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PubMed2000

[Radiotherapy of high grade glioma: use of fast neutrons, therapy and enhancement by neutron capture].

Among high linear energy transfer (LET) irradiations techniques, those using fast neutrons are able to eradicate glioblastoma cells. At least a 13 grays (Gy) irradiation dose has to be used, but high morbidity is observed in case of over 11 Gy irradiation. So, no therapeutic windows have been found despite the fact that more than 900 patients were included in clinical trials. Boron neutron capture therapy (BNCT) uses alpha emitting nuclear reactions, produced within tumoral cells by boron neutron captures. (10)B is specifically loaded inside tumoral cells via a boronated molecule, and the tissues are then irradiated with thermal or epithermal neutrons. Although this type of irradiation is yet considered as a regular method in Japan, USA and Europe have started clinical trials, currently in progress, in order to define the BNCT place in the post-operative care of high grade glioma. Non-removable tumors may benefit from boron neutron capture enhancement of fast neutron irradiation, i.e. the combination of these two methods. Preliminary studies show that a "biological" dose enhancement of 20 % could be obtained within the tumor when a concentration of 100 microg/g of (10)B is targeted into it. These concentrations are achievable by intra-arterial administration of (10)boronophenylalanine (BPA) or borosulfhydryl (BSH). Recently, some publications have also demonstrated that the thermal neutron flux yielded within the irradiated tissues could be increased. Clinical trials, using this technique, are planned in USA and Europe.

Boron Neutron Capture Therapy↗
PubMed1990

Neutron radiotherapy in adenoidcystic carcinoma: preliminary experience at the Münster neutron facility.

In adenoidcystic carcinoma macroscopic residual disease after surgery, inoperable and recurrent tumors are characterized by relapse rates up to 70% if treated according to conventional treatment strategies including photon radiotherapy. By neutron therapy a tumor control rate of 70% has been reported. At the d,T-generator (14 MeV) in Münster nine patients with adenoidcystic carcinoma of the salivary glands in locally advanced stage have been treated since 1/86. A combined modality schedule (30 Gy photon/5 to 10 Gy neutrons) used in the beginning has been replaced by a definitive neutron therapy (15 Gy) with single fractions of 1.0 to 1.3 Gy in five to six weeks. Treatment planning included CT/MRI as well as computer assisted dose calculations based on a specific software for neutron therapy. The volume reduction by neutron radiotherapy was 82% for advanced disease. Continuous remission was achieved in seven of nine patients in a short follow-up period of medium 15 months (from six to 28 months). The two recurrences occurred at the field edge. Based on this preliminary experience and on a survey of the literature the main issues for neutron therapy in salivary glands tumors in particular adenoidcystic carcinomas are discussed: histology, stage, tumor size, location, surgery, treatment planning and delivery, dose, and side effects. A long term evaluation of neutron therapy within a controlled clinical multicenter trial is proposed.

Adult↗
PubMed1979

[Cytogenetic effects induced by neutrons in human peripheral blood lymphocytes in vitro. I. Dose-effect relationship for different types of chromosome aberrations when exposed to neutrons with different energies].

Human lymphocytes were irradiated in vitro during G0 stage by graded doses of thermal neutrons and of neutrons with mean energy of 0.04; 0.09; 0.35; 0.85 and 14.7 MeV as well as by 60Co gamma-rays. The data were fitted to the linear and linear-quadratic relations. The neutrons of low and intermediate energies showed the linear dependence on the dose, 14.7 MeV neutrons and gamma-rays--a linear-quadratic one, whereas the data obtained with 0.85 MeV neutrons fitted well the both models. Terminal and interstitial deletions produced by both gamma-rays and neutrons showed different dependencies upon the dose. Some qualitative pecularities of aberration spectra were found in the experiments with neutrons as compared with the data on gamma-irradiation: the ratio of exchanges to fragments was greater, and aberrations of chromatid type were produced. The specially designed experiments and calculations showed that the last effect was not connected with induced radioactivity.

Cells, Cultured↗
PubMed1996

Dose monitoring for boron neutron capture therapy using a reactor-based epithermal neutron beam.

The aims of this study were (i) to determine the variation with time of the relevant beam parameters of a clinical reactor-based epithermal neutron beam for boron neutron capture therapy (BNCT) and (ii) to test a monitoring system for its applicability to monitor the dose delivered to the dose specification point in a patient treated with BNCT. For this purpose two fission chambers covered with Cd and two GM counters were positioned in the beam-shaping collimator assembly of the epithermal neutron beam. The monitor count rates were compared with in-phanton reference measurements of the thermal neutron fluence rate, the gamma-ray dose rate and the fast neutron dose rate, at a constant reactor power, over a period of 2 years. Differences in beam output, defined as the thermal neutron fluence rate at 2 cm depth in a phantom, of up to 15% were observed between various reactor cycles. A decrease in beam output of about 5% was observed in each reactor cycle. An unacceptable decrease of 50% in beam output due to malfunctioning of the beam filter assembly was detected. For safe and accurate treatment of patients, on-line monitoring of the beam is essential. Using the calibrated monitor system, the standard uncertainty in the total dose at depth due to variations with time of the beam output parameters has been reduced to a clinically acceptable value of 1% (one standard deviation).

Boron Neutron Capture Therapy↗
PubMed2005

Neutron multiplicity in the fission of 238U and 235U with neutrons up to 200 MeV.

Prompt-fission-neutron multiplicities were measured for 238U(n,f) and 235U(n,f) from 0.4 to 200 MeV. The data are of great importance in connection with accelerator-coupled nuclear reactor systems incinerating actinides. We report that fission induced by 200 MeV neutrons produces approximately 10 more prompt neutrons than fission induced by reactor neutrons. Most neutrons are evaporated from the fission fragments and the prefission compound nucleus, as the preequilibrium emission of energetic neutrons accounts for a maximum of 15% of the prompt neutrons at 200 MeV.

Journal Article↗
PubMed1992

Use of spherical targets to minimize effects of neutron scattering by hydrogen in neutron capture prompt gamma-ray activation analysis.

For hydrogenous targets that are thinner than they are wide, element sensitivities (counts.s-1.mg-1) for determining concentrations of elements by neutron capture prompt gamma-ray activation analysis (PGAA) are enhanced relative to sensitivities obtained from measurements on nonhydrogenous materials. These enhancements are caused mainly by elastic neutron scattering by H, which changes the average neutron fluence rate within the matrix. The magnitude of the effect depends on the macroscopic scattering and absorption cross sections and on the size, shape, and orientation of the target with respect to the neutron beam. Sensitivities increase linearly with H density for thin targets of constant size and shape and also vary with target shape. Theoretical work was shown that element sensitivities for hydrogenous targets in the form of spheres are least affected by neutron scattering. Methods were devised for creating solid spheres and for containing liquids in spherical shapes. Element sensitivities were determined for spheres and disks of several hydrogenous materials. For H, B, Cl, K, Br, and Cd, sensitivities for spheres were found to be less affected by neutron scattering. Exceptions were Sm and Gd sensitivities measured in liquids contained in quartz globes.

Chemistry Techniques, Analytical↗
PubMed1978

Neutron spectra from deuteron and proton bombardment of thick lithium targets: potential for neutron therapy.

Neutron energy spectra and yields produced by the bombardment of thick lithium targets by deuterons and protons have been measured using the time-of-flight method. Measurements were made at angles up to 45 degrees for deuteron energies of 8, 12 and 15 MeV and a proton energy of 15 MeV. The average neutron energy of the (d, n) reactions is shown to vary approximately as 0.44Ed. The (p, n) reaction has En = 4.7 MeV. The tissue penetration of neutron therapy beams is dependent on their average neutron energy and thus the low average neutron energy for these reactions appears to preclude their use for practical neutron therapy at these incident particle energies.

Deuterium↗
PubMed1981

The basis of a suggested instrumental approach to the surveying of neutron fields and the measurement of personal dose from neutrons.

The basis of a two-component neutron monitoring system that could be applied to both survey instruments and personal dosemeters is considered. Neutrons with energies below 10 keV are detected by a thermal neutron detector which, in the survey instrument, is located inside a small moderating sphere, whereas in the personal dosemeter it is positioned behind a thermal neutron shield located on an individual's body. Neutrons above 10 keV are detected by counting pulses produced by protons ejected from a thin hydrogenous foil. By judicious choice of the characteristics of the detection elements, it is possible to ensure that the sum of the sensitivities of the elements of both survey instrument and personal dosemeter vary with neutron energy in a way close to that required for radiological protection purposes throughout the range thermal-10 MeV. The realisation of the elements sensitive below 10 keV presents few fundamental problems and appropriate devices have been reported in the literature. Those sensitive above 10 keV have proved to be more difficult to realise in practice.

Fast Neutrons↗
PubMed2000

Study of moderator thickness for an accelerator-based neutron irradiation facility for boron neutron capture therapy using the 7Li(p,n) reaction near threshold.

Accelerator neutron sources for epithermal neutron capture therapy utilizing the 7Li(p,n) nuclear reaction will require a moderator even in the threshold range of 1.89 to 1.95 MeV. The corresponding neutron energies allow for a thinner reflector and moderator, with less reduction of the epithermal flux. To estimate the useful neutron flux within the epithermal range (4 eV-40 keV), the optimal thickness of a heavy water moderator was determined using the two-dimensional neutron transport S(N) code DORT. Optimized results are compared with the epithermal fluxes reported for the higher proton energy range, and are found to be inferior. Thus, this study supports the 2.5-3.0 MeV proton energy range for accelerator boron neutron capture therapy.

Boron Neutron Capture Therapy↗
PubMed2001

A comparison of neutron beams for BNCT based on in-phantom neutron field assessment parameters.

In this paper our in-phantom neutron field assessment parameters, T and DTumor, were used to evaluate several neutron sources for use in BNCT. Specifically, neutron fields from The Ohio State University (OSU) Accelerator-Based Neutron Source (ABNS) design, two alternative ABNS designs from the literature (the Al/AIF3-Al2O3 ABNS and the 7LiF-AI2O3 ABNS), a fission-convertor plate concept based on the 500-kW OSU Research Reactor (OSURR), and the Brookhaven Medical Research Reactor (BMRR) facility were evaluated. In order to facilitate a comparison of the various neutron fields, values of T and DTumor were calculated in a 14 cm x 14 cm x 14 cm lucite cube phantom located in the treatment port of each neutron source. All of the other relevant factors, such as phantom materials, kerma factors, and treatment parameters, were kept the same. The treatment times for the OSURR, the 7LiF-Al2O3 ABNS operating at a beam current of 10 mA, and the BMRR were calculated to be comparable and acceptable, with a treatment time per fraction of approximately 25 min for a four fraction treatment scheme. The treatment time per fraction for the OSU ABNS and the Al/AlF3-Al2O3 ABNS can be reduced to below 30 min per fraction for four fractions, if the proton beam current is made greater than approximately 20 mA. DTumor was calculated along the bean centerline for tumor depths in the phantom ranging from 0 to 14 cm. For tumor depths ranging from 0 to approximately 1.5 cm, the value of DTumor for the OSURR is largest, while for tumor depths ranging from 1.5 to approximately 14 cm, the value of DTumor for the OSU-ABNS is the largest.

Boron Neutron Capture Therapy↗
PubMed2002

The medical-irradiation characteristics for neutron capture therapy at the Heavy Water Neutron Irradiation Facility of Kyoto University Research Reactor.

At the Heavy Water Neutron Irradiation Facility of the Kyoto University Research Reactor, the mix irradiation of thermal and epi-thermal neutrons, and the solo irradiation of epi-thermal neutrons are available additionally to the thermal neutron irradiation, and then the neutron capture therapy (NCT) at this facility became more flexible, after the update in 1996. The estimation of the depth dose distributions in NCT clinical irradiation, were performed for the standard irradiation modes of thermal, mixed and epi-thermal neutrons, from the both sides of experiment and calculation. On the assumption that the 10B concentration in tumor part was 40 ppm and the ratio of tumor to normal tissue was 3.5, the advantage depth were estimated to 5.4, 6.0, and 8.0, for the respective standard irradiation modes. It was confirmed that the various irradiation conditions can be selected according to the target-volume conditions, such as size, depth, etc. Besides, in the viewpoint of the radiation shielding for patient, it was confirmed that the whole-body exposure is effectively reduced by the new clinical collimators, compared with the old one.

Antineoplastic Agents↗
PubMed1995

Determination of dose components in phantoms irradiated with an epithermal neutron beam for boron neutron capture therapy.

The application of activation foils, thermoluminescent detectors, and ionization chambers has been investigated for the determination of the different dose components in phantoms irradiated with a mixed gamma-ray and epithermal neutron beam for boron neutron capture therapy. The thermal neutron fluence has been determined using a set of AuAl and MnNi activation foils. TLD-700 and a Mg(Ar) ionization chamber have been used for the determination of the gamma-ray dose. The dose from epithermal neutrons has been determined using a TE(TE) ionization chamber. The detector characteristics and the relative sensitivities of the various detectors to the different dose components in the phantom have been determined. The following accuracies (1 standard deviation) in the determination of the different components have been obtained: thermal neutron fluence rate: 5%; gamma-ray dose rate: 7%; epithermal neutron dose rate: 15%. These values make these detectors suitable for obtaining the complete set of clinical dosimetry data required for patient dose assessment.

Biophysical Phenomena↗
PubMed2005

Epithermal neutron beams for clinical studies of boron neutron capture therapy: a dosimetric comparison of seven beams.

A comparison of seven epithermal neutron beams used in clinical studies of boron neutron capture therapy (BNCT) in Sweden (Studsvik), Finland (Espoo), Czech Republic (ReZ), The Netherlands (Petten) and the U.S. (Brookhaven and Cambridge) was performed to facilitate sharing of preclinical and clinical results. The physical performance of each beam was measured using a common dosimetry method under conditions pertinent to brain irradiations. Neutron fluence and absorbed dose measurements were performed with activation foils and paired ionization chambers on the central axis both in air and in an ellipsoidal water phantom. The overall quality of each beam was assessed by figures of merit determined from the total weighted dose profiles that assumed the presence of boron in tissue. The in-air specific beam contamination from both fast neutrons and gamma rays ranged between 8 and 65 x 10(-11) cGy(w) cm2 for the different beams and the epithermal neutron flux intensities available at the patient position differed by more than a factor of 20 from 0.2-4.3 x 10(9) n cm(-2) s(-1). Percentage depth dose profiles measured in-phantom for the individual photon, thermal and fast-neutron dose components differed only subtly in shape between facilities. Assuming uptake characteristics consistent with the currently used boronated phenylalanine, all the epithermal beams exhibit a useful penetration of 8 cm or greater that is sufficient to irradiate a lesion seated at the brain midline. The performance of the existing facilities will benefit from the introduction of advanced compounds through improved beam penetrability. This could increase by as much as 2 cm for the purest of beams, although the beam intensities generally need to be increased to between 2-5 x 10(9) n cm(-2) s(-1) to maintain manageable irradiation times. These data provide the first consistent measurement of beam performance at the different centers and will enable a preliminary normalization of the calculated patient dosimetry.

Boron Neutron Capture Therapy↗
PubMed1998

Evaluation of useful neutron flux for accelerator boron neutron capture therapy using the 7Li(p,n) reaction.

Accelerator neutron sources for epithermal neutron capture therapy utilising the 7Li(p,n) nuclear reaction are proposed to operate in the range of 1.88 to 2.5 MeV proton energy. Operation with proton energies closer to the reaction threshold decreases neutron yield but allows for smaller reflector and moderator, with less reduction of the epithermal flux, whereas high energies allow thicker targets to be used. The neutron yields for thick lithium targets are estimated in the energy range of 1.881 MeV to 2.5 MeV and useful neutron flux determined. The optimal range of proton energy is found to be 1.89-1.95 MeV, and this is recommended for more detailed studies of neutron transport properties for accelerator BNCT.

Biophysical Phenomena↗
PubMed1979

[Neutron therapy in the GDR. IX. About the accuracy of neutron dosimeter systems (author's transl)].

In this report is specified which accuracies must now be achieved in the determination of dose components for neutron therapy of tumors and for evaluation of RBE's after neutron irradiations of various organs from mammals or men. After these introductory remarks the reasons are summarized why the errors in ionimetric measurements of neutron doses are considerably higher than those of gamma-doses. In detail the concept and the errors of the Rossendorf neutron dosimeter system are represented. The latter consists of two spherical homogeneous ionization chambers, each of which is connected to a commercial dosimeter. The results of an intercomparison between our neutron dosimeter and that of DR. Bewley (MRC Cyclotron Unit, Hammersmith Hospital London) carried out at the Rossendorf neutron therapy facility are reported.

Dose-Response Relationship, Radiation↗
PubMed1995

Dose homogeneity in boron neutron capture therapy using an epithermal neutron beam.

Simulation models based on the neutron and photon Monte Carlo code MCNP were used to study the therapeutic possibilities of the HB11 epithermal neutron beam at the High Flux Reactor in Petten. Irradiations were simulated in two types of phantoms filled with water or tissue-equivalent material for benchmark treatment planning calculations. In a cuboid phantom the influence of different field sizes on the thermal-neutron-induced dose distribution was investigated. Various shapes of collimators were studied to test their efficacy in optimizing the thermal-neutron distribution over a planning target volume and healthy tissues. Using circular collimators of 8, 12 and 15 cm diameter it was shown that with the 15-cm field a relatively larger volume within 85% of the maximum neutron-induced dose was obtained than with the 8- or 12-cm-diameter field. However, even for this large field the maximum diameter of this volume was 7.5 cm. In an ellipsoid head phantom the neutron-induced dose was calculated assuming the skull to contain 10 ppm 10B, the brain 5 ppm 10B and the tumor 30 ppm 10B. It was found that with a single 15-cm-diameter circular beam a very inhomogenous dose distribution in a typical target volume was obtained. Applying two equally weighted opposing 15-cm-diameter fields, however, a dose homogeneity within +/- 10% in this planning target volume was obtained. The dose in the surrounding healthy brain tissue is 30% at maximum of the dose in the center of the target volume. Contrary to the situation for the 8-cm field, combining four fields of 15 cm diameter gave no large improvement of the dose homogeneity over the target volume or a lower maximum dose in the healthy brain. Dose-volume histograms were evaluated for the planning target volume as well as for the healthy brain to compare different irradiation techniques, yielding a graphical confirmation of the above conclusions. Therapy with BNCT on brain tumors must be performed either with an 8-cm four-field irradiation or with two opposing 15- or 12-cm fields to obtain an optimal dose distribution.

Boron Neutron Capture Therapy↗
PubMed2005

The Hiroshima thermal-neutron discrepancy for (36)Cl at large distances. Part I: New (36)Cl measurements in granite samples exposed to A-bomb neutrons.

The long-lived radioisotope (36)Cl (half-life: 301,000 years) was measured in granite samples exposed to A-bomb neutrons at distances from 94 to 1,591 m from the hypocenter in Hiroshima, by means of accelerator mass spectrometry (AMS). Measured (36)Cl/Cl ratios decrease from 1.6 x 10(-10) close to the hypocenter to about 1-2 x 10(-13), at a distance of 1,300 m from the hypocenter. At this distance and beyond the measured (36)Cl/Cl ratios do not change significantly and scatter around values of 1-2 x 10(-13). These findings suggest that the (36)Cl had been predominantly produced by thermalized neutrons from the A-bomb via neutron capture on stable (35)Cl, at distances from the hypocenter smaller than about 1,200 m. At larger distances, however, confounding processes induced by cosmic rays or neutrons from the decay of uranium and thorium become important. This hypothesis is theoretically and experimentally supported in a consecutive paper. The results are compared to calculations that are based on the most recent dosimetry system DS02. Close to the hypocenter, measured (36)Cl/Cl ratios are lower than those calculated, while they are significantly higher at large distances from the hypocenter. If the contribution of the cosmic rays and of the neutrons from the decay of uranium and thorium in the sample was subtracted, however, no significant deviation from the DS02 calculations was observed, at those distances. Thus, the Hiroshima neutron discrepancy reported in the literature for (36)Cl for samples from large distances from the hypocenter, i.e., higher measured (36)Cl/Cl ratios than predicted by the previous dosimetry system DS86, was not confirmed.

Biophysical Phenomena↗
PubMed1990

[Principles of therapy with fission neutrons and boron neutron capture therapy for radioresistant head-neck malignancies].

Neutron therapy has proven to be clinically useful in cases of advanced, slow-growing radioresistant head and neck carcinoma. Therapeutic effects might be based on direct DNA damaging and thus immediate cell-killing, on the generation of free oxygen radicals and, among others, on the fact that heavy particle radiation is said to be less dependent on the presence of oxygen than gamma rays, i.e. on a lower oxygen enhancement ratio (OER). The smaller difference in reaction between oxygenated and nonoxygenated cells could entail advantages as well as disadvantages, depending on the characteristics of the tumor cell population and of the normal tissue. It is therefore essential to select patients and tumours with an expectedly high therapeutic gain factor. Fission neutrons for tumour therapy: As evaluated by several in vitro and in vivo studies (11/13) the biological efficiency (RBE) of the RENT (Reactor Neutron Therapy) beam in Munich seems to be among the highest of all clinically used neutron beams. For a single dose range between 2 and 8 Gy the RBE for chronic radiation damage is relatively small (2). Consequently, patients with recurrent or metastatic carcinomas of the head and neck are treated with a single dose of 200-250 cGy after previous surgery and/or combined radiochemotherapy. The main limitation of fission neutrons is the small penetration depth. Possibilities of clinical implementation of boron neutron capture therapy (BNCT) in otorhinolaryngology: In near surface tumours it is possible to administer high doses of 10boron not selectively, i.e. no selective tumour-seeking compound is needed. Animal experiments with intratumoural injection of 10boron glycine have shown a strong effect on tumour growth delay (18).(ABSTRACT TRUNCATED AT 250 WORDS)

Boron Compounds↗