Prostate-specific membrane antigen (PSMA)-targeted theranostics have transformed prostate cancer management, but some tumors exhibit low or heterogeneous PSMA expression, limiting eligibility and efficacy for radiopharmaceutical therapy. This review explores emerging biomarkers that may complement or expand beyond PSMA, including gastrin-releasing peptide receptor, fibroblast activation protein, prostate stem cell antigen, CD46, delta-like ligand 3, glypican-3, B7-H3, 6-transmembrane epithelial antigen of the prostate-1, trophoblast cell surface antigen-2, CEACAM5, and vicrostatin. We review their molecular biology, preclinical validation, clinical translation, and ongoing trials. These biomarkers represent diverse biological compartments, broadening the scope of precision radiotheranostics for prostate cancer.
PET clinics. 2026 Apr 07 [Epub ahead of print]
Pedram Heidari, Hossein Jadvar, Bashar Kako, Shadi A Esfahani
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Division of Nuclear Medicine and Molecular Imaging Center, Departments of Radiology, Radiation Oncology and Urology, USC Norris Comprehensive Cancer Center, Keck School of Medicine; Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90033, USA., Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: .