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.
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.
