Advances in PSMA-Targeted Radionuclide Therapeutics

Abstract

Prostate-specific membrane antigen targeted radionuclide therapies (PSMA-TRT) such as 177Lu-PSMA-617 hold great promise in improving clinical outcomes at various stages of prostate cancer. The FDA approval of 177Lu-PSMA-617 represents a significant advancement in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The VISION trial demonstrated improved radiographic progression-free survival (rPFS) and overall survival (OS) with 177Lu-PSMA-617 in patients with mCRPC who had already receive androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy. Exploration of 177Lu-PSMA-617 in earlier stages of prostate cancer, such as in the PSMAfore trial for patients who have not received chemotherapy, holds great promise for improving long-term outcomes and delaying exposure to chemotherapy. Combining 177Lu-PSMA-617 with other therapies, including chemotherapy, PARP inhibitors, and immunotherapy, is an area of active investigation. This review will also discuss alternative radionuclides (such as actininum-225 and terbium-161) and delivery vehicles (such as PSMA-I&T), which we find promising. Predictive biomarkers and dosimetry will be crucial for identifying patients most likely to benefit from PSMA-TRT. Continued research and refinement of these therapies will lead to PSMA-targeted treatments becoming an integral part of prostate cancer management.

Keywords: 177Lu-PSMA-617; Metastatic castration-resistant prostate cancer (mCRPC); PSMA-targeted therapy; Prostate cancer; Radioligand therapy; Radionuclide therapy.