TY - JOUR

T1 - Gold nanoparticles permit in situ absorbed dose evaluation in boron neutron capture therapy for malignant tumors

AU - Zaboronok, Alexander

AU - Taskaev, Sergey

AU - Volkova, Olga

AU - Mechetina, Ludmila

AU - Kasatova, Anna

AU - Sycheva, Tatiana

AU - Nakai, Kei

AU - Kasatov, Dmitrii

AU - Makarov, Aleksandr

AU - Kolesnikov, Iaroslav

AU - Shchudlo, Ivan

AU - Bykov, Timofey

AU - Sokolova, Evgeniia

AU - Koshkarev, Alexey

AU - Kanygin, Vladimir

AU - Kichigin, Aleksandr

AU - Mathis, Bryan J.

AU - Ishikawa, Eiichi

AU - Matsumura, Akira

N1 - Funding Information: Funding: This work was supported by Grants-in-Aid for Scientific Research (C) JSPS KAKENHI [20K07672] and (B) [18H02909] from the Japanese Ministry of Education, Culture, Sports, Science and Technology. Neutron generation study was supported by the Russian Science Foundation (project no. 19-72-30005). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/9/16

Y1 - 2021/9/16

N2 - Boron neutron capture therapy (BNCT) is an anticancer modality realized through10 B accumulation in tumor cells, neutron irradiation of the tumor, and decay of boron atoms with the release of alpha-particles and lithium nuclei that damage tumor cell DNA. As high-LET particle release takes place inside tumor cells absorbed dose calculations are difficult, since no essential extracellular energy is emitted. We placed gold nanoparticles inside tumor cells saturated with boron to more accurately measure the absorbed dose. T98G cells accumulated ~50 nm gold nanoparticles (AuNPs, 50 µg gold/mL) and boron-phenylalanine (BPA, 10, 20, 40 µg boron-10/mL), and were irradiated with a neutron flux of 3 × 108 cm−2 s−1 . Gamma-rays (411 keV) emitted by AuNPs in the cells were measured by a spectrometer and the absorbed dose was calculated using the formula D = (k × N × n)/m, where D was the absorbed dose (GyE), k—depth-related irradiation coefficient, N—number of activated gold atoms, n—boron concentration (ppm), and m—the mass of gold (g). Cell survival curves were fit to the linear-quadratic (LQ) model. We found no influence from the presence of the AuNPs on BNCT efficiency. Our approach will lead to further development of combined boron and high-Z element-containing compounds, and to further adaptation of isotope scanning for BNCT dosimetry.

AB - Boron neutron capture therapy (BNCT) is an anticancer modality realized through10 B accumulation in tumor cells, neutron irradiation of the tumor, and decay of boron atoms with the release of alpha-particles and lithium nuclei that damage tumor cell DNA. As high-LET particle release takes place inside tumor cells absorbed dose calculations are difficult, since no essential extracellular energy is emitted. We placed gold nanoparticles inside tumor cells saturated with boron to more accurately measure the absorbed dose. T98G cells accumulated ~50 nm gold nanoparticles (AuNPs, 50 µg gold/mL) and boron-phenylalanine (BPA, 10, 20, 40 µg boron-10/mL), and were irradiated with a neutron flux of 3 × 108 cm−2 s−1 . Gamma-rays (411 keV) emitted by AuNPs in the cells were measured by a spectrometer and the absorbed dose was calculated using the formula D = (k × N × n)/m, where D was the absorbed dose (GyE), k—depth-related irradiation coefficient, N—number of activated gold atoms, n—boron concentration (ppm), and m—the mass of gold (g). Cell survival curves were fit to the linear-quadratic (LQ) model. We found no influence from the presence of the AuNPs on BNCT efficiency. Our approach will lead to further development of combined boron and high-Z element-containing compounds, and to further adaptation of isotope scanning for BNCT dosimetry.

KW - Absorbed dose

KW - Accelerator-based neutron source

KW - Boron neutron capture therapy

KW - Dosimetry

KW - Gold nanoparticles

UR - http://www.scopus.com/inward/record.url?scp=85115348647&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics13091490

DO - 10.3390/pharmaceutics13091490

M3 - Article

C2 - 34575566

AN - SCOPUS:85115348647

VL - 13

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 9

M1 - 1490

ER -