About the event
Speaker: Esther Dodson
Group: Cliff Berkman
Title: Development of a ratiometric fluorescence probe for real-time tracking of PSMA-targeted drug delivery
Abstract: Prostate-specific membrane antigen (PSMA) is the hallmark enzyme-biomarker for prostate cancer because it is over-expressed on the cell surface of nearly all prostate cancers. The unique expression of PSMA in prostate cancer has prompted the development of targeted imaging and therapeutic agents. Despite significant advances in creating an array of PSMA-targeting agents, certain key information remains unknown. The long-term goal of this work is to develop a platform for tracking, in real-time, the biodistribution and cargo-release of a pH-responsive PSMA-targeting prodrug by using a near-infrared ratiometric fluorescence imaging probe (NIR-RFP). We hypothesize that a targeted small-molecule diagnostic probe can be developed by harnessing the affinity and cell-penetrating properties of irreversible PSMA inhibitors in consort with a universal pH-responsive cleavable linker. The first aim seeks to determine the fluorescent profile and cargo-release kinetics of our pH-responsive phosphoramidate near-infrared dye module, while the second aim focuses on evaluating the PSMA-NIR-RFP’s biodistribution, uptake, and cargo-release both in vitro and in vivo. Our novel approach is expected to provide a method to estimate the dose of cargo delivered to PSMA(+) tumors for investigators focused on the development of PSMA-targeted drug-conjugates.