A phantom experiment for the evaluation of whole body exposure during BNCT using cyclotron-based epithermal neutron source (C-BENS)

At Kyoto University Research Reactor Institute (KURRI), cyclotron-based epithermal neutron source was installed in December 2008, and the supplementary construction works have been performed. As of December 2010, the various irradiation characteristics important for BNCT were mostly evaluated. The whole body exposure during BNCT medical irradiation is one of the important characteristics.In this article, measurements of absorbed dose for thermal and fast neutrons and gamma-ray at ten positions corresponding to important organs are reported.     

Evaluation of thermal neutron irradiation field using a cyclotron-based neutron source for alpha autoradiography

It is important to measure the microdistribution of ¹⁰B in a cell to predict the cell-killing effect of new boron compounds in the field of boron neutron capture therapy. Alpha autoradiography has generally been used to detect the microdistribution of ¹⁰B in a cell. Although it has been performed using a reactor-based neutron source, the realization of an accelerator-based thermal neutron irradiation field is anticipated because of its easy installation at any location and stable operation. Therefore, we propose a method using a cyclotron-based epithermal neutron source in combination with a water phantom to produce a thermal neutron irradiation field for alpha autoradiography. This system can supply a uniform thermal neutron field with an intensity of 1.7×10⁹ (cm⁻² s⁻¹) and an area of 40 mm in diameter. In this paper, we give an overview of our proposed system and describe a demonstration test using a mouse liver sample injected with 500 mg/kg of boronophenyl-alanine.     

Experimental verification of beam characteristics for cyclotron-based epithermal neutron source (C-BENS)

A cyclotron-based epithermal neutron source has been developed for boron neutron capture therapy. This system consists of a cyclotron accelerator producing 1.1-mA proton beams with an energy of 30 MeV, a beam transport system coupled with a beryllium neutron production target, and a beam-shaping assembly (BSA) with a neutron collimator. In our previous work, the BSA was optimized to obtain sufficient epithermal neutron fluxes of using a Monte Carlo simulation code. In order to validate the simulation results, irradiation tests using multi-foil activation at the surface of a gamma-ray shield located behind the collimator and water phantom experiments using a collimated epithermal neutron beam were performed. It was confirmed experimentally that the intensity of the epithermal neutrons was 1.2×10⁹ cm⁻² s⁻¹.     

Monte-Carlo calculations for the development of a BNCT neutron source at the Kyiv Research Reactor.

The results presented in this paper display our continuing steps toward development of a neutron source with parameters required by boron neutron capture therapy (BNCT) at the Kyiv Research Reactor (KRR). The purpose of this work was: 1. calculation of the neutron flux which can be achieved at the greatest possible approach of a patient to the reactor core; 2. analysis of the influence of a nickel collimator and a nickel-60 filter on the characteristics of the neutron beam; 3. creation and validation of the MCNP calculational pattern for an actual core fuel load in the KRR. Results of calculations were carried out by means of the MCNP4C code included: 1. An epithermal neutron flux of 3x10(9)-5x10(9)neutron/cm(2)s with an epithermal-to-fast flux ratio of 80-230 could be obtained at the KRR, using a natural nickel layer on the interior borated polyethylene collimator wall and a (60)Ni filter. 2. Use of the (60)Ni filter may be useful to increase the ratio epithermal-to-fast flux without a substantial decrease in the magnitude of the epithermal neutron flux. 3. The MCNP model proposed in this paper could also be useful for reactor safety calculations.     

A feasibility study of the Tehran research reactor as a neutron source for BNCT

Investigation on the use of the Tehran Research Reactor (TRR) as a neutron source for Boron Neutron Capture Therapy (BNCT) has been performed by calculating and measuring energy spectrum and the spatial distribution of neutrons in all external irradiation facilities, including six beam tubes, thermal column, and the medical room. Activation methods with multiple foils and a copper wire have been used for the mentioned measurements. The results show that (1) the small diameter and long length beam tubes cannot provide sufficient neutron flux for BNCT; (2) in order to use the medical room, the TRR core should be placed in the open pool position, in this situation the distance between the core and patient position is about 400 cm, so neutron flux cannot be sufficient for BNCT; and (3) the best facility which can be adapted for BNCT application is the thermal column, if all graphite blocks can be removed. The epithermal and fast neutron flux at the beginning of this empty column are 4.12×10⁹ and 1.21×10⁹ n/cm²/s, respectively, which can provide an appropriate neutron beam for BNCT by designing and constructing a proper Beam Shaping Assembly (BSA) structure.     

Renovation of epithermal neutron beam for BNCT at THOR.

Heading for possible use for clinical trial, THOR (Tsing Hua Open-pool Reactor) at Taiwan was shutdown for renovation of a new epithermal neutron beam in January 2003. In November 2003, concrete cutting was finished for closer distance from core and larger treatment room. This article presents the design base that the construction of the new beam is based on. The filter/moderator design along the beam is Cd(0.1cm)+Al(10 cm)+FLUENTAL (16 cm)+Al(10 cm)+FLUENTAL(24 cm)+Void(18 cm)+Cd(0.1cm)+Bi(10 cm) with 6 cm Pb as reflector. Following the filter/moderator is an 88 cm long, 6 cm thick Bi-lined collimator with Li(2)CO(3)-PE at the end. The collimator is surrounded by Li(2)CO(3)-PE and Pb. The calculated beam parameters under 2 MW at the beam exit is phi(epi) = 3.4 x 10(9) n/cm(2)/s, Df/phi(epi) = 2.8 x 10(-11) cGy cm(2)/n, Dgamma/phi(epi) = 1.3 x 10(-11) cGy cm(2)/n, and J+/phi = 0.8. For a phantom placed 10 cm from beam exit, MCNP calculation shows that the advantage depth is 8.9 cm, and advantage ratio is 5.6 if boron concentration in tumor and normal tissue are assumed to be 65 and 18 ppm. The maximum dose rate for normal tissue is 50 cGy/min. The maximum therapeutic ratio is 6. The construction of the beam is scheduled to be finished by the end of April 2004.     

Characteristics of the new THOR epithermal neutron beam for BNCT.

A characterization of the new Tsing Hua open-pool reactor (THOR) epithermal neutron beam designed for boron neutron capture therapy (BNCT) has been performed. The facility is currently under construction and expected in completion in March 2004. The designed epithermal neutron flux for 1 MW power is 1.7x10(9)n cm(-2)s(-1) in air at the beam exit, accompanied by photon and fast neutron absorbed dose rates of 0.21 and 0.47 mGys(-1), respectively. With (10)B concentrations in normal tissue and tumor of 11.4 and 40 ppm, the calculated advantage depth dose rate to the modified Snyder head phantom is 0.53RBE-Gymin(-1) at the advantage depth of 85 mm, giving an advantage ratio of 4.8. The dose patterns determined by the NCTPlan treatment planning system using the new THOR beam for a patient treated in the Harvard-MIT clinical trial were compared with results of the MITR-II M67 beam. The present study confirms the suitability of the new THOR beam for possible BNCT clinical trials.     

Development of equipments for determination of BNCT source spectral parameters.

The knowledge of neutron and gamma ray energy spectra can strongly influence the BNCT information about delivered dose to target volume as well as to the surface healthy tissue region. This region is very often decisive to stay within the recommended healthy tissue limit. Modification of neutron Bonner spectrometer to one block i.e. Bonner spectrometer monoblock (BSM) and gamma ray Si semiconductor spectrometer are being developed and verified in real conditions of LVR-15 reactor beam. Test measurements were also carried out in conditions of known standard spectra. The accepted procedure and the first results documenting the sensitivity BSM to different spectra are presented.     

Lithium neutron producing target for BINP accelerator-based neutron source.

Pilot innovative accelerator-based neutron source for neutron capture therapy is under construction now at the Budker Institute of Nuclear Physics, Novosibirsk, Russia. One of the main elements of the facility is lithium target, that produces neutrons via threshold (7)Li(p,n)(7)Be reaction at 25 kW proton beam with energies 1.915 or 2.5 MeV. In the present report, the results of experiments on neutron producing target prototype are presented, the results of calculations of hydraulic resistance for heat carrier flow and lithium layer temperature are shown. Calculation showed that the lithium target could run up to 10 mA proton beam before melting. Choice of target variant is substantiated. Program of immediate necessary experiments is described. Target design for neutron source constructed at BINP is presented. Manufacturing the neutron producing target up to the end of 2004 and obtaining a neutron beam on BINP accelerator-based neutron source are planned during 2005.     

Resumption of JRR-4 and characteristics of neutron beam for BNCT

The clinical trials of Boron Neutron Capture Therapy (BNCT) have been conducted using Japan Research Reactor No. 4 (JRR-4) at Japan Atomic Energy Agency (JAEA). On December 28th, 2007, a crack of a graphite reflector in the reactor core was found on the weld of the aluminum cladding. For this reason, specifications of graphite reflectors were renewed; dimensions of the graphite were reduced and gaps of water were increased. All existing graphite reflectors of JRR-4 were replaced by new graphite reflectors. In February 2010 the resumption of JRR-4 was carried out with new graphite reflectors. We measured the characteristics of neutron beam at the JRR-4 Neutron Beam Facility. A cylindrical water phantom of 18.6 cm diameter and 24 cm depth was set in front of the beam port with 1 cm gap. TLDs and gold wires were inserted within the phantom when the phantom was irradiated. The results of the measured thermal neutron flux and the gamma dose in water were compared with that of MCNP calculation. The neutron energy spectrum of the calculation model with new reflector had little variation compared to that with old reflector, but intensities of the neutron flux and gamma dose with new reflector were rather smaller than those with old reflector. The calculated results showed the same tendency as that of the experimental results. Therefore, the clinical trials of BNCT in JRR-4 could be restarted.     

Dosimetry of the boron neutron capture reaction for BNCT and BNCEFNT

Strahlentherapie und Onkologie - The use of paired proportional counters, constructed from A-150 tissue equivalent plastic (TEP) and A-150 TEP loaded with an appropriate amount of10B (50 to 200...     

Quality assurance procedures for the neutron beam monitors at the FiR 1 BNCT facility.

In order to assure the stability of the beam, the reliability of the beam monitoring system and the quality of the patient dose delivered, several procedures are followed at the FiR 1 epithermal beam in Finland. Routine procedures include in-phantom activation measurements before each patient treatment and a long-term follow-up of the results. The sensitivity of the beam monitors to external objects in the beam and to variations in the control rod positions in the reactor has been checked and found insignificant. The linearity of the beam monitor channels has been checked with activation measurements. It was found that due to saturation effects a correction of 11% has to be applied when extrapolating results from experiments at low power to full power using the reference monitor channel. The correction is even larger for other channels with higher count rates.     

Optimization of an accelerator-based epithermal neutron source for neutron capture therapy.

A modeling investigation was performed to choose moderator material and size for creating optimal epithermal neutron beams for BNCT based on a proton accelerator and the (7)Li(p,n)(7)Be reaction as a neutrons source. An optimal configuration is suggested for the beam shaping assembly made from polytetrafluoroethylene and magnesium fluorine to be placed on high current IPPE proton accelerator KG-2.5. Results of calculation were experimentally tested and are in good agreement with measurements.     

Measurement of free beam neutron spectra at eight BNCT facilities worldwide.

Eight epithermal neutron beams, constructed for clinical or preclinical studies of NCT, have been dosimetrically characterized by in-air measurements with a set of activation foils for the determination of the neutron energy spectra in free beam. Measurements have been made on the already closed epithermal BNCT facility at the BMRR of the Brookhaven National Laboratory, on the HFR at JRC in Petten, The Netherlands, on the epithermal mode beam at KURRI, Japan, on the fission converter beam at MIT, USA, on the epithermal beam of the RA-6 facility in Bariloche, Argentina, on the epithermal beam at WSU, USA, on the mixed mode beam at JRR-4 at JAERI, Japan, as well as on the epithermal beam at FiR 1 at VTT, Espoo, Finland.     

Intercalibration of physical neutron dosimetry for the RA-3 and MURR thermal neutron sources for BNCT small-animal research

New thermal neutron irradiation facilities to perform cell and small-animal irradiations for Boron Neutron Capture Therapy research have been installed at the Missouri University Research Reactor and at the RA-3 research reactor facility in Buenos Aires, Argentina. Recognizing the importance of accurate and reproducible physical beam dosimetry as an essential tool for combination and intercomparisons of preclinical and clinical results from the different facilities, we have conducted an experimental intercalibration of the neutronic performance of the RA-3 and MURR thermal neutron sources.     

A shielding design for an accelerator-based neutron source for boron neutron capture therapy.

Research in boron neutron capture therapy (BNCT) at The Ohio State University Nuclear Engineering Department has been primarily focused on delivering a high quality neutron field for use in BNCT using an accelerator-based neutron source (ABNS). An ABNS for BNCT is composed of a proton accelerator, a high-energy beam transport system, a (7)Li target, a target heat removal system (HRS), a moderator assembly, and a treatment room. The intent of this paper is to demonstrate the advantages of a shielded moderator assembly design, in terms of material requirements necessary to adequately protect radiation personnel located outside a treatment room for BNCT, over an unshielded moderator assembly design.     

GE PETtrace cyclotron as a neutron source for boron neutron capture therapy.

This paper discusses the use of a General Electric PETtrace cyclotron as a neutron source for boron neutron capture therapy. In particular, the standard PETtrace (18)O target is considered. The resulting dose from the neutrons emitted from the target is evaluated using the Monte Carlo radiation transport code MCNP at different depths in a brain phantom. MCNP-simulated results are presented at 1, 2, 3, 4, 5, 6, 7, and 8 cm depth inside this brain phantom. Results showed that using a PETtrace cyclotron in the current configuration allows treating tumors at a depth of up to 4 cm with reasonable treatment times. Further increase of a beam current should significantly improve the treatment time and allow treating tumors at greater depths.     

Clinical results of boron neutron capture therapy (BNCT) for glioblastoma

The purpose of this study was to evaluate the clinical outcome of BSH-based intra-operative BNCT (IO-BNCT) and BSH and BPA-based non-operative BNCT (NO-BNCT). We have treated 23 glioblastoma patients with BNCT without any additional chemotherapy since 1998. The median survival time (MST) of BNCT was 19.5 months, and 2-year, 3-year and 5-year survival rates were 26.1%, 17.4% and 5.8%, respectively. This clinical result of BNCT in patients with GBM is superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment.