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2023 Michael & Lori Milken – PCF Young Investigator Award

Breaking Barriers in Prostate Cancer: Novel Clinical Uses of PSMA Radioligand Therapy and Imaging with PSMA PET/CT

James Buteau, MD
The University of Melbourne

Mentors: Michael Hofman, Declan Murphy, Arun Azad

Description:

  • There is a need for improved therapeutic approaches for patients with advanced metastatic castration-resistant prostate cancer (mCRPC), whilst on the other extreme, there is a need to accurately identify clinically significant prostate cancer in individuals presenting with elevated PSA levels or inconclusive MRI results.
  • James Buteau proposes to address both these unmet needs with two first-in-field clinical trials testing PSMA-targeted theranostic approaches.
  • VIOLET is a phase I/II trial that will test a new PSMA-targeted radionuclide therapy, 161-Terbium-PSMA-I&T, in patients with progressive mCRPC. This treatment is similar in concept to the recently approved radionuclide therapy 177-Lutetium-PSMA-617 (Pluvicto®), but uses 161-Terbium instead of 177-Lutetium as the radioactive-emitting isotope. 161-Terbium emits Auger electrons, depositing higher concentrations of radiation to micrometastases, and has shown superior preclinical results in comparison with 177-Lutetium. Dr. Buteau and team will determine the maximum tolerated dose, safety profile and preliminary anti-tumor activity of 161-Terbium-PSMA-I&T.
  • PRIMARY2 is randomized phase III trial that will determine whether the addition of PSMA PET/CT prior to diagnostic prostate biopsy could improve earlier diagnosis of clinically significant prostate cancer, improve biopsy targeting, and help patients without clinically significant prostate cancer to avoid unnecessary biopsies.
  • If successful, this project will benefit two populations of patients by improving survival in men with mCRPC and improving the early diagnosis of prostate cancer when there is a higher chance of cure.

What this means to patients: PSMA-targeted therapy and diagnostic imaging (theranostics) has revolutionized the landscape of prostate cancer in recent years. In this project, Dr. Buteau and team will investigate the potential for new PSMA theranostic applications at both extremes of the disease course. If successful, this project will demonstrate the ability for PSMA PET/CT imaging to specifically detect clinically significantly prostate cancer earlier, while reducing overdiagnosis and overtreatment, as well as determine whether a novel PSMA-targeted radionuclide therapy improves survival in patients with mCRPC.