How to cite: Gamie, Sherief H. “Radiology & Theranostics in Castrate Resistant Prostate Cancer (CRPC).” November 2025. Accessed Dec 2025. https://grandroundsinurology.com/radiology-theranostics-in-castrate-resistant-prostate-cancer-crpc/
Sherief H. Gamie, MD, PhD, Chief & Director, Molecular Imaging and Theranostics, Professor of Clinical Radiology, UC San Diego Health, San Diego, California, reviews the evolution of radiology and theranostics in the management of metastatic castration-resistant prostate cancer (mCRPC). He begins by clarifying guideline-based definitions of castration resistance, which include disease progression, clinical, radiographic, or biochemical, despite serum testosterone below 50 ng/dL. Both NCCN and European guidelines align closely, distinguishing between biochemical and radiologic progression.
Dr. Gamie then details the biologic and diagnostic importance of PSMA expression. Nearly 100 percent of normal prostate tissue expresses PSMA, and over 95 percent of prostate tumors maintain expression, with even higher rates in metastatic lesions. High PSMA expression on preoperative biopsy correlates with significantly improved recurrence-free survival, demonstrating its prognostic value.
He traces the development of PSMA imaging from early prostascint scans with indium-111–labeled antibodies to modern PET-based radiopharmaceuticals. Early tracers such as C-11 and F-18 choline evolved into F-18 PSMA agents with superior spatial resolution and lower physiologic urinary activity. The introduction of hybrid PET/CT and PET/MRI enables simultaneous molecular and anatomic localization, enhancing accuracy for staging, restaging, and treatment response assessment.
Dr. Gamie highlights theranostics as the merging of diagnostic and therapeutic functions using the same molecular target. Radioligand therapies such as lutetium-177–PSMA deliver targeted beta radiation to metastatic lesions, improving imaging-based progression-free survival from approximately 3.4 to 8.7 months in clinical studies. He also notes alpha-emitting alternatives such as radium-223 and actinium-225 under active investigation.
PSMA PET/CT thus serves diagnostic, therapeutic, and prognostic roles across the prostate cancer continuum, from initial staging through radioligand therapy response assessment, positioning theranostics as a transformative modality in advanced urologic oncology.
ABOUT THE AUTHOR
Dr. Sherief H. Gamie, MD, PhD, is a Professor of Clinical Radiology and the Chief & Director Molecular Imaging and Theranosticsat the University of California, San Diego, and is affiliated with multiple hospitals in the area. Dr. Gamie’s clinical interests include targeted applications of radiopharmaceuticals in cancer diagnosis and therapy.
