Molecular Modeling in Metal Based Imaging Agent Design

金属基放射药物广泛应用于影像诊断和放射治疗。分子模拟是了解放射性金属复合物在体内行为和设计新的放射金属成像和治疗剂的一种未被充分利用的工具。这项工作的一个主要目标将涉及为成像模式（如SPECT、PET和MRI）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来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）配合物的结构和电子性质与金属BFC-生物分子偶联物的生物学行为之间的关系。这些工具的发展将极大地帮助开发新的基于金属的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复合物的体内行为。目前，计算机辅助分子设计技术的缺乏阻碍了新型金属基显像剂的快速发展，这些显像剂具有独特的放射化学或磁性行为。

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.