Engineered Hydroxamic Acids for Zirconium-89 Positron Emission Tomography (PET) Imaging of Prostate Cancer

正电子发射断层扫描(PET)使用结合在前列腺特异性膜抗原上的锆-89配体复合体来检测和监测前列腺癌。异羟肟酸基配体与锆的结合对铁有很高的亲和力，在体内会引起金属交换和放射性示踪剂的损失。该项目将制备对锆铁具有更高特异性的新配体，并测量免疫-PET成像活性。将制备第二系列大环锆特异性配体，以建立可变的水脂溶解度和药代动力学性质之间的关系。这一结果将提高免疫-PET检测前列腺癌的能力，并改善生存结果。

Positron emission tomography (PET) using a zirconium-89-ligand complex bound to a prostate-specific membrane antigen is used to detect and monitor prostate cancer. The hydroxamic acid-based ligand bound to zirconium has a high affinity towards iron, which can cause metal exchange in vivo and loss of radiotracer. The project will prepare new ligands with a higher specificity towards zirconium over iron, and measure immuno-PET imaging activity. A second series of macrocyclic zirconium-specific ligands will be prepared to establish the relationship between variable water-lipid solubility and pharmacokinetic properties. The results will increase the capability of immuno-PET for prostate cancer detection and improve survival outcomes.