TARGETED METAL CHELATORS FOR DIAGNOSTIC IMAGING

人们对金属在医学上的应用很感兴趣 镓、铟、钆和锝。 镓的放射性同位素， 铟和锝广泛用于医学成像，而钆 已被提议用作顺磁性造影剂， 核磁共振成像。 在本提案中，计划 合成新的能够结合镓的低分子量配体， 铟，钆，在某些情况下，锝具有高稳定性 constants. 配体的结构将被设计成使得两者都 将产生与金属的亲水和亲脂络合物， 也使得可以形成具有正电荷和负电荷的复合物。 新配体与四种金属的稳定常数为 测定并测量与血浆蛋白的交换率。 在这 的平衡和动力学稳定性的方式，这些络合物 将计算配体。 标记化合物的生物分布 最初将在大鼠中测定，在某些情况下，在犬中测定， 灵长类动物 有前途的配体将连接到单克隆抗体上， 用镓、铟或锝标记的单克隆抗体。 然后将这些标记的抗体与抗体在体内进行比较， 使用当前技术标记。 钆配合物将被研究 在体内和体外用作顺磁NMR对比剂 剂. 在这种情况下，由于复合物的宏观量将是 管理，这些复合物的稳定性的详细研究将 贯彻

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.