PSMA Theranostics: Current Landscape and Future Outlook

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.

Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives

“…In mRCC patients with high PSMA avidity, another future perspective is represented by Radioligand Therapy. In a theranostic approach, mRCC could be first imaged with PSMA PET/CT and subsequently treated with PSMA labeled with β-emitting (such as 177 Lu or 90 Y) or α-emitting (such as 225 Ac) radionuclides, as it happens today for neuroendocrine tumors and prostate cancer (Zhang et al 2021 ; Uccelli et al 2021 ). This approach could be particularly useful in chrRCC, where PSMA expression is usually high and therapeutic options are limited (Baccala et al 2007 ; Spatz et al 2018 ; Toyama et al 2021 ).…”

Impact of Three-Month Androgen Deprivation Therapy on [68Ga]Ga-PSMA-11 PET/CT Indices in Men with Advanced Prostate Cancer—Results from a Pilot Prospective Study

“…PSMA imaging may theoretically serve as a biomarker for assessing treatment response. However, this application may face significant challenges since PSMA avidity can be affected by several factors (e.g., castration sensitivity, timing and type of therapy, or lesion localization) [ 31 ]. According to the consensus statement on the PSMA PET/CT response criteria, patients with hormone-sensitive prostate cancer should not undergo this imaging modality within the first three months of systemic therapy [ 17 ].…”

Update of PSMA Theranostics in Prostate Cancer: Current Applications and Future Trends

“…Because of its good physical properties and the possibility of post-treatment imaging, 177 Lu labeled PSMA has been extensively studied and it has emerged as a novel treatment for mCRPC. Until recently, the majority of PSMA-targeting tracers involve urea-based agents (small molecule inhibitors) including 177 Lu-PSMA-I&T (imaging and therapy) and 177 Lu-PSMA-617, with the latter being preferred due to lower renal uptake [ 102 , 103 ]. A previous study of Ruigrok et al revealed that although 177 Lu-PSMA-617 and 177 Lu-PSMA-I&T show similar binding characteristics in prostate tumors, 177 Lu PSMA-I&T has a lower tumor-to-kidney ratio than 177 Lu PSMA-617 [ 104 ].…”