[PSMA-targeted therapy in the treatment of metastatic castration-resistant prostate cancer]

Metastatic castration-resistant prostate cancer (mCRPC) is the most severe form of prostate cancer, developing in about 30% of patients; standard approaches of its treatment often remain ineffective. The development of theranostics principle and the discovery of the prostate-specific membrane antigen (PSMA) make it possible to implement a new approach in the treatment of patients with mCRPC - PSMA-targeted therapy. It is based on the use of a specific radionuclide (alpha or beta-minus emitter) associated with a ligand (radioligand) that binds to PSMA and has a targeted effect on tumor cells. One of the advantages of this technique in mCRPC is simultaneous diagnostics and treatment of the disease (the basic principle of the theranostics). The high specificity of PSMA-targeted therapy in combination with increased expression of PSMA by cancer cells allows to treat numerous distant metastases, slowing down the progression of the disease and improving the patients condition.

Review of the main approaches to the use of PSMA and radionuclides to treat patients with mCRPC as part of PSMA-targeted therapy.

The most preferred method to treat patients with mCRPC is --radionuclide therapy, since --radiation isotopes have a "crossfire effect" and relatively low toxicity and are available for use. The most optimal radionuclide from the group of -emitters is lutetium-177 - 177Lu (PSMA radioligands: 177Lu-PSMA-617 and 177Lu-PSMA-I&T). Despite the large number of --radionuclide therapy advantages, it is also possible to use -radionuclide therapy; actinium-225-225Ac (PSMA radioligand: 225Ac-PSMA) therapy is more toxic to the body, however, it can be considered as a second line or escape medication for patients with mCRPC and previous ineffective --therapy.