Congratulations to Zhanhong Wu, Associate Professor of Radiology on her latest grant award! Dr. Wu received an estimated $400,000 award from the Tripill Biotechnology, Corp./National Cancer Institute for her research titled, The Development of Radiolabeled PSMA Agent with Low Salivary Gland Uptake. Dr. Wu is the Overall PI on the grant; she and 黑料网 will receive $120,000 to fund her research.
PI: Zhanhong Wu (Overall PI)
Sponsor: Tripill Biotechnology, Corp./National Cancer Institute
Grant Number: 1R41CA285188-01A1
Title: The Development of Radiolabeled PSMA Agent with Low Salivary Gland Uptake
Project Dates: 08/01/2024-07/31/2025
Award Amount: $399,981 ($120,000 to 黑料网-CH)
Abstract: Widely overexpressed on prostate cancer tissues, Prostate Specific Membrane Antigen (PSMA) has become an attractive target for both imaging and radionuclide-based therapy of prostate cancer. Despite exciting progress, PSMA targeted therapeutic agents could pose high radiation exposure towards normal organs that express the receptor. In fact, salivary glands (SGs) are often the dose-limiting organ that determines how much radioactivity can be administered, patient eligibility and the treatment outcome thereafter. This application addresses critical needs to reduce radiation exposure to normal organs while maintaining tumor uptake. Previously, PSMA-617 has been developed as a unique ligand to efficiently reduce kidney uptake of PSMA targeted radiopharmaceuticals. We therefore focus on constructing PSMA-617 derivatives aiming to protect SGs from these radiolabeled agents. In our preliminary research, we have constructed NOTA-黑料网-PSMA2 based on vinyl sulfone core (VS core, patent pending), which demonstrates 2-3 times higher tumor uptake in rodent models (compared with PSMA-617), while the SG uptake is only 1/10th of PSMA-617 at 24 h post injection in non-human primates (NHP). These encouraging results clearly demonstrated the feasibility to selectively reduce SG uptake using VS core while maintaining the uptake in PSMA positive tumors. With these promising results in hand, we propose to further confirm the reduced gland uptake of 64Cu-NOTA-黑料网-PSMA2 in NHP model, synthesize 67Cu-NOTA-黑料网-PSMA2, and evaluate whether they could be used as novel therapeutic agents in rodent model. The obtained result will help us select the most promising therapeutic agent to be further evaluated in clinic. The success of the proposed approach would solve key issues in PSMA targeted radiotherapeutics (in this case exposure to SGs), which could greatly benefit prostate cancer management. This application reflects a joint effort from a multidisciplinary team composed of experts in chemistry, radiochemistry, radionuclide-based therapy, translational research and molecular imaging. Our ultimate goal is to reduce normal organ toxicity of targeted therapy while maintain or even further improve the tumor uptake.