TARGETED METAL CHELATORS FOR DIAGNOSTIC IMAGING

人们对金属在医学上的应用很感兴趣。 镓、铟、镓和锶。镓的放射性同位素， 铟和锶在医学成像中被广泛使用，而镓 已被提议用作顺磁性造影剂 用核磁共振成像。在这项提案中，计划 合成能够与镓结合的新型低分子配体， 铟、Gd，在某些情况下，具有高稳定性的氚 常量。配体的结构将被设计成既 将产生与金属的亲水性和亲脂性络合物，并 还可以形成带正电荷和负电荷的络合物。 这四种金属的新配体的稳定常数为 测定和测定与血浆蛋白的交换率。在这 这些化合物的络合物的平衡和动力学稳定性 配体将被计算出来。标记化合物的生物分布 将首先在老鼠身上确定，在某些情况下，在狗和 灵长类动物。有希望的配体将被连接到单抗上，并 用镓、铟或锶标记的单抗。 然后将这些标记的抗体与体内的抗体进行比较 用当前的技术贴上标签。将研究Gd络合物。 体内和体外作为顺磁核磁共振对照的潜在用途 探员们。在这种情况下，复合体的宏观数量将是 将对这些络合物的稳定性进行详细的研究 被执行。

There is considerable interest in the application in medicine of the metals gallium, indium, gadolinium, and technetium. Radioisotopes of gallium, indium, and technetium are widely used in medical imaging, while gadolinium has been proposed for use as a paramagnetic contrast agent in conjunction with nuclear magnetic resonance imaging. In this proposal it is planned to synthesize new low molecular weight ligands capable of binding gallium, indium, gadolinium, and in some cases, technetium with high stability constants. The structure of the ligands will be designed such that both hydrophilic and lipophilic complexes with the metals will be produced and also so that complexes with positive and negative charges can be formed. The stability constants of the new ligands wit the four metals will be determined and the rate of exchange with plasma proteins measured. In this way both the equilibrium and kinetic stability of the complexes of these ligands will be calclulated. The biodistribution of the labeled compounds will be determined initially in rats and, in some cases, in dogs and primates. Promising ligands will be attached to monoclonal antibodies and the monoclonal antibodies labeled with gallium, indium, or technetium. These labeled antibodies will then be compared in vivo with antibodies labeled using current technology. The gadolinium complexes will be studied in vivo and in vitro for potential use as paramagnetic NMR contrast agents. In this case as macroscopic amounts of the complex will be administered, detailed studies on the stability of these complexes will be carried out.