Email this article 
Post a Comment Anti-tumor activity of radiopharmaceutical medication based on biospecific antibodies to tumor-associated stroma elements and 177lutecium
- Authors: Trashkov A.P.1,2, Gagloeva T.D.1,2, Budko A.I.1, Petrovskiy A.N.1, Timaeva O.I.2, Tsygan N.V.1,3, Stanzhevsky A.A.1,4, Vasiliev A.G.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
-
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 6 (2022)
- Pages: 35-44
- Section: Original studies
- URL: https://journals.rcsi.science/pediatr/article/view/133039
- DOI: https://doi.org/10.17816/PED13635-44
- ID: 133039
Cite item
Open Access
Access granted
Subscription Access
Abstract
Radiopharmaceutical targeted medication based on biospecific antibodies to tumor-associated stroma elements and 177lutecium (177Lu-DOTA-anti-CTLA4-GITR) potential anti-tumor activity was studied in two courses: one-time administration and two injections with a considerable lag. Subcutaneously transplanted experimental colonic carcinoma (AKATOL; cell line — CT26 EGFP) with high expression of green fluorescent protein (eGFP) and additional expression of target tumor-associated stroma molecules — CTLA4 and GITR was used as a model in BALB/c male mice. The experimental radiopharmaceutical targeted medication proved to possess high pharmacologic activity against the tumor under study. It was apparent in valid increase of experimental animals’ mean lifespan, tumor debut latent period inhibition and clinically valid tumor growth rate slowdown. Double administration of 177Lu-DOTA-anti-CTLA4-GITR proved to be more effective than one-time one, however neither of them managed to yield statistically valid difference in safety levels.
Full Text
##article.viewOnOriginalSite##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, Gatchina, Leningrad Region; 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; Junior Research Associate, Neorocognitive Research Resource Center
Russian Federation, Gatchina, Leningrad Region; MoscowAlexander I. Budko
B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”
Email: budko_ai@pnpi.nrcki.ru
Laboratory Researcher, Center of Preclinical and Clinical Research
Russian Federation, Gatchina, Leningrad RegionAndrey N. Petrovskiy
B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”
Email: petrovskiy_an@pnpi.nrcki.ru
MD, PhD, Senior Research Associate, Center of Preclinical and Clinical Research
Russian Federation, Gatchina, Leningrad RegionOlyesya 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, 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.), Assistant Professor, Leading Research Associate, Center of Preclinical and Clinical Research; Vice-Head, Department of the Nervous Diseases
Russian Federation, Gatchina, Leningrad Region; 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.), Professor, Leading Research Associate, Center of Preclinical and Clinical Research; Vice-Director Research
Russian Federation, Gatchina, Leningrad Region; 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 Course of Immunopathology
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; Head of the Department Biomedical Technologies
Russian Federation, Gatchina, Leningrad Region; MoscowReferences
- Belozertseva IV, Blinov DV, Krasilshchikova MS, ed. Rukovodstvo po soderzhaniyu i ispolzovaniyu laboratornykh zhivotnykh. 8th ed. Moscow: IRBIS; 2017. 336 p. (In Russ.)
- Vasil’ev AG, Komyakov BK, Tagirov NS, Musaev SA. Percutaneous nephrolithitripsy in the treatment of coral calculus nephrolithiasis. Bulletin of The Saint Petersburg State Medical Academy named after I.I. Mechnikov. 2009;4(33):183–186. (In Russ.)
- Tagirov NS, Nazarov TH, Vasil’ev AG, et al. The experience of using percutaneous nephrolithotripsy and contact ureterolithotripsy in the complex treatment of urolithiasis. Preventive and Clinical Medicine. 2012;4(45):30–33. (In Russ.)
- Trashkov AP, Brus TV, Vasil’ev AG, et al. Biochemical profile of rats with non-alcoholic fatty liver disease of various gravity and its correction with Remaxol. Pediatrician (St. Petersburg). 2017;8(4):78–85. (In Russ.)
- Trashkov AP, Vasil’ev AG, Kovalenko AL, Tagirov NS. Metabolic therapy of nephrolithiasis in two different rat models of kidney disease. Eksperimentalnaya i Klinicheskaya Farmakologiya. 2015;78(3):17–21. (In Russ.) doi: 10.30906/0869-2092-2015-78-3-17-21
- Trashkov AP, Vasil’ev AG, Cygan 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. (In Russ.) doi: 10.17816/PED11645-53
- Trashkov AP, Gagloeva TD, Budko AI, et al. Biodistribution and kinetic characters of radiopharmaceutical medication based on biospecific antibodies to tumor-associated stroma elements and 177 lutcium. Pediatrician (St. Petersburg). 2022;13(5)51–60. doi: 10.17816/PED13551-60
- Trashkov AP, Panchenko AV, Kayukova ES, et al. Leikemiya P-388 u myshei linii CDF1 kak test-sistema opukhol-assotsiirovannogo neoangiogeneza i giperkoagulyatsii. Byulleten’ Eksperimental’noj Biologii i Mediciny. 2014;158(10):500–502.
- Khaytsev NV, Vasiliev AG, Trashkov AP, et al. The influence of sex and age upon response of white rats to hypoxic hypoxia. Pediatrician (St. Petersburg). 2015;6(2):71–77. doi: 10.17816/PED6271-77
- Sheremeta MS, Trukhin AA, Korchagina MO. The use of radioactive substances in medicine — history and development prospects. Problems of Endocrinology. 2021;67(6):59–67. (In Russ.) doi: 10.14341/probl12824
- 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
- Klingler M, Hörmann AA, Guggenberg EV. Cholecystokinin-2 receptor targeting with radiolabeled peptides: current status and future directions. Curr Med Chem. 2020;27(41):7112–7132. doi: 10.2174/0929867327666200625143035
- Ma X, Ding Y, Li W, et al. Diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms by nuclear medicine: Update and future perspective. Front Oncol. 2022;12:1061065. doi: 10.3389/fonc.2022.1061065
- Morgenstern A, Apostolidis C, Kratochwil C, et al. An overview of targeted alpha therapy with 225Actinium and 213Bismuth. Curr Radiopharm. 2018;11(3):200–208. doi: 10.2174/1874471011666180502104524
- Pigarev SE, Panchenko AV, Yurova MN, et al. Evaluation of the genotoxic and antigenotoxic potential of lignin-derivative BP-C2 in the comet assay in vivo. Environmental Research. 2021;192:110321. doi: 10.1016/j.envres.2020.110321
- Panchenko AV, Popovich IG, Egormin PA, 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
- Sgouros G. Radiopharmaceutical Therapy. Health Phys. 2019;116(2):175–178. doi: 10.1097/HP.0000000000001000
- St James S, Bednarz B, Benedict S, et al. Current Status of Radiopharmaceutical Therapy. Int J Radiat Oncol Biol Phys. 2021;109(4):891–901. doi: 10.1016/j.ijrobp.2020.08.035
- 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
- Tsygan NV, Trashkov AP, Litvinenko IV, et al. Autoimmunity in acute ischemic stroke and the role of blood-brain barrier: the dark side or the light one? Frontiers of Medicine. 2019;13(4):420–426.
Supplementary files
