Shapovalenko R A, Shpikina A D, Morozov A O, Gazimiev M A, Enikeev D V
I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
Urologiia. 2024 May(2):75-82.
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.
转移性去势抵抗性前列腺癌（mCRPC）是前列腺癌最严重的形式，约30%的患者会发展为此病；其标准治疗方法往往仍然无效。治疗诊断学原理的发展以及前列腺特异性膜抗原（PSMA）的发现，使得在mCRPC患者的治疗中能够实施一种新方法——PSMA靶向治疗。它基于使用与配体（放射性配体）结合的特定放射性核素（α或β-发射体），该配体与PSMA结合并对肿瘤细胞具有靶向作用。这种技术在mCRPC中的优势之一是疾病的同步诊断和治疗（治疗诊断学的基本原理）。PSMA靶向治疗的高特异性与癌细胞中PSMA表达增加相结合，能够治疗众多远处转移灶，减缓疾病进展并改善患者状况。
综述作为PSMA靶向治疗一部分使用PSMA和放射性核素治疗mCRPC患者的主要方法。
治疗mCRPC患者的最优选方法是——放射性核素治疗，因为——辐射同位素具有“交叉火力效应”且毒性相对较低且可供使用。发射体组中最理想的放射性核素是镥-177 - 177Lu（PSMA放射性配体：177Lu-PSMA-617和177Lu-PSMA-I&T）。尽管——放射性核素治疗有诸多优势，但也可以使用——放射性核素治疗；锕-225-225Ac（PSMA放射性配体：225Ac-PSMA）治疗对身体毒性更大，然而，它可被视为mCRPC患者和先前无效——治疗患者的二线或补救药物。
