PSMA Theranostics: Current Landscape and Future Outlook

SIMPLE SUMMARY: The prognosis for metastatic prostate cancer patients remains poor. Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer and is a promising target for both imaging and therapy. In this review paper, we provide an overview of the evidence for PSMA-targeted imaging in prostate cancer, focusing on different imaging modalities and their theranostic applications. We will also review PSMA-targeted radioligand therapy, focusing on lutetium-177 radioligand therapy and alpha-emitting radioligand therapy with actinium-225. Combination regimens with lutetium-177 and other systemic therapy agents will be reviewed. Antibody-based radioimmunotherapy will also be discussed along with other noteworthy radionuclide agents. ABSTRACT: Introduction: Prostate-specific membrane antigen (PSMA) is a promising novel molecular target for imaging diagnostics and therapeutics (theranostics). There has been a growing body of evidence supporting PSMA theranostics approaches in optimizing the management of prostate cancer and potentially altering its natural history. Methods: We utilized PubMed and Google Scholar for published studies, and clinicaltrials.gov for planned, ongoing, and completed clinical trials in PSMA theranostics as of June 2021. We presented evolving evidence for various PSMA-targeted radiopharmaceutical agents in the treatment paradigm for prostate cancer, as well as combination treatment strategies with other targeted therapy and immunotherapy. We highlighted the emerging evidence of PSMA and fluorodeoxyglucose (FDG) PET/CT as a predictive biomarker for PSMA radioligand therapy. We identified seven ongoing clinical trials in oligometastatic-directed therapy using PSMA PET imaging. We also presented a schematic overview of 17 key PSMA theranostic clinical trials throughout the various stages of prostate cancer. Conclusions: In this review, we presented the contemporary and future landscape of theranostic applications in prostate cancer with a focus on PSMA ligands. As PSMA theranostics will soon become the standard of care for the management of prostate cancer, we underscore the importance of integrating nuclear medicine physicians into the multidisciplinary team.