MR AGENTS SENSITIVE TO BIOLOGICAL INDICATORS

对生物指标敏感的 MR 制剂

• 批准号: 7956955
• 负责人: Dean Sherry
• 金额: $ 1.78万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956955
• 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; Metabolism; 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. June-10-2009 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.

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