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PubMed1998

Combined use of FLUKA and MCNP-4A for the Monte Carlo simulation of the dosimetry of 10B neutron capture enhancement of fast neutron irradiations.

Boron neutron capture enhancement (BNCE) of the fast neutron irradiations use thermal neutrons produced in depth of the tissues to generate neutron capture reactions on 10B within tumor cells. The dose enhancement is correlated to the 10B concentration and to thermal neutron flux measured in the depth of the tissues, and in this paper we demonstrate the feasibility of Monte Carlo simulation to study the dosimetry of BNCE. The charged particle FLUKA code has been used to calculate the primary neutron yield from the beryllium target, while MCNP-4A has been used for the transport of these neutrons in the geometry of the Biomedical Cyclotron of Nice. The fast neutron spectrum and dose deposition, the thermal flux and thermal neutron spectrum in depth of a Plexiglas phantom has been calculated. The thermal neutron flux has been compared with experimental results determined with calibrated thermoluminescent dosimeters (TLD-600 and TLD-700, respectively, doped with 6Li or 7Li). The theoretical results were in good agreement with the experimental results: the thermal neutron flux was calculated at 10.3 X 10(6) n/cm2 s1 and measured at 9.42 X 10(6) n/cm2 s1 at 4 cm depth of the phantom and with a 10 cm X 10 cm irradiation field. For fast neutron dose deposition the calculated and experimental curves have the same slope but different shape: only the experimental curve shows a maximum at 2.27 cm depth corresponding to the build-up. The difference is due to the Monte Carlo simulation which does not follow the secondary particles. Finally, a dose enhancement of, respectively, 4.6% and 10.4% are found for 10 cm X 10 cm or 20 cm X 20 cm fields, provided that 100 micrograms/g of 10B is loaded in the tissues. It is anticipated that this calculation method may be used to improve BNCE of fast neutron irradiations through collimation modifications.

Biophysical Phenomena↗
PubMed1983

Oncogenic transformation of C3H/10T1/2 cells by X-rays, fast-fission neutrons, and cyclotron-produced neutrons.

Lethality and oncogenic transformation were measured in C3H/10T1/2 murine fibroblasts exposed to neutrons and X-rays at doses between 0.5 and 11 Gy. Transformation results with X-rays and low-energy, reactor-produced neutrons were used as a baseline to compare and evaluate the results obtained with high-energy, cyclotron-produced neutrons. The radiations were 100-kVp X-rays at 0.49 Gy min-1, reactor fission neutrons at 0.10 to 0.31 Gy min-1 with an 8 to 20 per cent gamma dose component, and cyclotron-produced neutrons at 0.51 Gy min-1 with mean energy 38 MeV and an 8 per cent gamma dose component. The radiobiological effectiveness (r.b.e.) for cell lethality was 2.4 +/- 0.2 for fission neutrons and 1.7 +/- 0.1 for high-energy neutrons. The maximum proportions of transformants per thousand surviving cells were, respectively, 3.7 +/- 0.8, 6.5 +/- 0.7, and 2.3 +/- 0.6 for X-rays, fission neutrons, and cyclotron-produced neutrons. The maximum observed r.b.e. for transformation induction was 3.8 for fission neutrons and 1.2 for cyclotron neutrons. Thus, high-energy neutrons exhibit a higher r.b.e. for cell killing capacity than for oncogenic transformation in C3H/10T1/2 cells.

Animals↗
PubMed1996

Comet assay study of DNA damage and repair of tumour cells following boron neutron capture irradiation with fast d(14) + Be neutrons.

We compared the amount of radiation-induced DNA damage and the extent of DNA repair in human melanoma cells (MeWo) using the 'comet assay' after neutron, boron neutron capture and X-irradiation. Using a colony-forming assay it was shown earlier that lethal effects in tumour cells treated with fast neutrons may be increased by the neutron capture reaction 10B(n, alpha)7Li. The effectiveness of boron neutron capture in killing tumour cells depends on the number of 10B atoms delivered to the tumour, the subcellular distribution of 10B and the thermal neutron fluence at the side of the tumour. Using the 'comet assay' the DNA damage of fast neutrons (mean energy 5.8 MeV) was shown to be significantly greater than for the same absorbed dose of X-rays. The presence of 600 ppm 10B (boric acid H5 10BO3) in the cell medium during irradiation with d(14) + Be neutrons in a phantom enhances the DNA damage by 20% compared with neutron irradiation alone. After DNA damage induction by neutrons and neutron capture of boron, the DNA repair capacity of the MeWo cells is significantly reduced in comparison with X-irradiation resulting in proportionally more residual DNA damage after 180 min of repair time.

Boron Neutron Capture Therapy↗
PubMed2002

Thermal neutron equivalent dose assessment around the KFUPM neutron source storage area using NTDs. King Fahd University of Petroleum and Minerals.

Area passive neutron dosemeters based on nuclear track detectors (NTDs) have been used for 13 days to assess accumulated low doses of thermal neutrons around neutron source storage area of the King Fahd University of Petroleum and Minerals (KFUPM). Moreover, the aim of this study is to check the effectiveness of shielding of the storage area. NTDs were mounted with the boron converter on their surface as one compressed unit. The converter is a lithium tetraborate (Li2B4O7) layer for thermal neutron detection via 10B(n,alpha)7Li and 6Li(n,alpha)3H nuclear reactions. The area passive dosemeters were installed on 26 different locations around the source storage area and adjacent rooms. The calibration factor for NTD-based area passive neutron dosemeters was found to be 8.3 alpha tracks x cm(-2) x microSv(-1) using active snoopy neutron dosemeters in the KFUPM neutron irradiation facility. The results show the variation of accumulated dose with locations around the storage area. The range of dose rates varied from as low as 40 nSvx h(-1) up to 11 microSv x h(-1). The study indicates that the area passive neutron dosemeter was able to detect accumulated doses as low as 40 nSv x h(-1), which could not be detected with the available active neutron dosemeters. The results of the study also indicate that an additional shielding is required to bring the dose rates down to background level. The present investigation suggests extending this study to find the contribution of doses from fast neutrons around the neutron source storage area using NTDs through proton recoil. The significance of this passive technique is that it is highly sensitive and does not require any electronics or power supplies, as is the case in active systems.

Fast Neutrons↗
PubMed1994

Mixed field dosimetry of epithermal neutron beams for boron neutron capture therapy at the MITR-II research reactor.

During the past several years, there has been growing interest in Boron Neutron Capture Therapy (BNCT) using epithermal neutron beams. The dosimetry of these beams is challenging. The incident beam is comprised mostly of epithermal neutrons, but there is some contamination from photons and fast neutrons. Within the patient, the neutron spectrum changes rapidly as the incident epithermal neutrons scatter and thermalize, and a photon field is generated from neutron capture in hydrogen. In this paper, a method to determine the doses from thermal and fast neutrons, photons, and the B-10(n, alpha)Li-7 reaction is presented. The photon and fast neutron doses are measured with ionization chambers, in realistic phantoms, using the dual chamber technique. The thermal neutron flux is measured with gold foils using the cadmium difference technique, the thermal neutron and B-10 doses are determined by the kerma factor method. Representative results are presented for a unilateral irradiation of the head. Sources of error in the method as applied to BNCT dosimetry, and the uncertainties in the calculated doses are discussed.

Boron Neutron Capture Therapy↗
PubMed2003

Characterization of neutron beams for boron neutron capture therapy: in-air radiobiological dosimetry.

The survival curves and the RBE for the dose components generated in boron neutron capture therapy (BNCT) were determined separately in neutron beams at Japan Research Reactor No. 4. The surviving fractions of V79 Chinese hamster cells with or without 10B were obtained using an epithermal neutron beam (ENB), a mixed thermal-epithermal neutron beam (TNB-1), and a thermal (TNB-2) neutron beam; these beams were used or are planned for use in BNCT clinical trials. The cell killing effect of the neutron beam in the presence or absence of 10B was highly dependent on the neutron beam used and depended on the epithermal and fast-neutron content of the beam. The RBEs of the boron capture reaction for ENB, TNB-1 and TNB-2 were 4.07 +/- 0.22, 2.98 +/- 0.16 and 1.42 +/- 0.07, respectively. The RBEs of the high-LET dose components based on the hydrogen recoils and the nitrogen capture reaction were 2.50 +/- 0.32, 2.34 +/- 0.30 and 2.17 +/- 0.28 for ENB, TNB-1 and TNB-2, respectively. The RBEs of the neutron and photon components were 1.22 +/- 0.16, 1.23 +/- 0.16, and 1.21 +/- 0.16 for ENB, TNB-1 and TNB-2, respectively. The approach to the experimental determination of RBEs outlined in this paper allows the RBE-weighted dose calculation for each dose component of the neutron beams and contributes to an accurate inter-beam comparison of the neutron beams at the different facilities employed in ongoing and planned BNCT clinical trials.

Air↗
PubMed1998

Responses of total and quiescent cell populations in solid tumors to boron and gadolinium neutron capture reaction using neutrons with two different energy spectra.

In neutron capture therapy, whose effectiveness depends on the tumor distribution of neutron capture compound and the neutron energy distribution, controlling quiescent tumor cells with clonogenic potential is critical for therapeutic gain, as is the case in conventional radio- and chemotherapy. Tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating cells. After administration of sodium borocaptate-10B (BSH), dl-p-boronophenylalanine-10B (BPA) or gadodiamide hydrate (Omniscan), the tumors were irradiated with neutrons of different cadmium (Cd) ratio, and then isolated and incubated with cytochalasin-B (a cytokinesis blocker). The micronucleus (MN) frequency in cells without BrdU labeling (quiescent cells) was determined using immunofluorescence staining for BrdU, and that for total cells was obtained from tumors not pretreated with BrdU. Without drugs, quiescent cells showed lower MN frequencies than total cells, but neutron irradiation reduced gamma-ray sensitivity difference between the two. Relative biological effectiveness (RBE) of neutrons compared with gamma-rays was greater in quiescent cells than in total cells, and low Cd ratio neutrons tended to exhibit large RBE values. With neutron capture compounds, MN frequency for each cell population was increased, especially when high Cd ratio neutrons were used. BPA increased the MN frequency for total cells to a greater extent than BSH. However, the sensitivity of quiescent cells treated with BPA was lower than that in BSH-treated quiescent cells. This tendency was clearly observed in high Cd ratio neutrons. Omniscan only slightly increased the MN frequency in both cell populations, compared with irradiation alone, without drugs. From the viewpoint of increasing the quiescent cell sensitivity, tumors should be irradiated with high Cd ratio neutrons after BSH administration.

Animals↗
PubMedDate not supplied

Neutron-induced gamma dose from a reactor beam filter for boron neutron capture therapy.

For the boron neutron capture therapy (NCT) of deep-seated metastatic melanoma, an epithermal (up to a few keV energy) neutron beam from a reactor horizontal facility could be useful if the inherent contamination from fast neutrons and gamma rays could be minimised. Calculations for ANSTO's 10 MW research reactor HIFAR have shown that, even though a filter material such as AlF3 attenuates the fast neutron dose, the beam quality improvement is counteracted by a relative increase in the gamma dose because of the gammas arising from neutron captures in the filter material, particularly the aluminium. The aluminium gammas, most of which arise from thermal neutron capture, are hard and cannot be attenuated by lead or bismuth without comparable attenuation of the epithermal neutron flux. Addition of an absorber such as 6Li to the AlF3 filter was investigated as a means of reducing the hard gamma dose, but the improvement in beam quality was small and at considerable cost to dose intensity. Dose characteristics calculations confirmed the superiority of a tangential beam over a radial beam with better results from an unfiltered tangential beam than from an AlF3 filter in a radial beam. This study showed conclusively that assessments of filter assemblies based on the effect of individual components on either the neutron or gamma dose in isolation are inadequate. In assessing any epithermal neutron filter, thermal neutron shield, and gamma shield combination, the total effect of each on the neutron, gamma, and boron-10 dose must be considered.

Boron↗
PubMed2002

Feasibility of assessing the carcinogenicity of neutrons among neutron therapy patients.

Nuclear workers, oil well loggers, astronauts, air flight crews, and frequent fliers can be exposed to low doses of neutrons, but the long-term human health consequences of neutron exposure are unknown. While few of these exposed populations are suitable for studying the effects of neutron exposure, patients treated with neutron-beam therapy might be a source of information. To assess the feasibility of conducting a multi-center international study of the late effects of neutron therapy, we surveyed 23 cancer centers that had used neutron beam therapy. For the 17 responding institutions, only 25% of the patients treated with neutrons (2,855 of 11,191) were alive more than 2 years after treatment. In a two-center U.S. pilot study of 484 neutron-treated cancer patients, we assessed the feasibility of obtaining radiotherapy records, cancer incidence and other follow-up data, and of estimating patient organ doses. Patients were treated with 42 MeV neutrons between 1972 and 1989. Applying a clinical equivalence factor of 3.2 for neutrons, total average organ doses outside the treatment beam ranged from 0.14 to 0.29 Gy for thyroid, 0.40 to 2.50 Gy for breast, 0.63 to 2.35 Gy for kidney, and 1.12 to 1.76 Gy for active bone marrow depending upon the primary cancer treatment site. We successfully traced 97% of the patients, but we found that patient survival was poor and that chemotherapy was not confirmable in a quarter of the patients. Based on our findings from the international survey and the feasibility study, we conclude that a large investigation could detect a fivefold or higher leukemia risk, but would be inadequate to evaluate the risk of solid cancers with long latent periods and therefore would likely not be informative with respect to neutron-related cancer risk in humans.

Carcinogenicity Tests↗
PubMed1994

Boron neutron capture therapy: a mechanism for achieving a concomitant tumor boost in fast neutron radiotherapy.

PURPOSE: For many years neutron radiation has been used to treat malignant disease both as fast neutron radiotherapy and as thermal neutron induced boron neutron capture therapy (BNCT). To date, these two approaches have been used independently of one another due to the large difference in neutron energies each employs. In this paper we discuss the potential application of BNCT to enhance the therapeutic effectiveness of a fast neutron radiotherapy beam. METHODS AND MATERIALS: Measurements are presented for the thermal neutron component that is spontaneously developed as the University of Washington fast neutron radiotherapy beam penetrates a water phantom. The biological effect of this thermalized component on cells "tagged" with boron-10 (10B) is modeled mathematically and the expected change in cell survival calculated. The model is then extended to estimate the effect this enhanced cell killing would have for increased tumor control. RESULTS: The basic predictions of the model on changes in cell survival are verified with in vitro measurements using the V-79 cell line. An additional factor of 10-100 in tumor cell killing appears achievable with currently available 10B carriers using our present neutron beam. A Poisson model is then used to estimate the change in tumor control this enhanced cell killing would produce in various clinical situations and the effect is sufficiently large so as to be clinically relevant. It is also demonstrated that the magnitude of the thermalized component can be increased by a factor of 2-3 with relatively simple changes in the beam generating conditions. CONCLUSION: BNCT may provide a means of enhancing the therapeutic effectiveness of fast neutron radiotherapy in a wide variety of clinical situations and is an area of research that should be aggressively pursued.

Boron Neutron Capture Therapy↗
PubMed1994

Dose enhancement in fast neutron tumour therapy due to neutron captures in 10B.

High energy neutrons, applied in fast neutron tumour therapy, lose energy when passing through tissue and are at the end of their trajectories captured in nitrogen, hydrogen or other normally occurring elements. If the tissue contains 10B, which has a very high cross section for capture of thermal neutrons, then disintegration products of this process, helium and lithium ions, give a dose enhancement which, if the boron is targeted to tumour cells, may be beneficial. The dose enhancement was in the present study calculated as a function of the 10B concentration in the cells and as a function of different thermal neutron fluencies. If the tumour cells contained 10 or 100 microns 10B/g the average dose enhancement was about 20 or 200 mGy respectively. This was obtained with the thermal neutron fluency 2.0 x 10(10) n/cm2. The relative biological effectiveness of the neutron capture process is unknown but assuming the factor 2, these doses correspond to 0.04 or 0.4 CGE (cobolt-60 gray equivalent) respectively, which could directly be compared to the 2-3 Gy of low-LET radiation that is daily applied in conventional radiotherapy. However, if thermal or epithermal neutron fields are directly applied to the patients a hundred times higher thermal neutron fluency can be used. This gives, in the cases with 10 or 100 micrograms 10B/g, about a hundred times higher average doses so that 2-20 Gy, corresponding to about 4-40 CGE, can be given to the patients. Thus, a successful targeting with high amounts of 10B in the tumour cells gives a significant dose enhancement when applied in fast neutron therapy but it is then more reasonable to treat the patient directly with thermal or epithermal neutrons since the average dose enhancement in the latter case is about a hundred times higher and curable doses might be obtained by the tumour specific capture processes alone.

Boron Neutron Capture Therapy↗
PubMed2002

Alterations in water and electrolyte absorption in the rat colon following neutron irradiation: influence of neutron component and irradiation dose.

PURPOSE: To study the absorptive function of rat colon following whole-body exposure to neutron irradiation, either to the same total dose with varying proportion of neutrons or to the same neutron proportion with an increasing irradiation dose. MATERIALS AND METHODS: Different proportions of neutron irradiation were produced from the reactor SILENE using a fissile solution of uranium nitrate (8, 47 and 87% neutron). Water and electrolyte fluxes were measured in the rat in vivo under anaesthesia by insertion into the descending colon of an agarose gel cylinder simulating the faeces. Functional studies were completed by histological analyses. In the first set of experiments, rats received 3.8 Gy with various neutron percentages and were studied from 1 to 14 days after exposure. In the second set of experiments, rats were exposed to increasing doses of irradiation (1-4Gy) with a high neutron percentage (87%n) and were studied at 4 days after exposure. RESULTS AND CONCLUSIONS: The absorptive capacity of rat colon was diminished by irradiation at 3-5 days, with a nadir at 4 days. The results demonstrate that an increase in the neutron proportion is associated with an amplification of the effects. Furthermore, a delay in the re-establishment of normal absorption was observed with the high neutron proportion (87%n). A dose-dependent reduction of water absorption by rat colon was also observed following neutron irradiation (87%n), with a 50% reduction at 3 Gy. Comparison of this dose-effect curve with the curve obtained following gamma (60)Co-irradiation indicates an RBE of 2.2 for absorptive colonic function in rat calculated at 4 days after exposure.

Absorption↗
PubMed2005

Differential absorbed dose distributions in lineal energy for neutrons and gamma rays at the mono-energetic neutron calibration facility.

Absorbed dose distributions in lineal energy for neutrons and gamma rays of mono-energetic neutron sources from 140 keV to 15 MeV were measured in the Fast Neutron Laboratory at Tohoku University. By using both a tissue-equivalent plastic walled counter and a graphite-walled low-pressure proportional counter, absorbed dose distributions in lineal energy for neutrons were obtained separately from those for gamma rays. This method needs no knowledge of energy spectra and dose distributions for gamma rays. The gamma-ray contribution in this neutron calibration field >1 MeV neutron was <3%, while for <550 keV it was >40%. The measured neutron absolute absorbed doses per unit neutron fluence agreed with the LA150 evaluated kerma factors. By using this method, absorbed dose distributions in lineal energy for neutrons and gamma rays in an unknown neutron field can be obtained separately.

Absorption↗
PubMedDate not supplied

Boron neutron capture therapy for the treatment of cerebral gliomas. I. Theoretical evaluation of the efficacy of various neutron beams.

The technique of boron neutron capture therapy in the treatment of cerebral gliomas depends upon the selective loading of the tumor with a 10B-enriched compound and subsequent irradiation of the brain with low-energy neutrons. The charged particles produced in the 10B (n,alpha) 7Li reaction have ranges in tissue of less than 10 mum so that the dose distribution closely follows the 10B distribution even to the cellular level. The effectiveness of this therapy procedure is dependent not only on the 10B compound but on the spectral characteristics of the neutron source as well. Hence, an optimization of these characteristics will increase the chances of therapeutic success. Transport calculations using a neutral particle transport code have been made to determine the dose-depth distributions within a simple head phantom for five different incident neutron beams. Comparison of these beams to determine their relative therapeutic efficacy was made by the use of a maximum useable depth criterion. In particular, with presently available compounds, the MIT reactor (MITR) therapy beam (a) is not inferior to a pure thermal neutron beam, (b) would be marginally improved if its gamma-ray contamination were eliminated, (c) is superior to a partially 10B-filtered MITR beam, and (d) produces a maximum useable depth which is strongly dependent upon the tumor-to-blood ratio of 10B concentrations and weakly dependent upon the absolute 10B concentration in tumor. A pure epithermal neutron beam with a mean energy of 37 eV is shown to have close to the optimal characteristics for boron neutron capture therapy. Futhermore, these optimal characteristics can be approximated by a judiciously D2O moderated and 10B-filtered 252Cf neutron source. This tailored 252Cf source would have at least a 1.5 cm greater maximum useable depth than the MITR therapy beam for realistic 10B concentrations. However, at least one gram of 252Cf would be needed to make this a practical therapy source. If the moderated 252Cf source is not 10B filtered, the resultant neutron beam has characteristics similar to those of the MITR beam with no gamma-ray contamination. For usch a beam, 100 mg of 252Cf would produce a flux of 2.4 X 10(8) neutrons/(cm2 sec), which is an intensity suitable for therapy applications.

Boron↗
PubMed2001

Experimental verification of improved depth-dose distribution using hyper-thermal neutron incidence in neutron capture therapy.

We have proposed the utilization of 'hyper-thermal neutrons' for neutron capture therapy (NCT) from the viewpoint of the improvement in the dose distribution in a human body. In order to verify the improved depth-dose distribution due to hyper-thermal neutron incidence, two experiments were carried out using a test-type hyper-thermal neutron generator at a thermal neutron irradiation field in Kyoto University Reactor (KUR), which is actually utilized for NCT clinical irradiation. From the free-in-air experiment for the spectrum-shift characteristics, it was confirmed that the hyper-thermal neutrons of approximately 860 K at maximum could be obtained by the generator. From the phantom experiment, the improvement effect and the controllability for the depth-dose distribution were confirmed. For example, it was found that the relative neutron depth-dose distribution was about 1 cm improved with the 860 K hyper-thermal neutron incidence, compared to the normal thermal neutron incidence.

Hot Temperature↗
PubMed1994

Thick beryllium target as an epithermal neutron source for neutron capture therapy.

Accelerator-based intense epithermal neutron sources for Neutron Capture Therapy (NCT) have been considered as an alternative to nuclear reactors. Lithium (Li) has generally received the widest attention for this application, since the threshold energy is low and neutron yield is high. Because of the poor thermal and chemical properties of Li and the need for heat removal in the target, the design of Li targets has been quite difficult. Beryllium (Be) has been thought of as an alternative target because of its good thermal and chemical properties and reasonable neutron yield. However, in order to have a neutron yield comparable to that of a thick Li target bombarded with 2.5 MeV protons, the proton energy required for a thick Be target must be approaching 4 MeV. Consequently, the neutrons emitted are more energetic. In addition, a significant amount of high-energy gamma rays, which is undesirable, will occur when Be is bombarded with low-energy protons. Regardless of the more energetic neutrons and additional gamma rays, in this paper it is shown that it is possible to develop a high-quality and high-intensity epithermal neutron beam based on a thick Be target for NCT treatment. For a fixed proton current, the optimal Be-target-based beam (with 4-MeV protons) can produce a neutron beam, with both quality and intensity slightly better than those produced by the optimal Li-target-based beam (with 2.5-MeV protons). The single-session NCT treatment time for the optimal Be-target-based beam is estimated to be 88 min for a proton current of 50 mA.(ABSTRACT TRUNCATED AT 250 WORDS)

Beryllium↗
PubMed1982

Triple chamber technique for thermal neutron dose measurements in fast neutron beams.

Collimated fast neutron beams used in radiotherapy are always contaminated with photons and thermal neutrons. From foil activation measurements the relative dose contribution of thermal neutrons to the absorbed neutron dose in different depths in a tissue equivalent phantom was determined. The sensitivities of a TE-Chamber, a GM-counter with a 6Li-shield and an unshielded GM-counter to fast neutrons, thermal neutrons and photons are presented. The triple chamber technique using these three devices is compared to foil activation technique with respect to the determination of relative thermal neutron depth dose curves. Finally the triple chamber technique is applied for the determination of depth dose curves of fast neutrons, thermal neutrons and photons in a solid TE-phantom.

Fast Neutrons↗