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
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隶属关系:
- 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
- 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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详细
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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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; MoscowTamara 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; MoscowAlexander 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, GatchinaOlyesya 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, MoscowMarina Kopaeva
National Research Center “Kurchatov Institute”
Email: kopaeva_mu@nrcki.ru
Researcher, Resourse Center of Neurocognitive Technologies
俄罗斯联邦, MoscowAnton Cherepov
National Research Center “Kurchatov Institute”
Email: cherepov_ab@nrcki.ru
Leding Engeneer, Resourse Center of Neurocognitive Technologies
俄罗斯联邦, MoscowNikolay 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 PetersburgAndrei 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 PetersburgAndrey 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 PetersburgMariya Pahomova
St. Petersburg State Pediatric Medical University
Email: mariya.pahomova@mail.ru
Senior Research Associate, Research Center
俄罗斯联邦, Saint PetersburgDmitri 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 PetersburgChristina Sergunova
National Research Center “Kurchatov Institute”
Email: sergunova_ka@nrcki.ru
PhD, Head Academic Secretary
俄罗斯联邦, MoscowDmitri 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 PetersburgSergei 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 PetersburgDmitri 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 PetersburgAndrei 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
- Ataei A, Solovyeva VV, Rizvanov AA, Arab SSh. Tumor microenvironment: A key contributor to cancer progression, invasion, and drug resistance. Uchenye Zapiski Kazanskogo Universiteta. Seriya Estestvennye Nauki. 2020;162(4):507–528. (In Russ.) doi: 10.26907/2542-064X.2020.4.507-528
- Zibirov RF, Mozerov SA. Characterization of the tumor cell microenvironment. P.A. Herzen Journal of Oncology. 2018;7(2):67–72. (In Russ.) doi: 10.17116/onkolog20187267-72
- Lyzhko NA. Molecular-genetic mechanisms of initiation, promotion and progression of tumors. Russian Journal of Biotherapy. 2017;16(4):7–17. (In Russ.) doi: 10.17650/1726-9784-2017-16-4-7-17
- Belozertseva IV, Blinov DV, Krasil’shchikova MS, editors. Rukovodstvo po soderzhaniyu i ispol’zovaniyu laboratornykh zhivotnykh. 8-e edition. Moscow: IRBIS, 2017. 336 p. (In Russ.)
- Kaprin AD, Starinskii VV, Shakhzadova AO, editors. Sostoyanie onkologicheskoi pomoshchi naseleniyu Rossii v 2021 godu. Moscow: MNIOI im. P.A. Gertsena — filial FGBU “NMITS radiologiI” Minzdrava Rossii, 2022. 239 p. (In Russ.)
- Trashkov AP, Vasiliev AG, Tsygan NV, et al. Antithrombotic therapy in oncology: contemporary concepts and pending problems. Pediatrician (St. Petersburg). 2012;3(2):3–19. (In Russ.)
- Trashkov AP, Muzhikyan AA, Tsygan NV, et al. Сomparative analysis of acridineacetate-containing compounds’ radio-sensitizing effect during malignant tumor experimental radiotherapy in a metastatic colorectal cancer model in BALB/C mice. Pediatrician (St. Petersburg). 2020;11(6):45–53. doi: 10.17816/PED11645-53
- Trashkov AP, Panchenko AV, Kayukova ES, et al. Leikemiya R-388 u myshei linii CDF1 kak test-sistema opukhol’-assotsiirovannogo neoangiogeneza i giperkoagulyatsii. Byulleten’ eksperimental’noj biologii i mediciny. 2014;158(10):500–502. (In Russ.)
- Cook J, Hagemann T. Tumour-associated macrophages and cancer. Curr Opin Pharmacol. 2013;13(4): 595–601. doi: 10.1016/j.coph.2013.05.017
- Denkert C, Loibl S, Noske A, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010;28(1):105–113. doi: 10.1200/JCO.2009.23.7370
- Gong JE, Jin YJ, Kim JE, et al. Comparison of cisplatin-induced anti-tumor response in CT26 syngeneic tumors of three BALB/c substrains. Lab Anim Res. 2021;37(1):33. doi: 10.1186/s42826-021-00110-3
- Gordon SR, Maute RL, Dulken BW, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545(7655): 495–499. doi: 10.1038/nature22396
- Loeuillard E, Yang J, Buckarma E, et al. Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma. J Clin Invest. 2020;130(10):5380–5396. doi: 10.1172/JCI137110
- Liu C-C, Yang H, Zhang R, et al. Tumour-associated antigens and their anti-cancer applications. Eur J Cancer Care (Engl). 2017;26(5): e12446. doi: 10.1111/ecc.12446
- Pan Y, Yu Y, Wang X, Zhang T. Tumor-associated macrophages in tumor immunity. Front Immunol. 2020;11:583084. doi: 10.3389/fimmu.2020.583084
- Panchenko AV, Popovich IG, Trashkov AP, et al. Biomarkers of aging, life span and spontaneous carcinogenesis in the wild type and HER-2 transgenic FVB/N female mice. Biogerontology. 2016;17(2):317–324. doi: 10.1007/s10522-015-9611-y
- Taniura T, Iida Y, Kotani H, et al. Immunogenic chemotherapy in two mouse colon cancer models. Cancer Sci. 2020;111(10):3527–3539. doi: 10.1111/cas.14624
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