Accession Number:

ADA592601

Title:

Hetero-bivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

Descriptive Note:

Annual rept. 1 Apr 2012-31 Aug 2013

Corporate Author:

SEJONG UNIV SEOUL (KOREA)

Personal Author(s):

Report Date:

2013-09-01

Pagination or Media Count:

13.0

Abstract:

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 PC3ML cell lines which express PSMA, hepsin, and PSMAhepsin 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.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE