Abstract
Boron neutron capture therapy (BNCT) is an anticancer modality realized through 10B 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−2s−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.
Highlights
Boron neutron capture therapy (BNCT) is a binary technology relying on selective boron-10 isotope (10 B) accumulation in tumor cells (≥20 μg/g of tumor tissue) to release tumoricidal high linear energy transfer alpha particles and lithium (7 Li) ions intracellularly upon irradiation with epithermal neutrons (Figure S1) [1,2,3]
The short pha-particle pathway during BNCT (~10μm) that remains within the tumor cell diameter alpha-particle pathway during BNCT (~10μm) that remains within the tumor cell diameter and spares normal cells from radiation limits dosimetry options, as there is no essenand spares normal cells from radiation limits dosimetry options, as there is no essential tial extracellular energy release and calculating the boron-related absorbed is diffiextracellular energy release and calculating the boron-related absorbed dose is dose difficult
The cross sections of these processes are different and, for the BNCT spectrum of neutrons, this leads to a small dependence of k on the depth h, which we considered in creating the formula
Summary
Boron neutron capture therapy (BNCT) is a binary technology relying on selective boron-10 isotope (10 B) accumulation in tumor cells (≥20 μg/g of tumor tissue) to release tumoricidal high linear energy transfer (high-LET) alpha particles and lithium (7 Li) ions intracellularly upon irradiation with epithermal neutrons (Figure S1) [1,2,3]. This method, developed to treat invasive incurable cancers such as glioblastoma, malignant melanoma, Pharmaceutics 2021, 13, 1490. The short pha-particle pathway during BNCT (~10μm) that remains within the tumor cell diameter alpha-particle pathway during BNCT (~10μm) that remains within the tumor cell diameter and spares normal cells from radiation limits dosimetry options, as there is no essenand spares normal cells from radiation limits dosimetry options, as there is no essential tial extracellular energy release and calculating the boron-related absorbed is diffiextracellular energy release and calculating the boron-related absorbed dose is dose difficult
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