Evgenii Zavjalov1,2, Alexander Zaboronok1,3, Vladimir Kanygin1, Anna Kasatova1,4, Aleksandr Kichigin1, Rinat Mukhamadiyarov1,5, Ivan Razumov1,2, Tatiana Sycheva4, Bryan J Mathis3, Sakura Eri B Maezono6, Akira Matsumura3, Sergey Taskaev4,7. 1. Laboratory of medical and biological problems of BNCT, Novosibirsk State University, Novosibirsk, Russia. 2. Center for Genetic Resources of Laboratory Animals, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia. 3. Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. 4. Budker Institute of Nuclear Physics, Novosibirsk, Russia. 5. Research Institute for Complex Issues of Cardiovascular Diseases SB RAS, Kemerovo, Russia. 6. PhD Program in Human Biology, School of Integrative and Global Majors and International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan. 7. Laboratory of BNCT, Novosibirsk State University, Novosibirsk, Russia.
Abstract
Purpose: To evaluate the efficacy of boron neutron capture therapy (BNCT) for a heterotopic U87 glioblastoma model in SCID mice using boron phenylalanine (BPA), sodium borocaptate (BSH) and liposomal BSH as boron compounds at a unique, accelerator-based neutron source.Materials and methods: Glioblastoma models were obtained by subcutaneous implantation of U87 cells in the right thighs of SCID mice before administration of 350 mg/kg of BPA (BPA-group), 100 mg/kg of BSH (BSH-group) or 100 mg/kg of BSH in PEGylated liposomes (liposomal BSH-group) into the retroorbital sinus. Liposomes were prepared by reverse-phase evaporation. Neutron irradiation was carried out at a proton accelerator with a lithium target developed for BNCT at the Budker Institute of Nuclear Physics, Novosibirsk, Russian Federation. A proton beam current integral of 3 mA/h and energy of 2.05 MeV were used for neutron generation. Results: Boron compound accumulation in tumor tissues at the beginning of irradiation was higher in the BPA group, followed by the Liposomal BSH and BSH groups. Tumor growth was significantly slower in all irradiated mice from the 7th day after BNCT compared to untreated controls (p < .05). Tumor growth in all treated groups showed no large variation, apart from the Irradiation only group and the BPA group on the 7th day after BNCT. The overall trend of tumor growth was clear and the differences between treatment groups became significant from the 50th day after BNCT. Tumor growth was significantly slower in the Liposomal BSH group compared to the Irradiation only group on the 50th (p = .012), 53rd (p = .005), and the 57th (p = .021) days after treatment. Tumor growth in the Liposomal BSH group was significantly different from that in the BPA group on the 53rd day after BNCT (p = .021) and in the BSH group on the 50th (p = .024), 53rd (p = .015), and 57th (p = .038) days after BNCT. Skin reactions in the form of erosions and ulcers in the tumor area developed in treated as well as untreated animals with further formation of fistulas and necrotic decay cavities in most irradiated mice.Conclusions: We observed a tendency of BNCT at the accelerator-based neutron source to reduce or suspend the growth of human glioblastoma in immunodeficient animals. Liposomal BSH showed better long-term results compared to BPA and non-liposomal BSH. Further modifications in liposomal boron delivery are being studied to improve treatment outcomes.
Purpose: To evaluate the efficacy of boron neutron capture therapy (BNCT) for a heterotopic U87 glioblastoma model in SCIDmice using boron phenylalanine (BPA), sodium borocaptate (BSH) and liposomal BSH as boron compounds at a unique, accelerator-based neutron source.Materials and methods: Glioblastoma models were obtained by subcutaneous implantation of U87 cells in the right thighs of SCIDmice before administration of 350 mg/kg of BPA (BPA-group), 100 mg/kg of BSH (BSH-group) or 100 mg/kg of BSH in PEGylated liposomes (liposomal BSH-group) into the retroorbital sinus. Liposomes were prepared by reverse-phase evaporation. Neutron irradiation was carried out at a proton accelerator with a lithium target developed for BNCT at the Budker Institute of Nuclear Physics, Novosibirsk, Russian Federation. A proton beam current integral of 3 mA/h and energy of 2.05 MeV were used for neutron generation. Results:Boron compound accumulation in tumor tissues at the beginning of irradiation was higher in the BPA group, followed by the Liposomal BSH and BSH groups. Tumor growth was significantly slower in all irradiated mice from the 7th day after BNCT compared to untreated controls (p < .05). Tumor growth in all treated groups showed no large variation, apart from the Irradiation only group and the BPA group on the 7th day after BNCT. The overall trend of tumor growth was clear and the differences between treatment groups became significant from the 50th day after BNCT. Tumor growth was significantly slower in the Liposomal BSH group compared to the Irradiation only group on the 50th (p = .012), 53rd (p = .005), and the 57th (p = .021) days after treatment. Tumor growth in the Liposomal BSH group was significantly different from that in the BPA group on the 53rd day after BNCT (p = .021) and in the BSH group on the 50th (p = .024), 53rd (p = .015), and 57th (p = .038) days after BNCT. Skin reactions in the form of erosions and ulcers in the tumor area developed in treated as well as untreated animals with further formation of fistulas and necrotic decay cavities in most irradiated mice.Conclusions: We observed a tendency of BNCT at the accelerator-based neutron source to reduce or suspend the growth of humanglioblastoma in immunodeficient animals. Liposomal BSH showed better long-term results compared to BPA and non-liposomal BSH. Further modifications in liposomal boron delivery are being studied to improve treatment outcomes.
Authors: V V Kanygin; A I Kasatova; E L Zavjalov; I A Razumov; S I Kolesnikov; A I Kichigin; O I Solov'eva; A R Tsygankova; S Yu Taskaev; D A Kasatov; T V Sycheva; V A Byvaltsev Journal: Bull Exp Biol Med Date: 2022-01-10 Impact factor: 0.804
Authors: David M Campkin; Yuna Shimadate; Barbara Bartholomew; Paul V Bernhardt; Robert J Nash; Jennette A Sakoff; Atsushi Kato; Michela I Simone Journal: Molecules Date: 2022-05-26 Impact factor: 4.927
Authors: Vladimir Kanygin; Alexander Zaboronok; Iuliia Taskaeva; Evgenii Zavjalov; Rinat Mukhamadiyarov; Aleksandr Kichigin; Anna Kasatova; Ivan Razumov; Roman Sibirtsev; Bryan J Mathis Journal: J Fluoresc Date: 2020-10-19 Impact factor: 2.217
Authors: Vladimir Kanygin; Aleksandr Kichigin; Alexander Zaboronok; Anna Kasatova; Elena Petrova; Alphiya Tsygankova; Evgenii Zavjalov; Bryan J Mathis; Sergey Taskaev Journal: Biology (Basel) Date: 2022-01-14