PARACEST Agents: Optimization for Human MR Imaging

PARACEST 代理：优化人体 MR 成像

• 批准号: 8431760
• 负责人: ROBERT E LENKINSKI
• 金额: $ 82.82万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8431760
• 关键词: Acceleration; Address; Albumins; Animals; Area; Binding; Blood Vessels; Buffers; Case Study; Chemicals; Chemistry; Clinical; Contrast Media; Detection; Development; Drug Kinetics; Environment; Europe; Evaluation; Family suidae; Frequencies; Funding; Gadolinium; Goals; Grant; Guidelines; Head; Human; Hypoxia; Image; In Vitro; Institution; International; Israel; Kidney; Kinetics; Knee; Knowledge; Label; Lanthanoid Series Elements; Lead; Ligands; Liver; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Medical center; Methodology; Methods; Modeling; Molecular Weight; Oxidation-Reduction; Paper; Perfusion; Physiologic pulse; Play; Polymers; Process; Progress Reports; Property; Proteins; Publishing; Radio; Rattus; Research; Research Personnel; Role; Side; Signal Transduction; Spin Labels; System; Testing; Theoretical model; Time; Tissue Model; Tissues; Toxic effect; Validation; Virion; Water; absorption; base; design; extracellular; gadolinium 1,4,7,10-tetraazacyclododecane-N,N' ,N' ' ,N' ' ' -tetraacetate; gadolinium oxide; imaging modality; in vivo; irradiation; meetings; method development; molecular imaging; novel strategies; public health relevance; research study; sensor; simulation; theories; tumor

DESCRIPTION (provided by applicant): Paramagnetic chemical exchange saturation transfer (PARACEST) agents offer a potential new paradigm in MR imaging. An advantage to this class of agents is the ability to switch each agent on or off through selective RF irradiation applied at the frequency of either its bound water resonance or an exchanging NH group. In their "off" state, i.e. when not specifically irradiated, PARACEST agents will not interfere with conventional MR imaging sequences, with or without gadolinium. In principle, PARACEST agents can be tailored to each application because their effects depend on their water exchange rates, and these rates can be modified using rational chemical principles. This feature also makes them an attractive platform for the development of responsive agents. The goal of this BRP is to realize the full potential of these compounds as contrast agents in vivo, by systematically addressing a number of basic, theoretical and practical questions. These include establishing the relationships among the magnitude of the effect measured in an imaging experiment and the water exchange lifetime, the magnitude of the chemical shift difference between the bound and bulk water, the strength of the saturating RF field, SAR, concentration, and local environment in vivo. This partnership is made up of two academic institutions and an industrial collaborator. The three main overlapping and interactive areas of focus are: lanthanide chemistry, which will be carried out at UT Dallas (UTD); Pulse sequence implementation, theory, simulations and in vitro validation which will be carried out primarily at the General Electric Global Research Center (GEGRC) and in vivo validation carried out primarily at the BIDMC. Dean Sherry (Project Leader, UTD) is an internationally recognized expert in the synthesis and characterization of lanthanide chelates and has expertise in basic NMR exchange theory. Thomas Dixon and Ileana Hancu (Project Leaders, GEGRC) are both experts in NMR and MR imaging. Robert Lenkinski (PI, BIDMC) is an NMR spectroscopist with expertise both in lanthanide agents and MR imaging. David Alsop (Lead Investigator, BIDMC) has a long track record in optimizing Arterial Spin Labeling perfusion studies, where the detection of small signal intensity changes in the presence of RF irradiation is necessary. Over the past several years, this team has been collaborating on the theoretical and practical aspects of the PARACEST effect. The successful completion of this project will result in three agents (intravascular, pH, and Redox responsive) and MR acquisition strategies for use in human studies.

描述（由申请人提供）：顺磁化学交换饱和转移（Paracest）代理在MR成像中提供了潜在的新范式。这类代理的优势是能够通过以其结合的水共振或交换NH组施加的选择性RF辐射开关或关闭每个代理的能力。在其“关闭”状态中，即当未特异性辐照时，最偏s的药物不会干扰有或没有gadolinium的常规MR成像序列。原则上，可以为每个应用程序量身定制最高的代理，因为它们的影响取决于其水汇率，并且可以使用合理的化学原理对这些速率进行修改。此功能也使它们成为开发响应代理的有吸引力的平台。该BRP的目的是通过系统地解决许多基本的，理论和实用的问题来实现这些化合物作为体内对比剂的全部潜力。其中包括建立在成像实验和水交换寿命中测得的效果的关系，结合水和散装水之间的化学位移差异的大小，饱和的RF场的强度，SAR，SAR，浓度和Vivo的局部环境。该合作伙伴关系由两个学术机构和一个工业合作者组成。重点的三个主要重叠和交互式领域是：灯笼化学，将在UT Dallas（UTD）进行；脉冲序列实施，理论，模拟和体外验证将主要在通用电气全球研究中心（GEGRC）和体内验证中进行，主要是在BIDMC进行的。 Dean Sherry（UTD项目负责人）是国际公认的灯笼螯合物合成和表征的专家，并且在基本NMR交换理论方面具有专业知识。 Thomas Dixon和Ileana Hancu（GEGRC项目负责人）都是NMR和MR Imaging的专家。罗伯特·兰金斯基（Robert Lenkinski）（PI，BIDMC）是一位NMR光谱学家，在灯笼代理和MR成像中都具有专业知识。 David ALSOP（BIDMC的主要研究员）在优化动脉自旋标记灌注研究方面具有较长的记录，其中需要在RF辐照的存在下检测小信号强度变化。在过去的几年中，该团队一直在最偏见的效果的理论和实践方面进行合作。该项目的成功完成将导致三种代理（血管内，pH和氧化还原反应）和MR获得的策略用于人类研究。