Prostate Cancer, Part 2: PSMA and Beyond

Ac-PSMA exploit high linear energy transfer and short path length to treat micrometastatic and radioresistant disease, including post-β-therapy progression, but are constrained by toxicity risk, daughter redistribution, complex dosimetry, and limited radionuclide supply. Emerging radionuclides and ligand-engineering approaches are discussed as routes to improve tumor retention, enable true theranostic pairing, and expand global feasibility. The next wave of strategies that broaden molecular coverage beyond PSMA alone, including gastrin-releasing peptide receptor- and fibroblast activation protein-targeted agents and dual-target heterodimers, designed to address inter- and intrapatient heterogeneity and PSMA-insufficient disease, are also outlined. These advances shift prostate cancer theranostics from a single-target paradigm toward a more nuanced ecosystem requiring rational selection, sequencing, and personalization of radioligand choice across the disease continuum.