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Biodistribution and kinetic characters of radiopharmaceutical medication based on biospecific antibodies to tumor-associated stroma elements and 177lutcium
- Authors: 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
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Affiliations:
- B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”
- National Research Center “Kurchatov Institute”
- Kirov Military Medical Academy
- A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies
- St. Petersburg State Pediatric Medical University
- Issue: Vol 13, No 5 (2022)
- Pages: 51-60
- Section: Original studies
- URL: https://journals.eco-vector.com/pediatr/article/view/119958
- DOI: https://doi.org/10.17816/PED13551-60
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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; MoscowTamara 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; MoscowAlexander 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, GatchinaOlyesya 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, MoscowMarina Yu. Kopaeva
National Research Center “Kurchatov Institute”
Email: kopaeva_mu@nrcki.ru
Researcher, Resourse Center of Neurocognitive Technologies
Russian Federation, MoscowAnton B. Cherepov
National Research Center “Kurchatov Institute”
Email: cherepov_ab@nrcki.ru
Leding Engeneer, Resourse Center of Neurocognitive Technologies
Russian Federation, MoscowNikolay 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 PetersburgAndrei 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 PetersburgAndrey 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 PetersburgMariya A. Pahomova
St. Petersburg State Pediatric Medical University
Email: mariya.pahomova@mail.ru
Senior Research Associate, Research Center
Russian Federation, Saint PetersburgDmitri 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 PetersburgChristina A. Sergunova
National Research Center “Kurchatov Institute”
Email: sergunova_ka@nrcki.ru
PhD, Head Academic Secretary
Russian Federation, MoscowDmitri 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 PetersburgSergei 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 PetersburgDmitri 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 PetersburgAndrei 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; MoscowReferences
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