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2023 Jeff & Loyd Zisk – PCF Young Investigator

Conditionally Activated Membrane Binding Probes for Improved Targeted Radiotherapy in Metastatic Castration Resistant Prostate Cancer

Apurva Pandey, PhD
University of California, San Francisco (UCSF)

Mentors: Michael Evans, Charles Craik, Felix Feng

Description:

  • Radioligand therapy (RLT) is a new class of treatments that consist of a tumor-targeting molecule attached to a radioactive isotope, that deliver cell-killing radiation directly to tumor cells. The same tumor-targeting molecules can also be attached to less powerful isotopes that enable tumor imaging with PET machines. The pairing of therapeutic + diagnostic agents (“theranostics”) allows clinicians to determine if patients’ tumors express the target, and aids in optimal matching of patients with treatments.
  • Pluvicto (177Lu-PSMA-617) is a PSMA-targeted RLT that recently received FDA approval for treatment of metastatic castration-resistant prostate cancer (mCRPC). However, several factors limit the efficacy of PSMA-targeted RLTs, and improved RLT strategies are needed to cure patients with advanced prostate cancer.
  • Dr. Apurva Pandey and team are developing a new class of RLTs called “restricted interaction peptides” (RIPs). RIPs are small protein fragments attached to radioactive isotopes, that have a unique chemistry which allows them to emit radiation only once inside tumor cells.
  • In this project, Dr. Pandey and team will develop and test the first RIPs that target a tumor associated protease specifically and highly expressed by prostate cancer cells, making it a promising therapeutic target.
  • This project will develop and optimize these tumor targeted RIPs for both prostate cancer imaging and therapy. They will test preclinical anti-tumor efficacy, biodistribution, and investigate the mechanism of action of targeted RIPs in preclinical prostate cancer models.
  • If successful, this project will develop a new class of theranostic agents for prostate cancer, that are both safer and more effective than PSMA-targeted RLT.

What this means to patients: 177Lu-PSMA-617 is a highly promising new radioligand therapy for patients with mCRPC, but unfortunately, it is not curative. Dr. Pandey and team will develop a new RLT and accompanying molecular imaging agent specific to prostate cancer, which uses a novel chemistry approach in which the agent becomes activated only upon entering tumor cells. This approach may lead to a more effective and safer treatment for prostate cancer, thus improving both the length and quality of life for patients.