Radionuclide Therapy in Prostate Cancer: from standalone to combination PSMA theranostics.

Despite significant advances in prostate cancer therapeutic development over the last two decades, metastatic prostate cancer remains a lethal disease. Prostate-specific membrane antigen (PSMA), which is markedly overexpressed by prostate cancer cells, including at metastatic sites, but have low normal tissue expression, has emerged as an important theranostic target for these diseases. Both beta-emitting and alpha-emitting PSMA-targeted radionuclide therapy (RNT) are in clinical development. Several of these agents have already shown promising activity, however, a significant subset of patients have primary resistant disease and secondary resistance invariably occurs. Further, the effect of these therapies on healthy organs limit their therapeutic window. Elucidating the biology of PSMA as well as characterising the pharmacokinetic and pharmacodynamic properties of PSMA-targeted RNT will facilitate therapeutic approaches aimed at improving efficacy and safety. In this review, we provide an overview of existing PSMA-targeting RNT and an update on novel combinatorial approaches.