The production by 72 MeV protons of keV neutrons for 10B neutron capture therapy

Fast neutrons, produced in a spallation process by 72 MeV protons hitting heavy nuclei, can be moderated down to keV energies, suitable for 10B capture therapy. Measurements of neutron flux from copper and lead targets, after moderation by water and hydrocarbons, have been performed, together with measurements of the fast neutron and gamma-backgrounds. The comparisons with Monte Carlo calculations show good agreement. As neutron fluences up to 10(12) to 10(13)n/cm2 can be produced within a few hours in about 0.5 m target distance the technique seems to be suitable for clinical experiments.     

Analysis of neutron and gamma-ray streaming along the maze of NRCAM thallium production target room.

Study of the shield performance of a thallium-203 production target room has been investigated in this work. Neutron and gamma-ray equivalent dose rates at various points of the maze are calculated by simulating the transport of streaming neutrons, and photons using Monte Carlo method. For determination of neutron and gamma-ray source intensities and their energy spectrum, we have applied SRIM 2003 and ALICE91 computer codes to Tl target and its Cu substrate for a 145 microA of 28.5 MeV protons beam. The MCNP/4C code has been applied with neutron source term in mode n p to consider both prompt neutrons and secondary gamma-rays. Then the code is applied for the prompt gamma-rays as the source term. The neutron-flux energy spectrum and equivalent dose rates for neutron and gamma-rays in various positions in the maze have been calculated. It has been found that the deviation between calculated and measured dose values along the maze is less than 20%.     

Analysis of epithermal neutron production by near-threshold (p,n) reactions

A recent advance in portable accelerator neutron source development was research on production of epithermal neutrons by near-threshold charged-particle reactions. When the projectile energy is accurately controlled at an energy close to the reaction threshold, the neutrons produced will have energies less than or around 100 keV and can be used with little or no moderation or filtration in neutron capture therapy. Although the total neutron yield is lower than at higher proton energies, the epithermal neutron flux may be sufficiently intense because of the softer energy spectrum and the requirement for less neutron moderation. This paper presents an analysis of the main characteristics of epithermal neutron production by this method using the Li (p,n) reaction as an example. The energy, yield and angular characteristics of neutron emission are discussed. The achievable epithermal fluxes are computed from experimental data. The results are used to assess the feasibility of near-threshold production of epithermal neutrons for neutron capture therapy with compact accelerators such as a RFQ proton acceelerator. The results indicated that, using a Li₃N target, 1 mA of 2 MeV protons will produce 10⁹ n/cm²/s with an average energy of 83 keV while 5.6 mA of 1.91 MeV protons can produce 10⁹ n/cm²/s with an average energy of 45 keV.     

Detection of fast neutrons from shielded nuclear materials using a semiconductor alpha detector

The response of a semiconductor alpha detector to fast (>1 MeV) neutrons was investigated by using measurements and simulations. A polyethylene converter was placed in front of the detector to register recoil protons generated by elastic collisions between neutrons and hydrogen nuclei of the converter. The developed prototype equipment was tested with shielded radiation sources. The low background of the detector and insensitivity to high-energy gamma rays above 1 MeV are advantages when the detection of neutron-emitting nuclear materials is of importance. In the case of a ²⁵²Cf neutron spectrum, the intrinsic efficiency of fast neutron detection was determined to be 2.5×10⁻⁴, whereas three-fold greater efficiency was obtained for a ²⁴¹AmBe neutron spectrum.     

Benchmark experiments for cyclotron-based neutron source for BNCT.

In the previous study, we found the feasibility of a cyclotron-based BNCT using the Ta(p,n) neutrons at 90 degrees bombarded by 50 MeV protons, and the iron, AlF(3), Al and (6)LiF moderators by simulations using the MCNPX code. In order to validate the simulations to realize the cyclotron-based BNCT, we measured the epithermal neutron energy spectrum passing through the moderators with our new spectrometer consisting of a (3)He gas counter covered with a silicon rubber loaded with (nat)B and polyethylene moderator and the depth distribution of the reaction rates of (197)Au(n,gamma)(198)Au in an acrylic phantom set behind the rear surface of the moderators. The measured results were compared with the calculations using the MCNPX code. We obtained the good agreement between the calculations and measurements within approximately 10% for the neutron energy spectra and within approximately 20% for the depth distribution of the reaction rates of (197)Au(n,gamma)(198)Au in the phantom. The comparison clarified a good accuracy of the calculation of the neutron energy spectrum passing through the moderator and the thermalization in a phantom. These experimental results will be a good benchmark data to evaluate the accuracy of the calculation code.     

BINP accelerator based epithermal neutron source

Innovative facility for neutron capture therapy has been built at BINP. This facility is based on compact vacuum insulation tandem accelerator designed to produce proton current up to 10 mA. Epithermal neutrons are proposed to be generated by 1.915–2.5 MeV protons bombarding a lithium target using ⁷Li(p,n)⁷Be threshold reaction. In the article, diagnostic techniques for proton beam and neutrons developed are described, results of experiments on proton beam transport and neutron generation are shown, discussed, and plans are presented.     

New technical solution for using the time-of-flight technique to measure neutron spectra

New technical solution is proposed for using the time-of-flight technique to measure neutron spectra on VITA-facility. During 200 ns the energy of protons increases from 1.865 up to 1.915 MeV by supplying the square pulse of 50 kV on the neutron-generating target, which is isolated from facility body. During these 200 ns the generation of neutrons is performed. The spectrum can be obtained measuring the time of flight by a remote neutron detector.     

Development of a low-energy monoenergetic neutron source for applications in low-dose radiobiological and radiochemical research

The McMaster University 3 MV KN Van de Graff accelerator facility primarily dedicated to in vivo neutron activation measurements has been used to produce moderate dose rates of monoenergetic fast neutrons of energy ranging from 150 to 600 keV with a small energy spread of about 25 keV (1σ width of Gaussian) by bombarding thin lithium targets with 2.00–2.40 MeV protons. The calculated dose rate of the monoenergetic neutrons produced using thin lithium targets as functions of beam energy, target thickness, lab angle relative to beam direction, and the solid angle subtended by the sample with the target has also been reported.     

硼中子俘获治疗的加速器中子源7Li(p,n)7Be的中子特性研究

目的 通过研究质子加速器 ⁷Li(p,n)⁷Be 反应的中子特性,为研究和制作适用于硼中子俘获治疗(BNCT)的加速器中子源提供基础数据。方法 加速质子使其轰击Li靶后产生中子;通过金属箔活化法,测量中子与In箔发生阈值反应后放出的γ射线;然后计算出In箔的放射性活度、加速器反应后放出中子的注量和反应的微分截面。结果 质子加速轰击Li靶后,在不同方向产生不同能量和注量的中子。加速器电压分别为3.0、2.8和2.6 MV,出射中子与入射质子束的方向一致时, ⁷Li(p,n)⁷Be 反应的微分截面约为50 mb/mr;夹角为60°时,反应的微分截面减小到30 mb/mr左右。由于部分中子与其他金属原子等发生弹性散射而射向后方,提高了这一范围内In箔的比放射性活度,影响了其微分截面的准确性。结论 用金属箔活化法测定中子简便易行,可同时测得多个方向的中子分布,但需对中子与其他金属弹性散射产生的影响进行进一步的研究; ⁷Li(p,n)⁷Be 反应后发射出的中子经慢化后,能得到适于BNCT治疗的热中子和超热中子;若作为BNCT的中子源,加速器的质子束流需达到10 mA。     

Proton beam simulation with MCNPX/CINDER'90: Germanium metal activation estimates below 30MeV relevant to the bulk production of arsenic radioisotopes

Germanium metal targets encapsulated in Nb shells were irradiated in a proton beam. Proton and secondary neutron beam fluences as well as radionuclide activity formation were modeled using MCNPX in combination with CINDER90. Targets were chemically processed using distillation and anion exchange. Good agreement between the measured radiochemical yields and MCNPX/CINDER90 estimates was observed. A target of pentavalent (73,74)As radioarsenic for neutron activation studies was prepared.     

p（35）Be快中子辐射场生物剂量参数的测定

报道了ｐ（３５）Ｂｅ快中子、γ混合辐射场生物剂量参数，说明了采用双电离室方法测量ｐ（３５）Ｂｅ快中子时，剂量计算中有关因子和参数的确定原则和估算结果；给出了辐射场的中子／γ比，照射野内组织比释动能率分布，以及由比释动能率计算小鼠全身与局部照射和血液样品照射时的吸收剂量转换系数等剂量常参数；最后还对剂量测量的误差问题做了分析。     

Hydrogen effects in neutron activation analysis

Perturbations generated in two neutron fields, with different energy distributions, by scattering on hydrogen atoms are reported and discussed, as well as the influence of various parameters. The thermal neutron capture rates of several nuclei can be enhanced by about 18% in solutions in light water as compared to heavy water, for 20 cm³ cylindrical containers. This effect appears to be independent of the initial distribution of the epithermal neutrons, and can be accounted for by the scattering of non-Maxwellian, quasi thermalized neutrons to lower energies. The enhancement ratio is found to be about the same for a variety of nuclei (B, Hg, Gd, Eu, Sm and Cd), in spite of large differences in the variations of their cross sections with neutron energy. This can be explained by assuming that the incoming fluxes present a depression at the level of the Cd resonance, at about 0.18 eV.     

Development of a simple neutron irradiation facility utilizing the stray neutron field of a medical cyclotron

During the routine isotope production schedule at the Australian National Medical Cyclotron thick copper plates, electroplated with enriched target materials, are bombarded with 30 MeV protons with an average beam current of 200 μA. As a result an intense high-energy, prompt neutron flux of the order of 1.72 × 10¹³ neutrons·cm⁻²·2⁻¹ is generated in the immediate vicinity of the target. The stray fast neutrons were moderated using a water-filled PVC bucket placed on the target station. A maximum thermal neutron flux of 3.88 × 10⁹ neutrons·cm⁻²·s⁻¹ was measured in the bucket using cobalt activation discs. The thermal neutrons from this irradiation facility has been used for the neutron activation analysis of trace elements in archaeological artefacts. It has also been planned to utilize the fast neutron flux by varying the geometry of the water moderator in order to estimate oxygen concentration in high-temperature superconductors and aluminium and silicon in ceramics.     

Analysis and comparison of monoenergetic fast neutron fluence determination using 238U samples at different positions with respect to the neutron source

Using two (238)U samples placed in a gridded ionization chamber and a parallel-plate fission chamber, fluence of monoenergetic fast neutrons was determined. Four runs of measurements were performed. Analysis showed that although the neutron fluences for the two (238)U samples differ by 20-33 times in the present work, the fluences at the position of the sample in the gridded ionization chamber determined by the two ways are in agreement within experimental uncertainties.     

Biological intercomparisons of neutron beams used for radiotherapy generated by p(+)-->Be in hospital-based cyclotrons.

The new generation of hospital-based neutron therapy facilities involve cyclotrons using protons on beryllium. The spectrum of neutrons produced includes a large and variable proportion of low-energy neutrons that are poorly penetrating but biologically effective. Cells cultured in vitro were used to compare the three US facilities at Seattle, M.D. Anderson and UCLA, together with the UK facility at Clatterbridge. Cyclotrons were compared within a given experiment on the same day using cells from a common suspension. Among the three US facilities, the relative potency factor at a depth of 25 mm differs by about 11%, with Seattle the least and UCLA the most biologically effective. Clatterbridge was compared directly with M.D. Anderson and found to be less effective by about 5%; it has a slightly lower biological effectiveness than any of the US facilities. There is evidence for an increased biological effectiveness in the build-up region, which reduces the effective skin sparing potential. There is not much difference in build-up between the three US facilities. Using the proton-on-beryllium neutron production process results in a wide spectrum of neutrons with a large but variable low-energy component. The biological effectiveness of the beam depends on target design and thickness as well as the design of the collimating system. Consequently the biological effectiveness of neutron beams generated by this process must be assessed on an individual basis. It cannot be assumed that because cyclotrons have similar accelerating energies that the relative biological effectiveness will be the same.     

Radiobiological studies with therapeutic neutron beams generated by p+ leads to Be or d+ leads to Be

Mammalian cells cultured in vitro were used to study the radiobiological characteristics of neutron beams generated by 43 MeV protons on beryllium or 25 MeV deutrons on beryllium. For an unfiltered beam of neutrons generated by 43 MeV p+ leads to Be the relative biological effectiveness was found to be 8-12% higher at a depth of 2 cm than at a depth of 12 cm due to the presence of a large component of low-energy neutrons. The addition of a hydrogenous filter 4 cm thick preferentially removed the low-energy neutrons from the beam and, as a result, the neutron RBE was independent of depth. There was no significant difference in the oxygen enhancement ratio between the filtered neutrons produced by 43 Mev p+ leads to Be and neutrons produced by 25 MeV d+ leads to Be; for both beams the OER value was about 1.6.     

Neutron flow measurements in the d(14) + Be neutron radiation field from the cyclotron in Essen

It exists the possibility in the neutron therapy of specific tumours to increase the local energy dose in the tumour by treatment with fast neutrons under use of B-10. Thermal neutrons cause the neutron capture reaction B-10(n, alpha)Li-7 in tissue. A sufficiently high number of thermic neutrons is necessary combined with a possibly selective concentration of B-10 in the tumour as target volume for the clinical application. Gold foils were activated in a water phantom at several depths for the quantitative determination of the thermal neutron fluence. A result of this measurements is a maximal thermal neutron fluence of 1.44 X 10(10) cm-2 at depth of 5 cm with applied total energy dose of 0.8 Gy.     

Phantom dosimeters examined by NMR analysis: a promising technique for 3-D determination of absorbed dose

Fricke-infused agarose gels examined by nuclear magnetic resonance (NMR) analysis are inspected, and their response to γ-rays, thermal neutrons and protons, at radiotherapy dose levels, is examined. The gel composition is chosen with attention to the tissue equivalence for the radiation fields of interest; this problem is crucial, in particular, for thermal neutrons. The feasibility of three-dimensional determination of absorbed dose in Fricke-gel phantoms is investigated, and the possibility of employing the technique in conformal therapies, such as boron neutron capture therapy (BNCT) and proton therapy, is tested. Isodose curve determination in a cylindrical gel phantom exposed to thermal neutrons is presented. A method for depth-dose profiling in tissue exposed to protons is described, and some results are reported which show that the depth-dose data are determinable with millimetric precision. Results obtained with a spectrophotometer from gel augmented with a metal indicator are reported and discussed also. These results show the possibility of obtaining a very sensitive dosimetry technique consisting of spectrophotometric analysis of such a Fricke-gel.     

Interaction between the biological effects of high- and low-LET radiation dose components in a mixed field exposure

Abstract

Purpose: The relative biological effectiveness of two epithermal neutron sources, a reactor based source at Studsvik, Sweden, and a proton accelerator-based source in Birmingham, UK, was studied in relation to the proportional absorbed dose distribution as a function of neutron energy. Evidence for any interactions between the effects of biological damage induced by high- and low-linear energy transfer (LET) dose components, in this ‘mixed field’ irradiation, was also examined

Materials and methods: Clonogenic survival in Chinese Hamster-derived V79 cells was used to assess biological effectiveness in this study. Cells were irradiated in suspension at 4°C at depths of 20, 35, 50 and 65 mm in a water phantom. This prevented the repair of sublethal damage, predominantly that produced by both incident and induced γ-rays in the field, over the variable periods of exposure required to irradiate cells with the same total absorbed dose. Cell survival, as a function of the absorbed radiation dose and depth in the phantom, was compared with Monte Carlo N-Particle (MCNP) calculations of the proportional absorbed dose distribution as a function of neutron energy for the two sources.

Results: In terms of the dose-related reduction in clonogenic cell survival, the epithermal neutron source at Studsvik was more biologically effective than the Birmingham source at all depths considered in the phantom. Although the contribution from the high-LET dose component was greater for the Studsvik source at 20 mm depth in the phantom, at greater depths the dose contribution from the high-LET dose component at Studsvik overlap with those for the Birmingham source. However, the most striking difference is in the fast neutron component to the dose of the two sources, neutron energies > 1 MeV were only associated with the Studsvik source. The relative biological effectiveness (RBE) of both sources declined slightly with depth in the phantom, as the total high-LET dose component declined. The maximum source RBE for Studsvik was 2.70 ± 0.50 at 20 mm; reduced to 2.10 ± 0.35 at depths of 50 and 65 mm. The corresponding values for Birmingham were 1.68 ± 0.25 and 1.31 ± 0.19, all values relate only to the surviving fraction of V79 cells at 37%, since RBE values are only applicable to the selected endpoint. Based on a dose reduction factor (DRF) of 1.0 for the total low-LET component to the absorbed dose, the RBE values for the high-LET dose component (fast neutrons and induced protons from the nitrogen capture reaction) was 14.5 and 7.05 for the Studsvik and Birmingham neutron sources, respectively. This is well outside the range of RBE historically reported values for V79 cells for the same level of cell survival for fast neutrons. The calculation of RBE values, based on the proportional absorbed dose distribution as a function of neutron energy, from historical data, and using a RBE of 1.8 for the dose from the nitrogen capture reaction, suggests RBE values for the total high-LET dose component of 3.1–2.8 and 2.5–2.0 for Studsvik and Birmingham, respectively, values again declining with depth in the phantom.

Conclusions: The overall biological effectiveness of the mixed field irradiation from an epithermal neutron sources depends on the composition and quality of the different dose components. The experimentally derived RBE values for the total high-LET dose components in these ‘mixed field’ irradiations are well in excess of historical data for fast neutrons. The difference between the historically expected and the observed RBE values is attributed to the interactions between the damage produced by high- and low-LET radiation.     

Neutrons applications in cancer treatment and in specific diagnostics

The major effect of ionizing radiation in cells is to destroy the ability of cells to divide by damaging their DNA strands. Extensive researches are leading to an understanding that the characteristics of high LET radiations such as fast neutrons and low LET radiations like protons, photons and electrons are different; because of different types of their interactions with tissue. Low LET radiations mostly damage tissue by producing free radicals. Oxygen has an effect of enhancing free radical formation in cells. Indeed hypoxic cells, which exist in malignant tumors, are radio resistant under irradiation with low LET radiations. In contrast, neutron interacts with tissue primarily via nuclear interactions, so its biological effectiveness is not affected on the presence of oxygen. The required dose to kill the same number of cancerous cells by neutrons is about one third in comparison with photons. Clinical reports show that a full course of treatment with neutrons consists of 12 treatment sessions, compared to 30-40 treatments with photons or electrons. In conclusion, in this review we describe which cancers or tumors could be better treated with neutrons. We also refer to whether neutrons could be used for diagnosis.