Biodistribution and kinetic characters of radiopharmaceutical medication based on biospecific antibodies to tumor-associated stroma elements and 177lutcium

Alexander P. Trashkov; Трашков Александр Петрович; Tamara D. Gagloeva; Гаглоева Тамара Давидовна; Alexander I. Budko; Будько Александр Игоревич; Olyesya I. Timaeva; Тимаева Олеся Иршатовна; Marina Yu. Kopaeva; Копаева Марина Юрьевна; Anton B. Cherepov; Черепов Антон Борисович; Nikolay V. Tsygan; Цыган Николай Васильевич; Andrei A. Stanzhevsky; Станжевский Андрей Алексеевич; Andrey G. Vasiliev; Васильев Андрей Глебович; Mariya A. Pahomova; Пахомова Мария Александровна; Dmitri N. Maistrenko; Майстренко Дмитрий Николаевич; Christina A. Sergunova; Сергунова Кристина Анатольевна; Dmitri S. Sysoev; Сысоев Дмитрий Сергеевич; Sergei V. Shatic; Шатик Сергей Васильевич; Dmitri O. Antuganov; Антуганов Дмитрий Олегович; Andrei L. Konevega; Коневега Андрей Леонидович

doi:10.17816/PED13551-60

Biodistribution and kinetic characters of radiopharmaceutical medication based on biospecific antibodies to tumor-associated stroma elements and 177lutcium

作者: Trashkov A.P.¹^,2, Gagloeva T.D.¹^,2, Budko A.I.¹, Timaeva O.I.², Kopaeva M.Y.², Cherepov A.B.², Tsygan N.V.¹^,3, Stanzhevsky A.A.¹^,4, Vasiliev A.G.⁵, Pahomova M.A.⁵, Maistrenko D.N.⁴, Sergunova C.A.², Sysoev D.S.⁴, Shatic S.V.⁴, Antuganov D.O.⁴, Konevega A.L.¹^,2
隶属关系:
1. B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”
2. National Research Center “Kurchatov Institute”
3. Kirov Military Medical Academy
4. A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies
5. St. Petersburg State Pediatric Medical University
期: 卷 13, 编号 5 (2022)
页面: 51-60
栏目: Original studies
URL: https://journals.eco-vector.com/pediatr/article/view/119958
DOI: https://doi.org/10.17816/PED13551-60
ID: 119958

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Biodistribution and kinetics were studied of potentially target biospecific radiopharmaceutical medication for the treatment of malignant tumors of various histologic type and location with expression of cytotoxic T-lymphocyte membrane associated glycoprotein 4 and glucocorticoid Induced Tumor Necrosis Factor Receptor) — ¹⁷⁷Lu-DOTA-anti-CTLA4-GITR. Colorectal cancer experimental model has been successfully reproduced by means of murine large intestine experimental adenocarcinoma cells (AKATOL) СТ26 EGFR) direct transplantation. The model was characteristic of moderate growth rate and practically complete absence of metastatic spread. Immunohistochemical assay of tumor tissue has revealed satisfactory expression level of target antigens for the medication under study, i.e. cytotoxic T-lymphocyte associated protein 4 (CTLA4) as well as membrane receptor of tumor necrosis factor group (GITR). This medication ¹⁷⁷Lu-DOTA-anti-CTLA4-GITR has been shown to store in the tumor tissue. Its major pathways out of the organism were through urinary system. On the other hand, the medication has also been demonstrated to store in non-target tissues, namely: kidneys, liver, large intestine. The results of this study may be used in preclinical studies of medications and serve as a basis for broader studies of ¹⁷⁷Lu-DOTA-anti-CTLA4-GITR and its safety.

关键词

177Lu-DOTA-anti-CTLA4-GITR, experimental studies, medication’s kinetic character, biodistribution, tumor, mice, intravenous injection

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作者简介

Alexander Trashkov

B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”; National Research Center “Kurchatov Institute”

编辑信件的主要联系方式.
Email: alexander.trashkov@gmail.com

MD, PhD, Head, Center of Preclinical and Clinical Research

俄罗斯联邦, Leningrad Region, Gatchina; Moscow

Tamara Gagloeva

B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”; National Research Center “Kurchatov Institute”

Email: gagloeva_td@pnpi.nrcki.ru

Junior Research Associate, Center of Preclinical and Clinical Research, B.P. Konstantinov Petersburg Nuclear Physics Institute of NRC “Kurchatov Institute”; Junior Research Associate, Neorocognitive Research Resource Center, National Research Centre “Kurchatov Institute”

俄罗斯联邦, Leningrad Region, Gatchina; Moscow

Alexander Budko

B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”

Email: budko_ai@pnpi.nrcki.ru

MD, PhD, Laboratory Researcher, Center of Preclinical and Clinical Research

俄罗斯联邦, Leningrad Region, Gatchina

Olyesya Timaeva

National Research Center “Kurchatov Institute”

Email: timaeva_oi@nrcki.ru

PhD, Academic Secretary, Kurchatov Complex of Nano-, Bio-, Informational, Cognitive and Socio-Humanitarian nature-like technologies

俄罗斯联邦, Moscow

Marina Kopaeva

National Research Center “Kurchatov Institute”

Email: kopaeva_mu@nrcki.ru

Researcher, Resourse Center of Neurocognitive Technologies

俄罗斯联邦, Moscow

Anton Cherepov

National Research Center “Kurchatov Institute”

Email: cherepov_ab@nrcki.ru

Leding Engeneer, Resourse Center of Neurocognitive Technologies

俄罗斯联邦, Moscow

Nikolay Tsygan

B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”; Kirov Military Medical Academy

Email: tsygan_nv@pnpi.nrcki.ru

MD, PhD, Dr. Sci. (Med.), Associate Professor, Leading Research Associate, Center of Preclinical and Clinical Research, B.P. Konstantinov Petersburg Nuclear Physics Institute of NRC “Kurchatov Institute”; Vice-Head, Department of the Nervous Diseases, Kirov Military Medical Academy

俄罗斯联邦, Leningrad Region, Gatchina; Saint Petersburg

Andrei Stanzhevsky

B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”; A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies

Email: stanzhevsky_aa@pnpi.nrcki.ru

MD, PhD, Dr. Sci. (Med.), Associate Professor, Leading Research Associate, Center of Preclinical and Clinical Research, B.P. Konstantinov Petersburg Nuclear Physics Institute of NRC “Kurchatov Institute”; Vice-Director Research, A.M. Granov Russian Research Center for Radiology and Surgical Technologies, Ministry of Health of the Russian Federation

俄罗斯联邦, Leningrad Region, Gatchina; Saint Petersburg

Andrey Vasiliev

St. Petersburg State Pediatric Medical University

Email: avas7@mail.ru

MD, PhD, Dr. Sci. (Med.), Professor, Head, Department of Pathologic Physiology with Courses Immunopathology and Medical Informatics

俄罗斯联邦, Saint Petersburg

Mariya Pahomova

St. Petersburg State Pediatric Medical University

Email: mariya.pahomova@mail.ru

Senior Research Associate, Research Center

俄罗斯联邦, Saint Petersburg

Dmitri Maistrenko

A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies

Email: info@rrcrst.ru

MD, PhD, Dr. Sci. (Med.), Professor, Director

俄罗斯联邦, Saint Petersburg

Christina Sergunova

National Research Center “Kurchatov Institute”

Email: sergunova_ka@nrcki.ru

PhD, Head Academic Secretary

俄罗斯联邦, Moscow

Dmitri Sysoev

A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies

Email: info@rrcrst.ru

PhD, Head, Group for research and production of equipment for nuclear medicine

俄罗斯联邦, Saint Petersburg

Sergei Shatic

A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies

Email: s_shatik@hotmail.com

PhD, Head Department Cyclotron Radiochemical Medications

俄罗斯联邦, Saint Petersburg

Dmitri Antuganov

A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies

Email: info@rrcrst.ru

Research Associate, Laboratory of Radiopharmaceutical Technologies

俄罗斯联邦, Saint Petersburg

Andrei Konevega

B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”; National Research Center “Kurchatov Institute”

Email: konevega_al@pnpi.nrcki.ru

PhD, Head of the Department Molecular and Radiological Biophysics, B.P. Konstantinov Petersburg Nuclear Physics Institute of NRC “Kurchatov Institute”; Head of the Department Biomedical Technologies, National Research Centre “Kurchatov Institute”

俄罗斯联邦, Leningrad Region, Gatchina; Moscow

参考

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2. Fig. 1. Distribution of 177Lu-DOTA-anti-CTLA4-GITR radiopharmaceutical medication in the tumor target animal organism. The portion of the total dose introduced into the animal registered in a separate organ (Organ_dose)

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