A Review of 177Lutetium-PSMA and 225Actinium-PSMA as Emerging Theranostic Agents in Prostate Cancer

The development of prostate-specific membrane antigen (PSMA) ligands labeled with radionuclides is a ground-breaking achievement in the management of prostate cancer. With the increasing use of (68)Gallium-PSMA and F-18-DCFPyL (Pylarify) and their approval by the Food and Drug Administration (FDA), other PSMA agents and their unique characteristics are also being studied. Two other PSMA agents, namely (177)Lutetium- PSMA (Lu-177-PSMA) and (225)Actinium- PSMA (Ac-225-PSMA), are currently drawing the researcher's attention mainly due to their theranostic importance. Studies focusing on the essential characteristics of these two emerging radiotracers are relatively lacking. Hence, this review article, beginning with a brief introduction, intends to provide insights on the mechanism, efficacy, adverse effects, usefulness, including theranostic implications, and limitations of these two emerging PSMA agents. The Lu-177-PSMA is commercially accessible, is well tolerated, and has been found to lower prostate-specific antigen (PSA) levels while improving patients' quality of life. It also reduces pain and the requirement for analgesics and is safe for advanced diseases. However, despite its potential advantages, around one-third of patients do not respond satisfactorily to this costly treatment; it is still challenging to personalize this therapy and predict its outcome. Similarly, Ac-225 is compatible with antibody-based targeting vectors, releasing four extremely hazardous high-energy emissions with a longer half-life of 10 days. It has made Ac-225-PSMA therapy useful for tumors resistant to standard treatments, with a better response than Lu-177-PSMA. Dosimetry studies show a good biochemical response without toxicity in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). However, it can potentially cause significant damage to healthy tissues if not retained at the tumor site. Encapsulating radionuclides in a nano-carrier, hastening the absorption by tumor cells, and local delivery might all help reduce the harmful consequences. Both have advantages and disadvantages. The choice of PSMA agents may rely on desired qualities, cost, and convenience, among other factors. Further research is warranted in order to better understand their ideal use in clinical settings.