BNCT Applications Research Articles

Synthesis and Characterization of Gd-Functionalized B4C Nanoparticles for BNCT Applications

Inorganic nanoparticles of boron-rich compounds represent an attractive alternative to boron-containing molecules, such as boronophenylalanine or boranes, for BNCT applications. This work describes the synthesis and biological activity of multifunctional boron carbide nanoparticles stabilized with polyacrylic acid (PAA) and a gadolinium (Gd)-rich solid phase. A fluorophore (DiI) was included in the PAA functionalization, allowing the confocal microscopy imaging of the nanoparticles. Analysis of the interaction and activity of these fluorescent Gd-containing B4C nanoparticles (FGdBNPs) with cultured cells was appraised using an innovative correlative microscopy approach combining intracellular neutron autoradiography, confocal, and SEM imaging. This new approach allows visualizing the cells, the FGdBNP, and the events deriving from the nuclear process in the same image. Quantification of 10B by neutron autoradiography in cells treated with FGdBNPs confirmed a significant accumulation of NPs with low levels of cellular toxicity. These results suggest that these NPs might represent a valuable tool for achieving a high boron concentration in tumoral cells.

Neutron Beam Characterization on the Beam Tubes of 30 MW G.A. Siwabessy Reactor Using Monte Carlo

The neutron beam characterization had been conducted on six tubes of RSG-GAS reactor for BNCT application in a simulation using Monte Carlo method with MCNP computer code. The simulation was conducted by modeling the geometry and material of RSG-GAS reactor with a model of radiation source from 235U fission reaction in 40 fuel bundles type U3Si2Al with 235U levels of 19.75%. The distribution of neutron and gamma fluxes was simulated from the reactor core to the edge of beam tube of S1, S2, S3, S4, S5, and S6 with a tube length of 400 cm and a diameter of 30 cm. The highest neutron flux produced by the beam tube of S5 was 4.3×1010 cm−2s−1 with the highest gamma dose was 1362 Sv/j. The lowest neutron flux produced by the beam tube of S6 was 5.9×109 cm−2s−1 with a gamma dose was 51 Sv/j. Based on the characterization result, it was shown that the output neutron beam of each RSG-GAS beam tube had the potential to be used for many application.

Simulation of absorbed doses distribution in a polyethylene phantom for BNCT application at the Dalat research reactor

In this paper, the distribution of absorbed dose components in a polyethylene phantom for BNCT application at Dalat Nuclear Research Reactor (DNRR) were calculated using the MCNP5 code. The configuration of horizontal neutron channel No.2 of the DNRR, which contains a cylindrical collimator with neutron filters of 20-cm Si and 3-cm Bi, was simulated. The results show that the gamma dose along the central axis of the phantom has the maximum value of 1.82×10-6 Gy at the 0.5-cm depth, and reduces to 9.05×10-7 Gy at the 3-cm depth. The main contribution to gamma dose is due to the interaction of thermal neutron with hydrogen in the phantom via the 1H(n,γ)2H reaction, and its value is much smaller than thermal neutron dose. The total absorbed dose along the central axis of the phantom has the maximum value of 7.87×10-5 Gy at the 0.5-cm depth, and decreases rapidly to 1.52×10-5 Gy at the 3-cm position, and mainly depends on the boron and thermal neutron doses caused by the 10B(n, α)7Li and 14N(n, p)14C reactions, respectively.

Feasibility study of using IRT-T research reactor for BNCT applications

This paper presents the results of neutron and gamma calculations aimed at assessing the feasibility of creating an installation for performing research in the field of NСT at the research reactor IRT-T. Considered aspects of choosing a suitable experimental channel as the basis for the installation being created. The calculation results of possible ways of outlet beam parameters improvement consist of inserting of reflector in channel, BSA with filters and collimator are shown.

Rockwell Hardness Testing of Pure Nickel Collimators for BNCT Application

In this study, Rockwell and Brinell hardness testing was used to examine material hardness. These methods were chosen because they are easy to carry out, relatively inexpensive, and almost all sizes and shapes can be tested, in which nickel hardness before and after centrifugal casting are identified and compared. These tests enable the determination of the hardness numbers of nickel collimators using for boron neutron capture therapy. The samples were five nickel plates with a dimension of 4.5 × 4.5 cm and five collimators. The collimators were cylindrical and made using centrifugal casting. The basic principle of the hardness test was to apply loading on the object being tested. The Rockwell test was used to assess the material's hardness from the difference of indentation depth, while the Brinell test was used to determine the hardness from the diameter of indentation. From the results of this test, the hardness number of nickel before centrifugal casting is 168.53 BHN or 86.13 HRB, while the hardness number after centrifugal casting is 115.68 BHN or 64.84 HRB. It can therefore be concluded that centrifugal casting decreased nickel hardness.

EP-1436: A newly designed water-equivalent bolus technique enables BNCT application to skin tumor

EP-1436: A newly designed water-equivalent bolus technique enables BNCT application to skin tumor

The treatment of metastatic prostate carcinoma with BNCT in the ITU TRIGA MARKII reactor on rat model

Objective: The delivery of curative radiotherapy is commonly has the potential of serious side effects. These side effects still remain dose-limiting factor for external beam radiotherapy and as also curative treatment of prostate cancer (PCa). New treatment alternatives, such as BNCT, are investigated to eliminate these limitations and to improve the therapeutic efficiency of radiation on tumour cells including prostate cancer. In this study, we investigated the efficiency of BNCT application by using our novel 10 B carrier that was called as 10 B-DG on PCa using an in vivo mouse xenograft model. Material and Methods: PCa bearing Copenhagen rats (CRs) were used in this experimental animal study. A total of 12 CRs at the age of 2 months were used in this experimental animal study. MAT-LyLu PCa cells were injected subcutaneously into the peritoneal cavity of rats to create PCa model. The samples were divided into 4 groups: As, control, neutron irradiated, 10 B-DG and 10 B-DG + neutron irradiated group. 10 BDG was administrated to tumour bearing rats and rats were exposed to 8.074 gy/hr thermal and epithermal. Tumour sizes were regularly measured by microtome and PET scan along 20 days. Results: The results have shown that the tumor growth were regressed just in 10 B-DG + neutron irradiated group. In addition that, PET-CT scan results revealed that 18FDG uptake was stopped in the BNCT treated group due to metabolic inactivation of ablated tumor tisue. Conclusion: This study revealed that BNCT treatment can be successfully performed by using our novel 10 B carrier 10 BDG in the management of PCa. We suppose that this novel 10 B carrier can take place as a safe and effective agent in routine clinical practice of BNCT.

Design Collimator and Dosimetry of in Vitro and in Vivo Test Using MCNP-X Code

Studies were carried out to collimator modelling and dosimetry BNCT of in vitro and in vivo test using MCNP-X code. Collimator modelling performed to obtain neutron beam as required by the International Atomic Energy Agency (IAEA). Dosimetry calculations performed to obtain the results of the dose calculation (dosimetry) in the application of BNCT. Collimator modelling and dosimetry simulations performed with MCNPX program. Neutron sources used for simulation, namely cyclotrons HM-30, energy 30 MeV, the current is 1.1 mA. Collimator modelling utilizes to program MCNPX covers cells target as beryllium, collimator wall (reflector), moderate, filter, gamma-ray shielding, and aperture. The simulation results of the modelling are Φ<sub>epi </sub>1.02241x10<sup>10</sup> n/cm2 s, D<sub>f</sub>/Φ<sub>epi </sub>2.36487x10<sup>-11 </sup>Gy-cm<sup>2</sup>/n, D<sub>γ</sub>/Φ<sub>epi</sub> 4.68416x10<sup>-12</sup> Gy-cm<sup>2</sup>/n, Φ<sub>th</sub>/Φ<sub>epi </sub>3.76285x10<sup>-01</sup>, J/Φ<sub>epi </sub>8.37678x10<sup>3</sup>. Based on the calculation of the dose rate that has been done, the result that the optimal dose rate at a depth of 1cm.

Basic Principle Application and Technology of Boron Neutron Capture Cancer Therapy (BNCT) Utilizing Monte Carlo N Particle 5’S Software (MCNP 5) with Compact Neutron Generator (CNG)

The purpose are to know basic principle, needed component, types of compact neutron generator, plus and minus CNG, identify materials can use as collimator, know physics parameters as input software MCNP 5, knowing step simulation with software MCNP 5, dose in BNCT, knowing boron compound that use in BNCT, getting collimator design for BNCT'S application with source is compact neutron generator and count physics parameter of collimator output and compares it with standard IAEA. Method are reading reference and simulation with MCNP 5. The result are BNCT use high linear energy transfer from alpha and lithium as a result of <sup>10</sup>B(n,α)<sup>7</sup>Li reaction. BNCT method is effective for cancer therapy. It is not dangerous to normal tissues. To work perfectly, BNCT needs neutron, boron (BSH and BPA as boron compound) Indonesia have study turmeric as boron compound, neutron source, collimator and dose. Dose component in BNCT that important are dose of recoil proton, dose of gamma, dose alfa and dose radiation to environmentally. CNG produce neutron with fussion reaction of deuterium-deuterium (2,45 MeV), deuterium-tritium (14 MeV), tritium-tritium(11,31 MeV) can used as neutron source BNCT. Many kinds of CNG are axial, coaxial, toroidal, plasma design, accelerator design, and CNG with diameter 2,5 cm. CNG have more benefit than another neutron source, make CNG compatible as BNCT application. Neutron from CNG need collimator to get neutron as IAEA’s parameter. Material for collimator are wall and aperture (material: Ni, Pb, Bi), moderator (Al, Al<sub>2</sub>O<sub>3, </sub>S, AlF<sub>3</sub>), filter (<sup>6</sup>Li,<sup>10</sup>B, LiF, Al, Cd-nat,<sup> </sup>Ni-60, BiF<sub>3</sub>, <sup>157</sup>Gd, <sup>151</sup>Eu), gamma shield (Bi, Pb). Simulation using MCNP 5 has severally steps, the first is sketching problem, the second is making listing program with notepad, the third open program on visual editor, and the last is running program. Acquired result is design tube collimator with radius 71 cm and high 139, 5 cm. Design contained on lead wall as thick as 19, 5 cm; moderate: heavy water as thick as 4 cm, AlF<sub>3 </sub>girdle a half of part CNG, MgF <sub>2 </sub>(19 cm + 10 cm), Al (6,5 cm + 5 cm);Gamma shield: bismuth, and aperture with diameter 6 cm by steps aside nickel. The result collimator output cross three of five IAEA'S defaults. They are the ratio among dosed gamma with flux epithermal is 5,738×10 <sup>-24</sup>Gy. cm <sup>2 </sup>.n <sup>-</sup>1, the value of ratio among thermal's neutron flux with epithermal neutron is 0, 02567, and ratio among current with flux neutron completely is 1, 2. Need considerable effort of all part to realize BNCT in Indonesia.

Reprint of Application of BNCT to the treatment of HER2+ breast cancer recurrences: Research and developments in Argentina

In the frame of the Argentine BNCT Project a new research line has been started to study the application of BNCT to the treatment of locoregional recurrences of HER2+ breast cancer subtype. Based on former studies, the strategy considers the use of immunoliposomes as boron carriers nanovehicles to target HER2 overexpressing cells. The essential concerns of the current stage of this proposal are the development of carriers that can improve the efficiency of delivery of boron compounds and the dosimetric assessment of treatment feasibility. For this purpose, an specific pool of clinical cases that can benefit from this application was determined. In this work, we present the proposal and the advances related to the different stages of current research.

Liquid Li based neutron source for BNCT and science application

Liquid lithium (Li) is a candidate material for a target of intense neutron source, heat transfer medium in space engines and charges stripper. For a medical application of BNCT, epithermal neutrons with least energetic neutrons and γ-ray are required so as to avoid unnecessary doses to a patient. This is enabled by lithium target irradiated by protons at 2.5MeV range, with utilizing the threshold reaction of 7Li(p,n)7Be at 1.88MeV. In the system, protons at 2.5MeV penetrate into Li layer by 0.25mm with dissipating heat load near the surface. To handle it, thin film flow of high velocity is important for stable operation. For the proton accelerator, electrostatic type of the Schnkel or the tandem is planned to be employed. Neutrons generated at 0.6MeV are gently moderated to epithermal energy while suppressing accompanying γ-ray minimum by the dedicated moderator assembly.

Application of BNCT to the treatment of HER2+ breast cancer recurrences: Research and developments in Argentina

In the frame of the Argentine BNCT Project a new research line has been started to study the application of BNCT to the treatment of locoregional recurrences of HER2+ breast cancer subtype. Based on former studies, the strategy considers the use of immunoliposomes as boron carriers nanovehicles to target HER2 overexpressing cells. The essential concerns of the current stage of this proposal are the development of carriers that can improve the efficiency of delivery of boron compounds and the dosimetric assessment of treatment feasibility. For this purpose, an specific pool of clinical cases that can benefit from this application was determined. In this work, we present the proposal and the advances related to the different stages of current research.

Modification of the radial beam port of ITU TRIGA Mark II research reactor for BNCT applications

This paper aims to describe the modification of the radial beam port of ITU (İstanbul Technical University) TRIGA Mark II research reactor for BNCT applications. Radial beam port is modified with Polyethylene and Cerrobend collimators. Neutron flux values are measured by neutron activation analysis (Au–Cd foils). Experimental results are verified with Monte Carlo results. The results of neutron/photon spectrum, thermal/epithermal neutron flux, fast group photon fluence and change of the neutron fluxes with the beam port length are presented.

Short and long-term exposure of CNS cell lines to BPA-f a radiosensitizer for Boron Neutron Capture Therapy: safety dose evaluation by a battery of cytotoxicity tests

Despite the current clinical use of boronophenylalanine-fructose (BPA-f), as radiosensitizer, in BNCT application for brain tumors, still remains to be determined the safety dose of this agent. We evaluated the potential risk of primary BPA-f toxicity before neutronic irradiation at different concentrations (0–100μgBeq/ml) after short- and long-term exposure (4–48h and 7–10 days), using a battery of tests (i.e. MTT assay, calcein-AM/Propidium Iodide staining, clonogenic test) in CNS cell models (D384 and SH-SY5Y), and non-neuronal primary human fibroblasts (F26). MTT data showed: (i) no cytotoxic effects after short-term exposure (4h) to any of BPA-f concentrations tested in all cell models; (ii) dose- and time-dependent mitochondrial activity impairment in D384 and SH-SY5Y cells only (with 60% and 40% cell death in D384 and SH-SY5Y, respectively, after 48h exposure to BPA-f 100μgBeq/ml). By Calcein-AM/PI staining, BPA-f treatment was specific toward SH-SY5Y cells only: a dose-dependent cell density reduction was observed, with a more pronounced effect after 48h exposure (15–40% at doses ranging 20–100μgBeq/ml). Clonogenic data revealed dose-dependent decrease of cell proliferative capacity in all cell lines, still the SH-SY5Y cells were the most sensitive ones: the lowest dose (20μgBeq/ml) produced 90% cell decrease. These results indicate dose- and time-dependent cytotoxic effects of BPA-f, with CNS cells showing a lower tolerance compared to fibroblasts. Long-term exposure to BPA-f compromised the proliferative capacity regardless of cell model type (cell sensitivity being SH-SY5Y>D384>F26). In short-time exposure, BPA-f exhibits a safe dosage up to 40μgBeq/ml for the viability of CNS cell lines.

Photoneutron production by a 25 MeV electron linac for BNCT application

Recently, extensive research has been performed to produce neutron beams in hospitals using electron linear accelerator for neutron medical applications such as Boron Neutron Capture Therapy. In this article, we present the results of Monte Carlo calculations, using MCNPX code, for the possibility of setting up a 25MeV electron linac based photoneutron source for BNCT applications. Photon and photoneutron converters with different materials in various geometries were studied to achieve maximum neutron yield. In addition, the possibility of using an optimized neutron beam in BNCT was investigated by proposing the optimized beam shaping assembly. It was shown that our designed neutron beam, which passes through the optimized BSA, meets the IAEA criteria for in-air parameters.

Dose determination using alanine detectors in a mixed neutron and gamma field for boron neutron capture therapy of liver malignancies

Boron Neutron Capture Therapy for liver malignancies is being investigated at the University of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and may be suitable for measurements in mixed neutron and gamma fields. Material and methods. Two experiments have been carried out in the thermal column of the TRIGA Mark II reactor at the University of Mainz. Alanine dosimeters have been irradiated in a phantom and in liver tissue. Results. For the interpretation and prediction of the dose for each pellet, beside the results of the measurements, calculations with the Monte Carlo code FLUKA are presented here. For the phantom, as well as for the liver tissue, the measured and calculated dose and flux values are in good agreement. Discussion. Alanine dosimeters, in combination with flux measurements and Monte Carlo calculations with FLUKA, suggest that it is possible to establish a system for monitoring the dose in a mixed neutron and gamma field for BNCT and other applications in radiotherapy.

Design, development and characterization of multi-functionalized gold nanoparticles for biodetection and targeted boron delivery in BNCT applications

The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coated with multilayers of polyelectrolytes functionalized with the fluorescent dye (FITC), boronophenylalanine and folic acid. In vitro confocal fluorescence microscopy demonstrated significant uptake of the nanoparticles in cancer cells that are known to overexpress folate receptors.

The radiobiological principles of boron neutron capture therapy: A critical review

The radiobiology of the dose components in a BNCT exposure is examined. The effect of exposure time in determining the biological effectiveness of γ-rays, due to the repair of sublethal damage, has been largely overlooked in the application of BNCT. Recoil protons from fast neutrons vary in their relative biological effectiveness (RBE) as a function of energy and tissue endpoint. Thus the energy spectrum of a beam will influence the RBE of this dose component. Protons from the neutron capture reaction in nitrogen have not been studied but in practice protons from nitrogen capture have been combined with the recoil proton contribution into a total proton dose. The relative biological effectiveness of the products of the neutron capture reaction in boron is derived from two factors, the RBE of the short range particles and the bio-distribution of boron, referred to collectively as the compound biological effectiveness factor. Caution is needed in the application of these factors for different normal tissues and tumors.

Fission reactor based epithermal neutron irradiation facilities for routine clinical application in BNCT—Hatanaka memorial lecture

Based on experience gained in the recent clinical studies at MIT/Harvard, the desirable characteristics of epithermal neutron irradiation facilities for eventual routine clinical BNCT are suggested. A discussion of two approaches to using fission reactors for epithermal neutron BNCT is provided. This is followed by specific suggestions for the performance and features needed for high throughput clinical BNCT. An example of a current state-of-the-art, reactor based facility, suited for routine clinical use is discussed. Some comments are provided on the current status of reactor versus accelerator based epithermal neutron sources for BNCT. This paper concludes with a summary and a few personal observations on BNCT by the author.

On accelerator-based neutron sources and neutron field characterization with low energy neutron spectrometer based on position sensitive 3He counter

The development of new neutron sources for BNCT applications, based on particle accelerators is currently underway all over the world. Though nuclear reactors were used for a long time as the only neutron source available having the requested flux levels, the accelerator-based ones have recently been investigated on the other hand due to its easy-to-use and acceptable performances. However, when using an accelerator, various secondary particles would be emitted which forms a troublesome background. Moreover, the neutrons produced have usually an energy spectrum somewhat different from the requested one and thus should be largely moderated. An additional issue to be taken into account is the patient positioning, which should be close to the neutron source, in order to take advantage of a neutron flux level high enough to limit the BNCT treatment time within 1 h. This implies that, inside a relatively narrow space, neutrons should be moderated, while unnecessary secondary particles should be shielded. Considering that a background-free neutron field from an accelerator-driven neutron source dedicated to BNCT application is generally difficult to be provided, the characterization of such a neutron field will have to be clearly assessed. In the present study, a low energy neutron spectrometer has been thus designed and is now being developed to measure the accelerator-based neutron source performance. The presently proposed spectrometer is based on a 3He proportional counter, which is 50 cm long and 5 cm in diameter, with a gas pressure of 0.5 MPa. It is quite unique that the spectrometer is set up in parallel with the incident neutron beam and a reaction depth distribution is measured by it as a position sensitive detector. Recently, a prototype detector has been developed and the signal test is now underway. In this paper, the feature of the accelerator-based neutron sources is outlined and importance of neutron field characterization is discussed. And the developed new low energy neutron spectrometer for the characterization is detailed.