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

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Abstract

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.

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About the authors

Alexander P. Trashkov

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

Author for correspondence.
Email: alexander.trashkov@gmail.com

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

Russian Federation, Leningrad Region, Gatchina; Moscow

Tamara D. 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”

Russian Federation, Leningrad Region, Gatchina; Moscow

Alexander I. 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

Russian Federation, Leningrad Region, Gatchina

Olyesya I. 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

Russian Federation, Moscow

Marina Yu. Kopaeva

National Research Center “Kurchatov Institute”

Email: kopaeva_mu@nrcki.ru

Researcher, Resourse Center of Neurocognitive Technologies

Russian Federation, Moscow

Anton B. Cherepov

National Research Center “Kurchatov Institute”

Email: cherepov_ab@nrcki.ru

Leding Engeneer, Resourse Center of Neurocognitive Technologies

Russian Federation, Moscow

Nikolay V. 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

Russian Federation, Leningrad Region, Gatchina; Saint Petersburg

Andrei A. 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

Russian Federation, Leningrad Region, Gatchina; Saint Petersburg

Andrey G. 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

Russian Federation, Saint Petersburg

Mariya A. Pahomova

St. Petersburg State Pediatric Medical University

Email: mariya.pahomova@mail.ru

Senior Research Associate, Research Center

Russian Federation, Saint Petersburg

Dmitri N. Maistrenko

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

Email: info@rrcrst.ru

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

Russian Federation, Saint Petersburg

Christina A. Sergunova

National Research Center “Kurchatov Institute”

Email: sergunova_ka@nrcki.ru

PhD, Head Academic Secretary

Russian Federation, Moscow

Dmitri S. 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

Russian Federation, Saint Petersburg

Sergei V. Shatic

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

Email: s_shatik@hotmail.com

PhD, Head Department Cyclotron Radiochemical Medications

Russian Federation, Saint Petersburg

Dmitri O. Antuganov

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

Email: info@rrcrst.ru

Research Associate, Laboratory of Radiopharmaceutical Technologies

Russian Federation, Saint Petersburg

Andrei L. 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”

Russian Federation, Leningrad Region, Gatchina; Moscow

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Supplementary files

Supplementary Files
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1. JATS XML
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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