Methods for dose measurements in small phantoms irradiated at BNCT epithermal column

Suitable dosimeter methods have been proposed and tested, to measure the different dose contributions in small phantoms exposed to epithermal/thermal neutron beams designed for BNCT. One method is based on Fricke-gel dosimeter in small tubes of 2.8 mm of external diameter, that allow determining profiles of gamma dose and of boron dose. The other method is based on the use of TLD-700 chips, from whose answer the contribution of thermal neutrons is subtracted by means of appropriate parameters of the glow curve.     

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.     

Depth-dose measurements of d-T neutrons for radiotherapy applications.

In connection with clinical applications of fast neutrons, depth-dose measurements have been carried out for collimated 15 MeV neutron beams at various source-to-skin distances, using different phantoms of the upper part of the human body. The distribution of fast, thermal and intermediate neutron dose or kerma and gamma dose over the phantoms was determined with tissue-equivalent ionization chambers, gold foils with and without cadmium covers and a shielded Geiger-Müller counter, respectively. In order to determine the tumour dose and the exit dose for the irradiation of patients with pulmonary metastases, depth-dose measurements have been performed for an inhomogeneous phantom containing lung-equivalent material. The measurements indicate a considerable difference in depth dose with respect to the dose distribution in a homogeneous phantom. Measurements with sulphur activation detectors to monitor the exit dose are discussed and compared with the results obtained in the actual patient irradiations.     

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。     

Build-up and depth-dose characteristics of different fast neutron beams relevant for radiotherapy.

Build-up and central axis depth-dose curves have been obtained for d(50) + Be and d + T neutron beams. Measurements carried out with the collimator opening covered with a layer of lead showed that for all three neutron beams the entrance dose is approximately 60% of the dose at the maximum. Consequently the skin-sparing properties of these neutron beams will be approximately equal and comparable to those for electron beam therapy. Central axis depth-dose curves have been established for d(50) + Be neutrons at 129 cm SSD, for p(42) + Be neutrons at 125 cm SSD and d + T neurtons and 60Co gamma rays at 80 cm SSD. The 50% dose values in a water phantom are at depths of 12.7 cm, 12.0 cm, 9.7 cm and 12.7 cm respectively, for field sizes of approximately 15 cm x 20 cm. Insertion of a 6 cm thick nylon filter in the p(42)+Be beam increases this value from 12.0 cm to 13.5 cm. The gamma component for the d+T neutron beam is higher than for the cyclotron beams.     

Photon activation therapy

It is suggested here that significant advantages should accrue from the use of 40 keV photons from implanted sources of 145Sm. These energies should stimulate Auger electron cascades from IdUrd, as well as produce non-repairable damage from radiosensitization. The use of low dose rates (approximately 10 rd/hr) should allow repair in normal tissues exposed to the activating photons. Utilization of this technique with brain tumors should minimize problems associated with radiosensitization of normal tissues, as CNS tissues do not synthesize DNA. The deposition of high LET radiations selectively in tumor cells provides unique advantages not available to either conventional therapy or other forms of particle therapy (fast neutrons, protons, pions, heavy ions).     

Discrimination of various contributions to the absorbed dose in BNCT: Fricke-gel imaging and intercomparison with other experimental results.

A method is described for the 3D measurements of absorbed dose in a ferrous sulphate gel phantom, exposed in the thermal column of a nuclear reactor. The method, studied for Boron Neutron Capture Therapy (BNCT) purposes, allows absorbed dose imaging and profiling, with the separation of different contributions coming from different secondary radiations, generated from thermal neutrons. In fact, the biological effectiveness of the different radiations is different. Tests with conventional dosimeters were performed too.     

The Clatterbridge high-energy neutron therapy facility: specification and performance

A new high-energy neutron therapy facility has been installed at the Douglas Cyclotron Centre, Clatterbridge Hospital, Merseyside, in order to extend the clinical trials of fast neutrons initiated by the Medical Research Council. The neutron beam is produced by bombarding a beryllium target with 62 MeV protons. The target is isocentrically mounted with the potential for 360 degrees rotation and has a fully variable collimator. This gives a range of rectilinear field sizes from 5 cm x 5 cm to 30 cm x 30 cm. Basic neutron beam data including output, field flatness, penumbra and depth-dose data have been measured. For a 10 cm x 10 cm field, the 50% depth dose occurs at 16.2 cm in water and the output is 1.63 cGy microA-1 min-1 at the depth of dose maximum. The effectiveness of the target shielding and the neutron-induced radioactivity in the treatment head have also been measured. It is concluded that the equipment meets both the design specifications and also fully satisfies criticisms of earlier neutron therapy equipment. A full radiation survey of the centre was also carried out and it was found that radiation levels are low and present no significant hazard to staff.     

The interpretation of dose calculations and cell-survival measurements for the boron neutron capture therapy of brain tumours with 24 keV neurons

Monte-Carlo computer codes have been used to estimate the distribution of doses to borated and unborated tissues in head-sized phantoms when exposed to beams of 2 keV and 24 keV neutrons. For the application of such beams to boron neutron capture therapy (BNCT) these calculations show the superiority of 2 keV neutrons over 24 keV neutrons and the importance of using large-area beams. A 24 keV neutron beam has been used to irradiate HeLa cell cultures in vitro, with and without the addition of 10B, at various depths within a narrow polyethylene phantom. Survival data obtained from these experiments have been used to estimate depth-damage profiles for normal (unboronated) and tumour (boronated) brain tissues when exposed to 24 keV neutrons. A good differential between damage to normal and tumorous tissue is obtained under suitable irradiation conditions. Although lower-energy neutrons are probably preferable, these results demonstrate the possibility of using beams of 24 keV neutrons for the BNCT of brain tumours.     

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.     

Accumulation of boron compounds to tumor with polyethylene-glycol binding liposome by using neutron capture autoradiography.

The cytotoxic effect of boron neutron capture therapy (BNCT) is due to a nuclear reaction between 10B and thermal neutrons. It is necessary to accumulate the 10B atoms to the tumor cells selectively for effective BNCT. In order to achieve an accurate measurement of 10B concentrations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of the sliced whole-body samples of tumor bearing mice using CR-39 plastic track detectors. The CR-39 detectors attached with samples were exposed to thermal neutrons in the thermal column of the TRIGA II reactor at the Institute for Atomic Energy, Rikkyo University and thermal neutron facility of Paul Scherer Institute(PSI). We obtained NCAR images for mice injected intravenously by 10B-PEG liposome, 10B-transferrin-PEG liposome, or 10B-bare liposome. The 10B concentrations in the tumor tissue of mice were estimated by means of alpha-track density measurements. In this study, we can increase the accumulation of 10B atoms in the tumor tissues by binding polyethylene-glycol chains to the surface of liposome, which increase the retention in the blood flow and escape the phagocytosis by reticulo-endothelial systems. Therefore, we will be able to apply NCAR technique for selection of effective 10B carrier in BNCT for cancer.     

Dependence of TLD thermoluminescence yield on absorbed dose in a thermal neutron field

The emission from ⁶LiF and ⁷LiF thermoluminescence dosimeters (TLDs) exposed to the mixed field of thermal neutrons and γ-rays of the thermal facility of a TRIGA MARK II nuclear reactor has been investigated for various thermal neutron fluences of the order of magnitude of those utilised in radiotherapy, with the purpose of investigating the reliability of TLD readouts in such radiation fields and of giving some information for better obtainment of the absorbed dose values. The emission after exposure in this mixed field is compared with the emission after γ-rays only. The glow curves have been deconvoluted into gaussian peaks, and the differences in the characteristics of the peaks observed for the two radiation fields, having different linear energy transfers, and for different doses are shown. Irreversible radiation damage in dosimeters having high sensitivity to thermal neutrons is also reported, showing a memory effect of the previous thermal neutron irradiation history which is not restored by anneal treatment.     

Polymer gels for in-phantom dose imaging in radiotherapy

Normoxic polymer gel dosimeters are studied, with the aim of achieving a valid and advantageous method for in-phantom 3D dose determinations. Developments were carried out in the application of such dosimetric material to the method based on dosimeter gel layers that has shown good reliability for absorbed dose imaging in radiotherapy. The technique has been improved, in particular taking care of minimizing the oxygen infiltration into the gel matrix in order to suitably avoid its effect of inhibiting the polymerization process after exposure. A suitable choice of the material of dosimeter walls has brought to achieve good steadiness in time of dosimeter sensitivity and satisfactory results in dose imaging and depth-dose profiling.     

Effects of negative pions and neutrons on the growth of Vicia faba bean roots

Vicia faba bean roots have been irratiated with neutrons of various energies and with negative pi-mesons, and the effect on the ten-day growth of the roots has been determened. The neutron irratiations were made in beams of 400 and 600 MeV maximum energy, as well as with neutrons from a plutonium-beryllium source (mean energy 4.4 MeV) and from a 14 MeV neutron generator. The bean roots have also been irradiated at various points along the depth-dose curve of negative pi-mesons, including the gegion where the pions annihilate on coming to rest. The results show a maximum relative biological effectiveness (RBE) of 3.7 for 50% reduction in ten days growth for stopped negative pions and values up to 3.3 for high-energy neutrons, compared to 5.5 for 14 MeV neutrons. The biological effectiveness of high-energy neutrons and stopped pions shows a more pronounced dependence on dose than does the effect with lower-energy neutrons.     

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.     

A review of boron neutron capture therapy (BNCT) and the design and dosimetry of a high-intensity, 24 keV, neutron beam for BNCT research

This paper reviews the development of boron neutron capture therapy (BNCT) and describes the design and dosimetry of an intermediate energy neutron beam, developed at the Harwell Laboratory, principally for BNCT research. Boron neutron capture therapy is a technique for the treatment of gliomas (a fatal form of brain tumour). The technique involves preferentially attaching 10B atoms to tumour cells and irradiating them with thermal neutrons. The thermal neutron capture products of 10B are short range and highly damaging, so they kill the tumour cells, but healthy tissue is relatively undamaged. Early trials required extensive neurosurgery to exposure the tumour to the thermal neutrons used and were unsuccessful. It is thought that intermediate-energy neutrons will overcome many of the problems encountered in the early trials, because they have greater penetration prior to thermalization, so that surgery will not be required. An intermediate-energy neutron beam has been developed at the Harwell Laboratory for research into BNCT. Neutrons from the core of a high-flux nuclear reactor are filtered with a combination of iron, aluminium and sulphur. Dosimetry measurements have been made to determine the neutron and gamma-ray characteristics of this beam, and to monitor them throughout the four cycles used for BNCT research. The beam is of high intensity (approximately 2 x 10(7) neutrons cm-2 s-1, equivalent to a neutron kerma rate in water of 205 mGy h-1) and nearly monoenergetic (93% of the neutrons have energies approximately 24 keV, corresponding to 79% of the neutron kerma rate).     

Analysis of a discrepancy in electron-beam dose comparison between chemical dosimeters and a calorimeter.

A 2.1% discrepancy was reported from an electron-beam dose comparison between liquid chemical dosimeters and a water calorimeter. Two methods, depth-dose measurement in a sandwich phantom and the use of a semiempirical depth-dose code EDMULT, were used to analyze the depth-dose distribution in the dosimeters and the calorimeter and to calculate their dose ratio. Results have shown that the discrepancy can be explained by the difference in the effective detection volume.     

Gamma/neutron dose evaluation using Fricke gel and alanine gel dosimeters to be applied in boron neutron capture therapy

Gel dosimetry has been studied mainly for medical applications. The radiation induced ferric ions concentration can be measured by different techniques to be related with the absorbed dose. Aiming to assess gamma/thermal neutrons dose from research reactors, Fricke gel and alanine gel solutions produced at IPEN using 300 bloom gelatin were mixed with Na₂B₄O₇ salt, and the mixtures were irradiated at the beam hole #3 of the IEA-R1 research reactor, (BH#3) adapted to BNCT studies, and the dose-response was evaluated using spectrophotometry technique.     

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.     

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%.