Folate Conjugates for Prostate Cancer Imaging

本项目的目的是设计和评估针对前列腺特异性膜抗原（PSMA）的新型叶酸偶联物用于前列腺癌成像。在一期项目期间，具体目标是：1。合成新型叶酸偶联物并测定其体外对前列腺癌细胞的亲和力首先将合成一系列四种叶酸缀合物，用99mTc标记，并在培养的前列腺癌细胞中进行评估；2. 在动物模型上评价99mtc标记叶酸偶联物的肿瘤定位特性；将在携带人类前列腺癌异种移植物的胸腺小鼠中进行生物分布和药代动力学研究，并将结果与放射性标记的CYT-356（一种针对PSMA的改性抗体）获得的结果进行比较。该项目的成功完成将为我们提供必要的数据，以确定所选候选前列腺癌成像的进一步临床前开发和临床研究的优点。拟议的商业应用：拟议的项目可能会导致一种临床有用的药物的发展，通过闪烁成像肿瘤。这将通过提供一种快速和高度敏感的肿瘤诊断和分期方法，对前列腺癌患者的管理产生重大影响。

The objective of this project is to design and evaluate novel folate conjugates targeted to the prostate-specific membrane antigen (PSMA) for prostate cancer imaging. In the Phase I project period, the Specific Aims are: 1. To synthesize novel folate conjugates and determine their affinity for prostate cancer cells in vitro; a series of four folate conjugates will initially be synthesized, labeled with 99mTc and evaluated in cultured prostate cancer cells; 2. To evaluate the tumor localizing properties of the 99mTc-labeled folate conjugates in animal models; biodistribution and pharmacokinetic studies will be carried out in athymic mice carrying human prostate cancer xenografts and the results compared with those obtained with radiolabeled CYT-356, a modified antibody against the PSMA. Successful completion of this project should provide us with the necessary data to determine the merit of further preclinical development and clinical studies of the selected candidate for prostate cancer imaging. PROPOSED COMMERCIAL APPLICATIONS: The proposed project could lead to the development of a clinically useful agent for tumor imaging by scintigraphy. This will have a significant impact on the management of prostate cancer patients by providing a rapid and highly sensitive method of tumor diagnosis and staging.