标是开发顺磁性化学交换饱和转移（PARACEST）成像剂结合到抗体表面时的应用，并作为缺氧的小分子传感器。MRI是软组织成像的首选成像方式，但通常对于与癌症相关的生物过程的分子成像缺乏足够的灵敏度。虽然钆基造影剂作为非特异性细胞外试剂广泛用于临床MRI，但需要开发新的方法来使MRI与光学和核分子成像模式竞争。 基于化学交换饱和转移（PARACEST）的顺磁性复合物为MRI对比度提供了一种新的机制，其可以潜在地显著提高灵敏度，同时提供调节成像对比度（开/关）以及反映特定组织环境或生理学（pH、氧化还原状态、葡萄糖水平）的独特能力。 第一个目标是开发基于PARACEST的双功能配体，用于连接到蛋白质表面残基。 这些将附着于模型蛋白质，并将评价所得产物的水交换特性，并通过MRI评价这些系统的检测下限。 将评估两种特异性靶向系统，磷脂酰丝氨酸抗体和具有修饰的结结构域蛋白的腺病毒颗粒，其目标是创建可活化的PARACEST系统，该系统完全“关闭”，除非在体内与其预期靶标结合。 将开发仅在缺氧肿瘤细胞中捕获的PARACEST试剂。 该项目的首要目标是开发一种新的分子成像剂的范例，用于基于高灵敏度PARACEST剂的癌症解剖MR成像。