Molecular Modeling in Metal Based Imaging Agent Design

金属显像剂设计中的分子建模

• 批准号: 6400376
• 负责人: DAVID E. REICHERT
• 金额: $ 15.9万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6400376
• 关键词: P glycoprotein; X ray crystallography; chemical models; chemical structure function; computer simulation; conformation; copper; gadolinium; gallium; hydropathy; ionic bond; molecular dynamics; radiochemistry; radiopharmacology; stereochemistry; technetium

Metal based radio pharmaceuticals are widely used in diagnostic imaging and radiotherapy. Molecular modeling is an under utilized tool in understanding the in vivo behavior of radiometal complexes and designing new radiometal based imaging and the therapeutic agents. A major goal of this work will involve the development of new force fields for metals of interest in imaging modalities such as SPECT, PET and MRI, these include copper, gallium, indium, technetium, and gadolinium. A second goal is the development of computer based methods for predicting the octanol/water partition coefficient for metal chelate complexes. A third goal will be probing the relationship between the structural and electronic natures of metal- bifunctional chelate (BFC) complexes and the biological behavior of metal BFC-biomolecule conjugates. The development of such tools will significantly aid the development of new metal based imaging and potentially therapeutic agents. Molecular mechanics force fields for metals of interest will allow the prediction of stability, charge, and lipophilicity all of which significantly affects the in vivo behavior of the metal-ligand complex. At present the dearth of computer aided molecular design techniques which can handle metal chelate complexes hinders the rapid development of the new metal based imaging agents with their unique radiochemical or magnetic behaviors.

基于金属的放射性药物广泛用于诊断成像和放射治疗。分子模型是理解放射性金属配合物的体内行为和设计新的基于放射性金属的成像和治疗剂的一种未充分利用的工具。这项工作的一个主要目标是为SPECT、PET和MRI等成像模式中感兴趣的金属开发新的力场，这些金属包括铜、镓、铟、锝和钆。第二个目标是开发基于计算机的方法，用于预测金属螯合物的辛醇/水分配系数。第三个目标是探索金属-双功能螯合物（BFC）络合物的结构和电子性质与金属BFC-生物分子缀合物的生物学行为之间的关系。这些工具的开发将大大有助于开发新的金属基成像和潜在的治疗剂。感兴趣的金属的分子力学力场将允许预测稳定性、电荷和亲脂性，所有这些都显着影响金属-配体络合物的体内行为。目前，由于缺乏计算机辅助的金属螯合物分子设计技术，阻碍了具有独特放化或磁性的新型金属显像剂的快速发展。