关键词：抗原；诊断（医学）；膜（生物学）
摘 要：The hypothesis of the original proposal was to discover novel imaging probes for the diagnosis of prostate cancer by targeting simultaneously PSMA and hepsin, which are highly expressed in advanced and metastatic prostate cancer. In Year 3, we successfully established the synthetic strategy for PSMA- hepsin heterobivalent ligands and synthesized two dual-targeting conjugates 12- 13 labeled with optical dye Cy 5.5 and Cy 7, respectively. We also synthesized two peptide-based IPLLVVPL analogs (15,17) linked with DOTA and evaluated their inhibitory activities against hepsin protease. With respect to biological experiments, we developed the PC3/ML cell lines which express PSMA, hepsin, and PSMA/hepsin for in vitro cell uptake and in vivo imaging studies. Compound 13 showed a low but detectable increased cell uptake into the developed cell lines as compared to the control. From these results, we will carry out structural optimization of compound 13 and evaluate their biological activities in vitro and in vivo in Final Year.