TY - JOUR

T1 - Biodistribution of10 b in glioma orthotopic xenograft mouse model after injection of l-para-boronophenylalanine and sodium borocaptate

AU - Gubanova, Natalya V.

AU - Tsygankova, Alphiya R.

AU - Zavjalov, Evgenii L.

AU - Romashchenko, Alexander V.

AU - Orlov, Yuriy L.

N1 - Funding Information: This research was funded by the Ministry of Science and High Education via the Institute of Cytology and Genetics grant number 0259-2021-0014, and Russian Science Foundation grant number 14-32-00006. The authors acknowledge the Centre for Genetic Resources of Laboratory Animals at the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, supported by the Ministry of Education and Science of Russia (Unique identifier of the project RFMEFI62119X0023). The authors also acknowledge the Centre of Collective Usage of the Nikolaev Institute of Inorganic Chemistry of Siberian Branch Russian Academy of Sciences, where the boron concentrations were determined. Funding Information: Funding: This research was funded by the Ministry of Science and High Education via the Institute of Cytology and Genetics grant number 0259-2021-0014, and Russian Science Foundation grant number 14-32-00006. Funding Information: Acknowledgments: The authors acknowledge the Centre for Genetic Resources of Laboratory Animals at the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, supported by the Ministry of Education and Science of Russia (Unique identifier of the project RFMEFI62119X0023). The authors also acknowledge the Centre of Collective Usage of the Nikolaev Institute of Inorganic Chemistry of Siberian Branch Russian Academy of Sciences, where the boron concentrations were determined. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7

Y1 - 2021/7

N2 - Boron neutron capture therapy (BNCT) is based on the ability of the boron-10 (10 B) isotope to capture epithermal neutrons, as a result of which the isotope becomes unstable and decays into kinetically active elements that destroy cells where the nuclear reaction has occurred. The boron-carrying compounds—L-para-boronophenylalanine (BPA) and sodium mercaptoundecahydro-closo-dodecaborate (BSH)—have low toxicity and, today, are the only representatives of such compounds approved for clinical trials. For the effectiveness and safety of BNCT, a low boron content in normal tissues and substantially higher content in tumor tissue are required. This study evaluated the boron concentration in intracranial grafts of human glioma U87MG cells and normal tissues of the brain and other organs of mice at 1, 2.5 and 5 h after administration of the boron-carrying compounds. A detailed statistical analysis of the boron biodistribution dynamics was performed to find a ‘window of opportunity’ for BNCT. The data demonstrate variations in boron accumulation in different tissues depending on the compound used, as well as significant inter-animal variation. The protocol of administration of BPA and BSH compounds used did not allow achieving the parameters necessary for the successful course of BNCT in a glioma orthotopic xenograft mouse model.

AB - Boron neutron capture therapy (BNCT) is based on the ability of the boron-10 (10 B) isotope to capture epithermal neutrons, as a result of which the isotope becomes unstable and decays into kinetically active elements that destroy cells where the nuclear reaction has occurred. The boron-carrying compounds—L-para-boronophenylalanine (BPA) and sodium mercaptoundecahydro-closo-dodecaborate (BSH)—have low toxicity and, today, are the only representatives of such compounds approved for clinical trials. For the effectiveness and safety of BNCT, a low boron content in normal tissues and substantially higher content in tumor tissue are required. This study evaluated the boron concentration in intracranial grafts of human glioma U87MG cells and normal tissues of the brain and other organs of mice at 1, 2.5 and 5 h after administration of the boron-carrying compounds. A detailed statistical analysis of the boron biodistribution dynamics was performed to find a ‘window of opportunity’ for BNCT. The data demonstrate variations in boron accumulation in different tissues depending on the compound used, as well as significant inter-animal variation. The protocol of administration of BPA and BSH compounds used did not allow achieving the parameters necessary for the successful course of BNCT in a glioma orthotopic xenograft mouse model.

KW - BNCT

KW - Boron neutron capture therapy

KW - BPA

KW - BSH

KW - Glioma

KW - L-para-boronophenylalanine

KW - Mouse model

KW - Sodium borocaptate

UR - http://www.scopus.com/inward/record.url?scp=85109157043&partnerID=8YFLogxK

U2 - 10.3390/biomedicines9070722

DO - 10.3390/biomedicines9070722

M3 - Article

C2 - 34201895

AN - SCOPUS:85109157043

VL - 9

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 7

M1 - 722

ER -