Исследование биораспределения и кинетических характеристик радиофармацевтического лекарственного препарата на основе биспецифических антител к элементам опухоль-ассоциированной стромы и изотопа лютеция 177

Александр Петрович Трашков; Тамара Давидовна Гаглоева; Александр Игоревич Будько; Олеся Иршатовна Тимаева; Марина Юрьевна Копаева; Антон Борисович Черепов; Николай Васильевич Цыган; Андрей Алексеевич Станжевский; Андрей Глебович Васильев; Мария Александровна Пахомова; Дмитрий Николаевич Майстренко; Кристина Анатольевна Сергунова; Дмитрий Сергеевич Сысоев; Сергей Васильевич Шатик; Дмитрий Олегович Антуганов; Андрей Леонидович Коневега

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

Alexander P. Trashkov B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”; National Research Center “Kurchatov Institute”
Tamara D. Gagloeva B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”; National Research Center “Kurchatov Institute”
Alexander I. Budko B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”
Olyesya I. Timaeva National Research Center “Kurchatov Institute”
Marina Yu. Kopaeva National Research Center “Kurchatov Institute”
Anton B. Cherepov National Research Center “Kurchatov Institute”
Nikolay V. Tsygan B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”; Kirov Military Medical Academy
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
Andrey G. Vasiliev St. Petersburg State Pediatric Medical University
Mariya A. Pahomova St. Petersburg State Pediatric Medical University
Dmitri N. Maistrenko A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies
Christina A. Sergunova National Research Center “Kurchatov Institute”
Dmitri S. Sysoev A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies
Sergei V. Shatic A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies
Dmitri O. Antuganov A.M. Granov Russian Scientific Center for Radiology and Surgical Technologies
Andrei L. Konevega B.P. Konstantinov Petersburg Nuclear Physics Institute of National Research Centre “Kurchatov Institute”; National Research Center “Kurchatov Institute”

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.