RADIONUCLIDE DIAGNOSIS OF PROSTATE CANCER: POSITRON EMISSION TOMOGRAPHY WITH 68GA-PSMA INHIBITORS AND THEIR PHARMACEUTICAL DEVELOPMENT
Rubrics: REVIEW
Authors:
1.
Moscow, Russian Federation
2.
Russian Federation
Type:
Article
Pages:
from 58
to 74
Status:
Published
Received:
04.12.2017
Accepted:
05.12.2017
Published:
05.12.2017
Subject area:
UDK 61 Медицина. Охрана здоровья
GRNTI 34.45 Фармакология
GRNTI 34.49 Радиационная биология
GRNTI 34.45 Фармакология
GRNTI 34.49 Радиационная биология
Language:
Russian, English
Keywords:
PET, 68Ga, radiopharmaceuticals, PSMA, prostate cancer
Abstract (English):
This review is devoted to the synthesis of the main and most relevant data on the development and clinical use of radiopharmaceuticals (RPs) based on PSMA-inhibitors labeled with 68Ga for the diagnosis of prostate cancer (PC). The generator method of 68Ga production, which ensures the wide availability of this radionuclide for medical organizations, is the reason for the permanent interest to the RPs based on 68Ga. The development of RPs based on inhibitors of the prostate-specific membrane antigen became the second wave of global excitement about 68Ga-RPs, after labeled derivates of the ocreotide for the diagnosis of neuroendocrine tumors. PC is one of the most urgent problems of modern oncology. The place of prostate cancer in the structure of the oncological morbidity of the male population, as well as the significance of radionuclide diagnostics in the clinical staging of the disease and the strategy of therapy are considered. Data on the structure and properties of the prostate-specific membrane antigen (PSMA), its role in the body and expression in the foci of pathological processes are presented. Known PSMA inhibitors and the dependence of their properties on structure are considered. The main part of the review is devoted to the key results of the pharmaceutical development of RPs based on PSMA-inhibitors labeled with 68Ga. The effect of the fragments (ligand, linker and chelator) on the final radiopharmaceutical molecule on the pharmacokinetics is considered. The review also includes data on the clinical efficacy of PET with 68Ga-PSMA in the diagnosis of PC. Data on the availability of 68Ga-RPs in Russia today, as well as references to regulatory documents that allow the use of such RPs, are presented. In conclusion, a brief summary of the literature data and conclusions on the most promising radiopharmaceuticals for the diagnosis and therapy of prostate cancer and further perspectives are presented.
This review is devoted to the synthesis of the main and most relevant data on the development and clinical use of radiopharmaceuticals (RPs) based on PSMA-inhibitors labeled with 68Ga for the diagnosis of prostate cancer (PC). The generator method of 68Ga production, which ensures the wide availability of this radionuclide for medical organizations, is the reason for the permanent interest to the RPs based on 68Ga. The development of RPs based on inhibitors of the prostate-specific membrane antigen became the second wave of global excitement about 68Ga-RPs, after labeled derivates of the ocreotide for the diagnosis of neuroendocrine tumors. PC is one of the most urgent problems of modern oncology. The place of prostate cancer in the structure of the oncological morbidity of the male population, as well as the significance of radionuclide diagnostics in the clinical staging of the disease and the strategy of therapy are considered. Data on the structure and properties of the prostate-specific membrane antigen (PSMA), its role in the body and expression in the foci of pathological processes are presented. Known PSMA inhibitors and the dependence of their properties on structure are considered. The main part of the review is devoted to the key results of the pharmaceutical development of RPs based on PSMA-inhibitors labeled with 68Ga. The effect of the fragments (ligand, linker and chelator) on the final radiopharmaceutical molecule on the pharmacokinetics is considered. The review also includes data on the clinical efficacy of PET with 68Ga-PSMA in the diagnosis of PC. Data on the availability of 68Ga-RPs in Russia today, as well as references to regulatory documents that allow the use of such RPs, are presented. In conclusion, a brief summary of the literature data and conclusions on the most promising radiopharmaceuticals for the diagnosis and therapy of prostate cancer and further perspectives are presented.
Keywords:
PET, 68Ga, radiopharmaceuticals, PSMA, prostate cancer
PET, 68Ga, radiopharmaceuticals, PSMA, prostate cancer
Преимущества методов ядерной медицины обусловили её устойчивое развитие на протяжении нескольких последних десятилетий и превращение в неотъемлемую часть клинической практики в развитых странах. Активное внедрение метода позитронно-эмиссионной томографии (ПЭТ) в медицинских учреждениях вместе с постоянно разрабатываемыми новыми радиофармацевтическими препаратами (РФП) позволило поднять на новый уровень диагностические и терапевтические возможности для ряда самых разнообразных социально значимых заболеваний. Общепризнано, что с начала широкого применения ПЭТ в онкологии прогноз выживаемости пациентов увеличился по меньшей мере в два раза.
