Folate Conjugates for Prostate Cancer Imaging

本项目的目的是设计和评估针对前列腺癌特异性膜抗原(PSMA)的新型叶酸结合物，用于前列腺癌成像。在第一阶段项目期间，具体目标是：1.合成新型叶酸结合物并测定其在体外对前列腺癌细胞的亲和力；初步合成四种叶酸结合物，用99mTc标记，并在培养的前列腺癌细胞中进行评价；2.评价99mTc标记的叶酸结合物在动物模型中的肿瘤定位特性；将在荷人前列腺癌裸鼠体内进行生物分布和药代动力学研究，并与放射性标记的抗PSMA抗体CyT-356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，以确定前列腺癌成像候选对象的进一步临床前开发和临床研究的优点。拟议的商业应用：拟议的项目可能导致开发一种临床上有用的通过闪烁成像进行肿瘤成像的试剂。这为前列腺癌患者的治疗提供了一种快速、灵敏的肿瘤诊断和分期方法，将对前列腺癌患者的治疗产生重大影响。

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.