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Description
Boron Neutron Capture Therapy (BNCT) is a radiotherapy (RT) technique based on targeting tumors with a $^{10}$B-labelled drug and on irradiating them with neutrons. It exploits the $^{10}$B(n,α)$^{7}$Li capture reaction, whose short-ranged high-LET products enable a localized and enhanced therapeutic effect compared to photon-based RT. Products of other neutron reactions also contribute to the overall absorbed dose imparted to the patient, each with a potentially different radiobiological effectiveness. The $^{14}$N(n,p)$^{14}$C reaction is among the most frequent ones, and produces 583 keV protons. The aim of this study was irradiating U87 cells, from an aggressive and radioresistant glioblastoma cell line, with 583 keV protons, in order to start investigating their radiobiological effectiveness.
Irradiations were conducted at the CIRCE (Center forIsotopic Research on Cultural and Environmental Heritage) Laboratory of University of Campania “Luigi Vanvitelli”, using its Pelletron tandem accelerator to produce the proton beam and a dedicated beamline for radiobiological experiments, consisting in a scattering chamber with several radial channels and a movable target holder [1]. In particular, a gold target and the 15° and 60° channels were employed. Preliminary irradiations with Silicon Surface Barrier Detectors (SSBD) placed at the two angles are conducted for counting calibration, employed for subsequent real-time beam dosimetry. Then, the 15° SSBD is replaced with CR39 nuclear track detectors for dose/fluence verification. Finally, the U87 MG cells, seeded on the mylar basis of cylindrical sample holders in layers of 10 μm nominal thickness, are irradiated at different nominal dose values. The initial beam energy set to have average incident proton energy of 583 keV on the cells was calculated taking into account the energy losses in the gold target and in the mylar layer, by using SRIM/TRIM and GATE/GEANT4 Monte Carlo (MC) simulations. The same simulation toolkits were employed to calculate the average absorbed doses to the cells and compare them with the real-time dosimetry, which follows a LET-based analytical approach [1]. After irradiation, a clonogenic assay of the cells was carried out, estimating the survival fractions (SFs) at the different dose values and deducing the respective survival curve by fitting the data with the linear-quadratic model.
The results of etching and trace counting on CR39 are in good agreement with the theoretical expected fluences. The cellular dosimetric estimates from MC simulations show some discrepancies with respect to the analytical ones, suggesting a possible integration of MC in the the real-time dosimetry workflow for proton beams of the energies employed in this study. The obtained SFs for 583 keV protons, when compared with the ones obtained on the same cell line with 250 kVp x-rays, show higher radiobiological effectiveness. The lack of radiobiological data in literature for protons of such energies warrant further studies, for accurately estimating new survival curves of high interest for BNCT.
References
[1] Ricciardi V. et al. Appl Sci, 2021; 11(24):11986. https://doi.org/10.3390/app112411986
