oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2024-23-4-162-171oncotomsk-3202Research ArticleОБЗОРЫREVIEWSСпособы уменьшения накопления радиоактивности в почках при таргетной терапии с использованием малых молекул, пептидов и фрагментов антителWays to reduce radioactivity accumulation in the kidney during targeted therapy using small molecules, peptides and antibody fragmentshttps://orcid.org/0000-0003-3001-5855АвровК. О.AvrovK. O.

Авров Кирилл Олегович, кандидат биологических наук, старший научный сотрудник лаборатории гибридомной технологии

Researcher ID (WOS): ABE-4959-2020

197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 70

Kirill O. Avrov, PhD, Senior Researcher, Laboratory of Hybridoma Technology

Researcher ID (WOS): ABE-4959-2020

70, Leningradskaya St., Saint Petersburg, Pesochny village, 197758

kirillavrov@hotmail.comhttps://orcid.org/0000-0002-1718-9335ШатикС. В.ShatikS. V.

Шатик Сергей Васильевич, кандидат биологических наук, заведующий отделением циклотронных радиофармпрепаратов

Researcher ID (WOS): ABB-4584-2021

197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 70

Sergey V. Shatik, PhD, Head of the Department of Cyclotron Radiopharmaceuticals

Researcher ID (WOS): ABB-4584-2021

70, Leningradskaya St., Saint Petersburg, Pesochny village, 197758

https://orcid.org/0000-0002-0957-8453СамойловичМ. П.SamoilovichM. P.

Самойлович Марина Платоновна, доктор биологических наук, главный научный сотрудник лаборатории гибридомной технологии

Researcher ID (WOS): A-1517-2017

197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 70

Marina P. Samoilovich, DSc, Chief Researcher, Laboratory of Hybridoma Technology

70, Leningradskaya St., Saint Petersburg, Pesochny village, 197758

ФГБУ «Российский научный центр радиологии и хирургических технологий им. акад. А.М. Гранова» Минздрава РоссииРоссияA.M. Granov Russian Research Center of Radiology and Surgical Technologies of the Ministry of Health of RussiaRussian Federation202409092024234162171Copyright © Авров К.О., Шатик С.В., Самойлович М.П., 20242024Авров К.О., Шатик С.В., Самойлович М.П.Avrov K.O., Shatik S.V., Samoilovich M.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/3202

Введение фармпрепаратов, содержащих радиоактивные изотопы и способных специфически связываться с определенными белками, является одним из подходов, применяемых при лечении или диагностике злокачественных опухолей. При этом важной задачей является решение проблемы накопления радиоактивности в почках после введения в организм радиоконъюгатов с молекулярной массой менее 70 КДа. Цель исследования – выявление наиболее эффективных подходов, способствующих уменьшению накопления радиоактивности в почках при использовании радиоконъюгатов в ходе диагностики и таргетной терапии опухолевых заболеваний. Материал и методы. Проведен поиск литературы по теме обзора в электронных базах данных PubMed, Scopus и Web of Science в период с 1987 по 2023 г., 82 статьи использовано при написании обзора. Результаты. Представлено описание подходов, используемых для улучшения биораспределения радиоконъюгатов, главным образом, в доклинических исследованиях, описаны достоинства и недостатки таких методик. Заключение. Уменьшение радиоактивности в почках при использовании радиоконъюгатов молекул с молекулярной массой менее 70 КДа является непростой, но решаемой задачей. Сделан вывод о высокой перспективности использования в подобных радиоконъюгатах расщепляемых линкеров, поскольку такой подход не меняет фармакокинетику таких препаратов. Отмечено, что преимуществом введения сопутствующих веществ по сравнению с изменением строения радиоконъюгатов является меньшая зависимость от особенностей того или иного радиофармпрепарата (РФП). Также этот подход не требует предварительной работы по модификации радиоконъюгата, однако имеет ограниченную эффективность.

Administration of pharmaceuticals containing radioactive isotopes and capable of specific binding to certain proteins is one of the approaches used in the treatment or diagnosis of malignant tumors. High renal accumulation of radioactive compounds after administration of radioconjugates with molecular mass less than 70 KDa is of the challenges that need to be solved. The purpose of the study was to identify the most effective approaches to reduce the accumulation of radioactivity in the kidneys after administration of radioconjugates used for diagnostic imaging and targeted therapy for cancer. Material and Methods. We conducted a literature search on the topic of the review in the electronic databases PubMed, Scopus and Web of Science from 1987 to 2023, 82 articles were used for writing the review. Results. The review presents a description of approaches used to improve the biodistribution of radioconjugates, mainly in preclinical studies. The advantages and disadvantages of such techniques have been described. Conclusion. Reducing renal radioactivity using radioconjugates of molecules with molecular masses less than 70 KDa is a challenging but achievable task. It is concluded that the use of cleavable linkers in such radioconjugates is highly promising, since this approach does not change the pharmacokinetics of such drugs. It is noted that the advantage of introducing concomitant substances compared to changing the structure of radioconjugates is a lesser dependence on the characteristics of a particular radiopharmaceutical. This approach also does not require prior work to modify the radioconjugate, but has limited efficiency.

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