Dose-Dependent Suppression of Human Glioblastoma Xenograft Growth by Accelerator-Based Boron Neutron Capture Therapy with Simultaneous Use of Two Boron-Containing Compounds

Vladimir Kanygin; Ivan Razumov; Alexander Zaboronok; Evgenii Zavjalov; Aleksandr Kichigin; Olga Solovieva; Alphiya Tsygankova; Tatiana Guselnikova; Dmitrii Kasatov; Tatiana Sycheva; Bryan J Mathis; Sergey Taskaev

doi:10.3390/biology10111124

Dose-Dependent Suppression of Human Glioblastoma Xenograft Growth by Accelerator-Based Boron Neutron Capture Therapy with Simultaneous Use of Two Boron-Containing Compounds

Biology (Basel). 2021 Nov 2;10(11):1124. doi: 10.3390/biology10111124.

Authors

Vladimir Kanygin¹, Ivan Razumov^{1

2}, Alexander Zaboronok^{1

3}, Evgenii Zavjalov^{1

2}, Aleksandr Kichigin¹, Olga Solovieva^{1

2}, Alphiya Tsygankova^{1

4}, Tatiana Guselnikova^{1

4}, Dmitrii Kasatov^{1

5}, Tatiana Sycheva⁵, Bryan J Mathis⁶, Sergey Taskaev^{5

7}

Affiliations

¹ Laboratory of Medical and Biological Problems of BNCT, Novosibirsk State University, 1 Pirogov Str., 630090 Novosibirsk, Russia.
² Center for Genetic Resources of Laboratory Animals, Institute of Cytology and Genetics SB RAS, 10, Acad. Lavrentieva Ave., 630090 Novosibirsk, Russia.
³ Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan.
⁴ Nikolaev Institute of Inorganic Chemistry SB RAS, 3, Acad. Lavrentieva Ave., 630090 Novosibirsk, Russia.
⁵ Budker Institute of Nuclear Physics, Siberian Branch of Russian Academy of Sciences, 11, Acad. Lavrentieva Ave., 630090 Novosibirsk, Russia.
⁶ International Medical Center, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba 305-8576, Ibaraki, Japan.
⁷ Laboratory of BNCT, Novosibirsk State University, 1 Pirogov Str., 630090 Novosibirsk, Russia.

Abstract

(1) Background: Developments in accelerator-based neutron sources moved boron neutron capture therapy (BNCT) to the next phase, where new neutron radiation parameters had to be studied for the treatment of cancers, including brain tumors. We aimed to further improve accelerator-BNCT efficacy by optimizing dosimetry control, beam parameters, and combinations of boronophenylalanine (BPA) and sodium borocaptate (BSH) administration in U87MG xenograft-bearing immunodeficient mice with two different tumor locations. (2) Methods: The study included two sets of experiments. In Experiment #1, BPA only and single or double irradiation in higher doses were used, while, in Experiment #2, BPA and BSH combinations and single or double irradiation with dosage adjustment were analyzed. Mice without treatment or irradiation after BPA or BPA+BSH injection were used as controls. (3) Results: Irradiation parameter adjustment and BPA and BSH combination led to 80-83% tumor-growth inhibition index scores, irradiation:BNCT ratios of 1:2, and increases in animal life expectancy from 9 to 107 days. (4) Conclusions: Adjustments in dosimetry control, calculation of irradiation doses, and combined use of two ¹⁰B compounds allowed for BNCT optimization that will be useful in the development of clinical-trial protocols for accelerator-based BNCT.

Keywords: accelerator-based neutron source; animal tumor model; boron compounds; boron neutron capture therapy; boronophenylalanine; glioblastoma; sodium borocaptate.

Abstract

Grants and funding