> Our Work > The Work We Fund

2023 Tom Murphy – PCF Young Investigator Award

A Rapid Molecular Imaging Diagnostic for Neuroendocrine Prostate Cancer

David Wise, MD, PhD

Mentors: Shohei Koide, J.T. Poirier

Description:

  • Androgen receptor signaling inhibitors (ARSIs) have revolutionized treatment of metastatic castration resistant prostate cancer (mCRPC) patients by significantly extending their survival and improving their quality of life. However, 10-20% of these patients will eventually develop neuroendocrine prostate cancer (NEPC), a highly aggressive mCRPC subtype that is resistant to all current treatments.
  • NEPC expresses low/no levels of PSMA, and therefore cannot be imaged with PSMA PET, which is the current gold standard for imaging prostate cancer. The current approach to diagnosing NEPC lesions is limited to biopsies, which are not always feasible and carry inherent risk. There is an urgent need to develop non-invasive diagnostics for NEPC and novel NEPC-directed treatment approaches to improve outcomes in these patients.
  • Neuroendocrine cancers have previously been shown to express delta-like ligand 3 (DLL3), a cell surface protein that can be detected with antibody-based imaging agents.
  • In this project, Dr. Wise and team will develop a novel monobody-based DLL3-targeted PET imaging probe for identifying the presence of NEPC lesions.
  • Monobody scaffolds, invented by the Koide Lab at NYU, because of their small size have more favorable kinetic features that lead to improvements in imaging performance.
  • The team will conduct a phase 1 trial to evaluate the safety, feasibility, and performance of the DLL3-targeted PET agent in patients with NEPC.
  • If successful, this project will result in a new PET imaging agent to diagnose the presence of NEPC in patients with advanced prostate cancer.

What this means to patients: NEPC is a highly aggressive, untreatable form of advanced prostate cancer, for which both diagnostic agents and new treatments are urgently needed. Dr. Wise and team will develop and clinically validate a new DLL3-targeted monobody-based PET imaging agent for the diagnosis of NEPC in patients. This will enable clinicians to more easily identify patients with NEPC, and help to guide treatment decisions in these patients.