ldtЛучевая диагностика и терапияDiagnostic radiology and radiotherapy2079-5343Baltic Medical Education Center10.22328/2079-5343-2024-15-4-40-56ldt-1049Research ArticleЛЕКЦИИ И ОБЗОРЫLECTURES AND REVIEWSВозможности радиолигандной терапии рака предстательной железы низкомолекулярными ингибиторами ПСМА, меченными актинием-225: обзорThe possibilities of prostate cancer radioligand therapy with low-molecular-weight PSMA inhibitors labeled with actinium-225: a reviewhttps://orcid.org/0000-0001-8983-5976ТищенкоВ. К.TishchenkoV. K.

Тищенко Виктория Константиновна – доктор биологических наук, заведующий лабораторией экспериментальной ядерной медицины

249036, Калужская область, г. Обнинск, ул. Маршала Жукова, д. 10

Viktoria K. Tishchenko – Dr. of Sci. (Biol.), head of the laboratory of experimental nuclear medicine

249031, 10 Zhukov str., Obninsk, Kaluga region

vikshir82@mail.ruhttps://orcid.org/0000-0001-6655-5592КрыловВ. В.KrylovV. V.

Крылов Валерий Васильевич – доктор медицинских наук, заведующий отделением радиохирургического лечения открытыми радионуклидами

249036, Калужская область, г. Обнинск, ул. Маршала Жукова, д. 10

Valeriy V. Krylov – Dr. of Sci. (Med.), head of the department of radiosurgical treatment with open radionuclides

249031, 10 Zhukov str., Obninsk, Kaluga region 

krylov.mrrc@mail.ruhttps://orcid.org/0000-0002-7809-1059КочетоваТ. Ю.KochetovaT. Yu.

Кочетова Татьяна Юрьевна – старший научный сотрудник отделения радиохирургического лечения открытыми радионуклидами

249036, Калужская область, г. Обнинск, ул. Маршала Жукова, д. 10

Tatiana Yu. Kochetova – senior researcher of the department of radiosurgical treatment with open radionuclides

249031, 10 Zhukov str., Obninsk, Kaluga region 

tat_mail@inbox.ruhttps://orcid.org/0000-0003-4934-2012ШуриновА. Ю.ShurinovA. Yu.

Шуринов Андрей Юрьевич – кандидат медицинских наук, старший научный сотрудник отделения радиохирургического лечения открытыми радионуклидами

249036, Калужская область, г. Обнинск, ул. МаршалаЖукова, д. 10

Andrey Yu. Shurinov – Cand. of Sci. (Med.), senior researcher of the department of radiosurgical treatment with open radionuclides

249031, 10 Zhukov str., Obninsk, Kaluga region 

shurinov@mail.ruhttps://orcid.org/0000-0001-5170-9595ВласоваО. П.VlasovaO. P.

Власова Оксана Петровна – кандидат биологических наук, ведущий научный сотрудник лаборатории экспериментальной ядерной медицины; заместитель заведующего отделом сопровождения грантов и внешних контрактов Центра инновационных радиологических и регенеративных технологий федерального государственного бюджетного учреждения; ведущий научный сотрудник лаборатории экспериментальной ядерной медицины 

249036, Калужская область, г. Обнинск, ул. Королева, д. 4;

249036, Калужская область, г. Обнинск, ул. Маршала Жукова, д. 10

Oksana P. Vlasova – Cand. of Sci. (Biol.), leading researcher of the laboratory of experimental nuclear medicine; deputy of the head of grants and external contracts department of the centre of innovative radiological and regenerative technologies

249031, 10 Zhukov str., Obninsk, Kaluga region;

249036, 4 Korolyova str., Obninsk, Kaluga region

somina@inbox.ruhttps://orcid.org/0000-0001-8901-4596ШегайП. В.ShegaiP. V.

Шегай Петр Викторович – кандидат медицинских наук, заведующий Центром инновационных радиологических и регенеративных технологий федерального государственного бюджетного учреждения

249036, Калужская область, г. Обнинск, ул. Королева, д. 4

Petr V. Shegaj – Cand. of Sci. (Med.), head of the centre of innovative radiological and regenerative technologies

249036, 4 Korolyova str., Obninsk, Kaluga region

dr.shegai@mail.ruhttps://orcid.org/0000-0001-7689-6032ИвановС. А.IvanovS. A.

Иванов Сергей Анатольевич – доктор медицинских наук, профессор, член-корреспондент РАН, директор

249036, Калужская область, г. Обнинск, ул. Маршала Жукова, д. 10

Sergey A. Ivanov – Dr. of Sci. (Med.), professor, corresponding member of the Russian Academy of Sciences, director

249031, 10 Zhukov str., Obninsk, Kaluga region 

oncourolog@gmail.comhttps://orcid.org/0000-0001-8784-8415КапринА. Д.KaprinA. D.

Каприн Андрей Дмитриевич – доктор медицинских наук, профессор, академик РАН, генеральный директор; заведующий кафедрой урологии и оперативной нефрологии с курсом онкоурологии 

249036, Калужская область, г. Обнинск, ул. Королева, д. 4;

117198, Москва, ул. Миклухо-Маклая, д. 6

Andrey D. Kaprin – Dr. of Sci. (Med.), professor, Academician of the Russian Academy of Sciences, general director; head of the department of urology and operative nephrology with a course of oncourology

249036, 4 Korolyova str., Obninsk, Kaluga region;

117198, 6 Miklukho-Maklaya str., Moscow

kaprin@mail.ruМедицинский радиологический научный центр имени А. Ф. ЦыбаРоссияA. Tsyb Medical Radiological Research CentreRussian FederationМедицинский радиологический научный центр имени А. Ф. Цыба; Национальный медицинский исследовательский центр радиологииРоссияA. Tsyb Medical Radiological Research Centre; National Medical Research Radiological CentreRussian FederationМедицинский радиологический научный центр имени А. Ф. Цыба; Российский университет дружбы народовРоссияA. Tsyb Medical Radiological Research Centre; Рeoples Friendship University of Russia (RUDN University)Russian FederationНациональный медицинский исследовательский центр радиологии; Российский университет дружбы народов; Московский научно-исследовательский онкологический институт имени П. А. ГерценаРоссияNational Medical Research Radiological Centre; Рeoples Friendship University of Russia (RUDN University); P. Hertsen Moscow Oncology Research InstituteRussian Federation2024280120251544056Copyright © Тищенко В.К., Крылов В.В., Кочетова Т.Ю., Шуринов А.Ю., Власова О.П., Шегай П.В., Иванов С.А., Каприн А.Д., 20252025Тищенко В.К., Крылов В.В., Кочетова Т.Ю., Шуринов А.Ю., Власова О.П., Шегай П.В., Иванов С.А., Каприн А.Д.Tishchenko V.K., Krylov V.V., Kochetova T.Y., Shurinov A.Y., Vlasova O.P., Shegai P.V., Ivanov S.A., Kaprin A.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://radiag.bmoc-spb.ru/jour/article/view/1049ВВЕДЕНИЕ

ВВЕДЕНИЕ: Терминальная форма рака предстательной железы, известная как метастатический кастрат-резистентный рак предстательной железы (мКРРПЖ), представляет собой прогрессирующее заболевание с ограниченными терапевтическими возможностями и неблагоприятным прогнозом выживаемости. Существует высокая потребность в более эффективных (таргетных) стратегиях системной терапии. Радиолигандная терапия (РЛТ) дает возможность лечить мКРРПЖ специфическим и опухолеселективным способом, воздействуя на простат-специфический мембранный антиген (ПСМА), сверх-экспрессируемый опухолевыми клетками предстательной железы.

ЦЕЛЬ

ЦЕЛЬ: Анализ эффективности и безопасности РЛТ мКРРПЖ с использованием низкомолекулярных ПСМА-ингибиторов, меченных альфа-излучающим радионуклидом 225Ас, по данным литературы.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ: Поиск литературы выполнялся в период с 01.04.2024 по 27.04.2024 на русском и английском языках в базах данных Medline/PubMed, Google Scholar, РИНЦ/elibrary по следующим ключевым словам: актиний-225 (actinium 225, 225Ac), ПСМА (PSMA), 225Ас-ПСМА (225Ac-PSMA), радиолигандная терапия рака предстательной железы (radioligand therapy of prostate cancer).

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ: В обзоре представлен современный мировой опыт РЛТ мКРРПЖ с применением низкомолекулярных ингибиторов ПСМА, меченных альфа-излучающим радионуклидом 225Ac. Представлены данные об эффективности РЛТ с использованием 225Aс-ПСМА-617 и 225Aс-ПСМА-I&T, а также результаты тандемной терапии. Подробно обсуждаются токсические эффекты этого лечения, рассматриваются способы их предотвращения или снижения интенсивности.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ: РЛТ с 225Ac-ПСМА – эффективная и безопасная терапевтическая стратегия против мКРРПЖ, включая опухоли, резистентные к традиционным методам лечения, а также в случае неэффективности РЛТ с 177Lu-ПСМА. Более чем у половины пролеченных пациентов уровень ПСА снижался более чем на 50%. Наиболее часто встречаемым осложнением РЛТ является ксеростомия.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ: РЛТ с ПСМА-специфичными лигандами, меченными 225Ас, является многообещающим методом терапии пациентов с мКРРПЖ, исчерпавших все возможные варианты противоопухолевой терапии.

INTRODUCTION

INTRODUCTION: The terminal form of prostate cancer known as metastatic castrate-resistant prostate cancer (mCRPC) is a progressive disease with limited therapeutic options and poor survival prognosis. Therefore, there is a high demand for more effective (targeted) strategies of systemic therapy. Radioligand therapy (RLT) offers the possibility to treat mCRPC in a specific and tumor-selective manner by targeting prostate-specific membrane antigen (PSMA), which is overexpressed by prostate tumor cells.

OBJECTIVE

OBJECTIVE: To analyze the efficacy and safety of RLT of mCRPC using low molecular weight PSMA inhibitors labeled with alpha-emitting radionuclide 225Ac based on the literature data.

MATERIALS AND METHODS

MATERIALS AND METHODS: Literature search was performed during a period of 01.04.2024 to 27.04.2024 in Russian and English language in databases Medline/PubMed, Google Scholar, RINC/Elibrary using the following keywords: actinium-225 (225Ac), PSMA, 225Ac-PSMA, radioligand therapy of prostate cancer.

RESULTS

RESULTS: This review presents the current worldwide experience of mCRPC RLT using low-molecular-weight PSMA inhibitors labeled with the alpha-emitting radionuclide 225Ac. Data on the efficacy of RLT with 225Aс-PSMA-617 and 225Aс-PSMA-I&T as well as the results of tandem therapy are presented. The toxicity of this treatment is discussed in detail, and ways of their avoidance or reduction their intensity are reviewed.

DISCUSSION

DISCUSSION: RLT with 225Ac-PSMA ligands is an effective and safe strategy for mCRPC therapy, including tumors, which are resistant to conventional therapies, and also in case of inefficacy of RLT with 177Lu-PSMA. More than a half of treated patients had PSA levels declined greater than 50%. The most common complication of RLT is xerostomia.

CONCLUSION

CONCLUSION: RLT with 225Ac-labeled PSMA-specific ligands is a promising therapy for patients with mCRPC, who have exhausted all possible antitumor therapies.

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The authors declare that there are no conflicts of interest present.