Abstract
BACKGROUND: Prostate cancer (PCa) remains one of the most commonly diagnosed malignancies and a leading cause of cancer-related morbidity and mortality among men worldwide. Despite considerable progress in diagnostic and therapeutic modalities, conventional approaches often fall short in capturing disease heterogeneity and managing advanced or treatment-resistant cases. Over the past years, molecular imaging and targeted radionuclide therapy within a theranostic framework have emerged as powerful tools to potentially overcome these limitations. In this context, copper radioisotopes-particularly copper-61 (T(1/2) = 3.33 h; 61% β(+)), copper-64 (T(1/2) = 12.7 h; 17% β(+), 39% β(-)), and copper-67 (T(1/2) = 2.58 d; 100% β(-))-have garnered considerable attention due to their favorable half-lives, straightforward coordination chemistry, and optimal physical decay properties for both imaging and therapy. MAIN BODY: This review comprehensively examines the progress and prospects of copper-based radiopharmaceuticals for PCa theranostics, with particular emphasis on agents targeting prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR), the two most extensively studied and clinically relevant molecular targets in this setting. Alternative markers are also discussed as promising avenues to tackle disease heterogeneity and expand the clinical applicability of these conjugates. By consolidating preclinical and clinical evidence, we aim to identify current challenges and opportunities in the development of copper-based radiopharmaceuticals, and contribute to a paradigm shift toward the widespread clinical adoption of these novel radiopharmaceutical platforms for improved patient care. CONCLUSION: Copper-based radiopharmaceuticals represent a promising class of agents with the potential to refine PCa management. As research advances, these compounds are poised to enhance diagnostic precision and therapeutic efficacy, paving the way for more personalized strategies and favorable clinical outcomes.