The potential of PSMA-targeted alpha therapy in the management of prostate cancer

Introduction: Alpha emitters present several advantages for cancer therapy. The radiopharmaceutical 223Ra-dichloride has been recently introduced for the targeted alpha therapy (TAT) of metastastic castration-resistant prostate cancer (mCRPC). However, since 223Ra-dichloride targets only skeletal lesions, its use in clinical practice is recommended only in subjects without visceral metastases. To overcome this, several efforts have been made to develop radiopharmaceuticals suitable for TAT and specifically directed toward the biomarker prostate specific membrane antigen (PSMA), overexpressed by both skeletal and visceral metastases from mCRPC. Areas covered: The radiobiological principles concerning TAT applications are covered, with particular emphasis on its pros and cons, especially in comparison with beta-emitter radionuclide therapy. Furthermore, the role of PSMA as a theranostic target for imaging and therapy is reviewed. Lastly, the pre-clinical and clinical applications of TAT through 225Actinium (225AC) and 213Bismuth (213Bi) are discussed. Expert opinion: PSMA-based TAT holds the promise of becoming a powerful tool for the management of mCRPC. Nevertheless, several issues have still to be addressed, especially concerning TAT toxicity. Furthermore, several efforts have to be made for identifying the more adequate alpha-emitter (225Ac vs 213Bi) with a view to the patient’s tailored therapeutic approach.