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.     

Changes of the cytogenetic effectiveness of the therapeutic ray of fast neutrons in water phantoms

Changes of cytogenetic effectiveness of the therapeutic ray of fast neutrons were studied in water phantom in the Medical-Biological Complex of CyclotronU-120 at the Institute for Nuclear Research of the Academy of Sciences of the Ukrainian SSR. Investigations were done in a culture of lymphocytes of the peripheral human blood by means of metaphase method to find out chromosomal aberrations. The neutrons were generated by firing a thick beryllium target with a 13.6 MeV-deuteron ray in the nuclear reaction 9Be (d,n) 10B. The investigated dose range was 25-220 cGy. The results of the studies demonstrate that the cytogenetic effectiveness of radiation is reduced with increasing depth of the water phantom. The maximum reduction of the effect was seen in a depth up to 6 cm, which is attached to absorption of low-energetic neutron fraction. The obtained results confirm necessity of to filter the therapeutically applicable beam of neutron radiation.     

A fast neutron source for cultured cell irradiation.

Because of recent interest in the use of neutrons for radiotherapy, there has been an increased interest in the radiology of neutrons. In this irradiated cell study, a 1.3 MeV accelerator produced beam currents over 100 muA on the water-cooled 3-mm thick beryllium disk target. The monolayer of irradiated cells was neutron-shielded by about 700 kg of paraffin. The neutron energy spectrum for the 9Be(d,n)10B reaction was obtained, with an average neutron energy calculated to be between 3.3 and 3.5 MeV, and an average linear energy transfer calculated at more than 30 keV/micron.     

Influence of dose rate on fast neutron OER and biological effectiveness determined for growth inhibition in Vicia faba

The influence of dose rate on the effectiveness of a neutron irradiation was investigated using growth inhibition in Vicia faba bean roots as biological system. d(50) + Be neutron beams produced at the cyclotron CYCLONE of the University of Louvain-la-Neuve were used, at high and low dose rate, by modifying the deuteron beam current. When decreasing the dose rate from 0.14 Gy.min-1 to 0.2 Gy.h-1, the effectiveness of the neutrons decreased down to 0.84 +/- 0.05 (dose ratio, at high and low dose rate. Dhigh/Dlow, producing equal biological effect). Control irradiations, with 60Co gamma-rays, indicated a similar reduction in effectiveness (0.84 +/- 0.03) when decreasing dose rate from 0.6 Gy.min-1 to 0.7 Gy.h-1. In previous experiments, on the same Vicia faba system, higher RBE values were observed for 252Cf neutrons, at low dose rate (RBE = 8.3), compared to different neutron beams actually used in external beam therapy (RBE = 3.2 - 3.6 for d(50) + Be, p(75) + Be and 15 MeV (d, T) neutrons). According to present results, this higher RBE has to be related to the lower energy of the 252Cf neutron spectrum (2 MeV), since the influence of dose rate was shown to be small. As far as OER is concerned, for d(50) + Be neutrons, it decreases from 1.65 +/- 0.12 to 1.59 +/- 0.09 when decreasing dose rate from 0.14 Gy.min-1 to 0.2 Gy.h-1. Control irradiations with 60Co gamma-rays have shown an OER decrease from 2.69 +/- 0.08 to 2.55 +/- 0.11 when decreasing dose rate from 0.6 Gy.min-1 to 0.7 Gy.h-1. These rather small OER reductions are within the statistical fluctuations.     

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.     

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.     

Comparison of the effects of neutron and/or photon irradiation on spontaneous squamous-cell carcinoma in mice

The effect of 30MeV D+ leads to Be NIRS cyclotron neutrons on a spontaneous NR-S1 squamous-cell carcinoma was studied. The TD50 (number of tumor cells required for transplantation in half the sites) and tumor growth delay time (TGD) were determined. The RBE of 200-kVp x rays at the 10% survival level was 1.9 for aerobic cells and 2.0 for hypoxic cells; the OER at the same level was congruent to 1.7. Tumor cells irradiated with neutrons were unable to repair potentially lethal damage, in contrast to x-irradiated tumor cells. The RBE of 50-MeV D+ leads to Be neutrons was inversely related to deuteron energy for hypoxic cells. The relationship between TGD and peak skin indicated no benefit from mixed beams or 5 neutron doses.     

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。     

Radiobiological intercomparisons of fast neutron beams used in therapy

A research program was performed at Louvain-la-Neuve to systematically determine the RBE of fast neutrons for the growth inhibition in Vicia faba bean roots and for the regeneration of the intestinal crypts in mice. The following neutron beams were compared p(75) + Be, p(65) + Be, p(45) + Be, p(34) + Be, d(20) + Be, and d(50) + Be. The RBE-variation as a function of neutron energy is larger for the Vicia faba system than for the regeneration of the intestinal crypt cells. This can be related to the inherent differency of the biological systems, but also to the different dose ranges involved (0.33 to 0.56 Gy and 7.66 to 8.56 Gy, respectively). In the high energy range explored, defined by the reactions p(75) + Be to p(34) + Be RBE varies only between 0.92 and 1.28 for Vicia faba and 0.96 and 1.12 for crypt cells normalized to the p(65) + Be beam. By contrast the RBE at lower energy beams (d(20) + Be and d(14.5) + Be) reaches values between 1.5 and 1.6 Finally fractionation has shown to be likely more important at the high energy beams.     

High energy fast neutrons from the Harwell variable energy cyclotron. I. Physical characteristics.

A high energy fast neutron beam potentially suitable for radiotherapy was built at the Harwell variable energy cyclotron. The beam line is described and results are given of physical measurements on the fast neutron beams produced by 42 MeV deuterons on thick (4 mm) and thin (2 mm) beryllium targets. With 20 muA beam current the entrance dose rate in a phantom 150 cm from the target was about 130 rad min-1 with the thick target and about 60 rad min-1 with the thin target. Therefore, it is possible to use both the thin target and the relatively large target-skin distance of 150 cm to improve depth dose for radiotherapy or radiobiology. With this arrangement the dose rate decreased to 50% at depths in the phantom of 11.3-15.4 cm, depending on the field size. The use of primarily hydrogenous materials for shielding and collimation provided beam edge definition similar to that of 60Co teletherapy units, and off-axis radiation levels of approximately 1% which compare favorably with 14 MeV deuteron-tritium generators. The copper backing of the thin target became highly radioactive and an alterative material may be preferable. Biologic characteristics of the beam are described in a companion paper.     

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。     

Towards the final BSA modeling for the accelerator-driven BNCT facility at INFN LNL

Some remarkable advances have been made in the last years on the SPES-BNCT project of the Istituto Nazionale di Fisica Nucleare (INFN) towards the development of the accelerator-driven thermal neutron beam facility at the Legnaro National Laboratories (LNL), aimed at the BNCT experimental treatment of extended skin melanoma. The compact neutron source will be produced via the ⁹Be(p,xn) reactions using the 5 MeV, 30 mA beam driven by the RFQ accelerator, whose modules construction has been recently completed, into a thick beryllium target prototype already available. The Beam Shaping Assembly (BSA) final modeling, using both neutron converter and the new, detailed, Be(p,xn) neutron yield spectra at 5 MeV energy recently measured at the CN Van de Graaff accelerator at LNL, is summarized here.     

Neutron dosimetry intercomparisons between National Accelerator Centre, Université Catholique de Louvain and Clatterbridge Hospital

Neutron dosimetry intercomparison studies have been undertaken at three neutron therapy facilities which have similar beam characteristics; viz. National Accelerator Centre, South Africa [p(66 MeV)+Be], Université Catholique de Louvain, Belgium, [p(65 MeV)+Be] and MRC Cyclotron Unit, Clatterbridge Hospital, U. K. [p(62 MeV)+Be]. The procedures followed at all centres were the same: tissue equivalent (TE) ionization chambers were first calibrated in 60Co beams and then exposed under various conditions in the respective neutron therapy beams. Measurements were made with the chambers flushed with TE gas or filled with static air. The neutron beam measurements differed by a maximum of 2.4%, whereas if only one particular type of ionization chamber is considered the spread in values is reduced to +/- 0.5%. The TE gas/air response ratios are consistent with calculated values. The results obtained are highly satisfactory and confirm that the dosimetry procedures adopted by the participating institutes conform to international standards.     

The RENT-project: radiobiological results and planned clinical application

Various preclinical tests have been performed to determine the properties of fast neutrons of a mean energy of 2 MeV produced by an U-235 converter plate in the research reactor of the Technical University of Munich. Experiments have been carried out using two specific beams denoted as RENT I and RENT II (RENT stands for Reaktor Neutron Therapy). RENT II is the unmodified beam with a dose rate of 65 rd/min and a gamma-contamination of nearly 50% in 2 cm depth of a perspex phantom. In RENT I the gamma-component is reduced to 25% after filtration of the beam with 2.5 cm lead, whereas the total dose rate is reduced to 22 rd/min.     

A novel vertebrate system for the examination and direct comparison of the relative biological effectiveness for different radiation qualities and sources

Purpose: The recent rapid increase of hadron therapy applications requires the development of high performance, reliable in vivo models for preclinical research on the biological effects of high linear energy transfer (LET) particle radiation.

Aim: The aim of this paper was to test the relative biological effectiveness (RBE) of the zebrafish embryo system at two neutron facilities.

Material and Methods: Series of viable zebrafish embryos at 24-hour post-fertilization (hpf) were exposed to single fraction, whole-body, photon and neutron (reactor fission neutrons (<En?=?1?MeV>) and (p (18?MeV)+Be, <En>?=?3.5?MeV) fast neutron) irradiation. The survival and morphologic abnormalities of each embryo were assessed at 24-hour intervals from the point of fertilization up to 192 hpf and then compared to conventional 6?MV photon beam irradiation results.

Results: The higher energy of the fast neutron beams represents lower RBE (ref. source LINAC 6?MV photon). The lethality rate in the zebrafish embryo model was 10 times higher for 1?MeV fission neutrons and 2.5 times greater for p (18?MeV)+Be cyclotron generated fast neutron beam when compared to photon irradiation results. Dose-dependent organ perturbations (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, pericardial edema and inhibition of yolk sac resorption) and microscopic (marked cellular changes in eyes, brain, liver, muscle and the gastrointestinal system) changes scale together with the dose response.

Conclusion: The zebrafish embryo system is a powerful and versatile model for assessing the effect of ionizing radiation with different LET values on viability, organ and tissue development.     

Changes in relative biological effectiveness with depth of the Clatterbridge neutron therapy beam

We have measured the biological equivalence of the Clatterbridge neutron therapy beam [p(62)-Be] and the Hammersmith neutron therapy beam [d(16)-Be] using the mouse intestinal crypt assay. The ratio (NDR) of Clatterbridge neutron (n + gamma) dose relative to Hammersmith neutron dose (n + gamma) was found to be 1.2-1.13 over a dose/fraction range of 1.8-9 Gy at 2 cm deep in a Perspex phantom. It is shown that the effectiveness of the Clatterbridge beam was reduced with penetration into the phantom because of hardening of the beam to a maximum reduction of 11% at 12 cm deep in the phantom. The hardening of the beam with depth of penetration will need to be taken into account by clinicians in assessing the tumour dose and tissue tolerance. Relative biological effectiveness values for the Clatterbridge and Hammersmith neutron beams were also measured. All neutron doses for both Hammersmith and Clatterbridge beams are total doses (n + gamma) which comply with the European protocol for neutron dosimetry and include the gamma-ray component of dose.     

Changes in biological effectiveness of the neutron beam at Clatterbridge (62 MeV p on Be) measured with cells in vitro

Chinese hamster V79 cells have been used to assess changes in RBE of the p(62)Be neutron beam at the Clatterbridge Hospital with depth in a phantom and with use of a hydrogenous filter. The cells were exposed at depths of 2 and 12 cm and at a depth of 2 cm with a hydrogenous filter. Two groups of experimenters each conducted two experiments. The ratios of relative biological effectiveness (RBE) at a depth of 12 cm to that at 2 cm were found by the two groups to be 0.99 +/- 0.04 and 0.96 +/- 0.02 (standard errors). The effect of a polythene filter 4.5 cm thick was measured at a depth of 2 cm and the ratio of RBE with and without the filter was found by both groups to be 0.99 +/- 0.02. All the experiments suggest that there may be small effects of beam hardening by depth and filtration but these results are in marked contrast with those obtained using an in vivo system.     

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.     

Characterization of ultra high energy neutron beam generated by 500 MeV proton beam

An ultra high energy neutron facility was constructed at PARMS, University of Tsukuba, to produce a neutron beam superior to an X-ray beam generated by a modern linac in terms of dose distribution. This has been achieved using the reaction on a thick uranium target struck by 500 MeV proton beam from the booster-synchrotron of High Energy Physics Laboratory. The percentage depth dose of this neutron beam is nearly equivalent to that of X-rays at around 20 MV and the dose rate of 15 cGy per minute. Relative biological effectiveness of this neutron beam has been estimated on the cell killing effect by the use of HMV-I cell line. Resultant survival curve of cells after the neutron irradiation shows the shoulder with n and Dq of 8 and 2.3 Gy, respectively. RBE value at 10(-2) survival level for the present neutron, compared with 137Cs gamma-rays is 1.24. The result suggests that the biological effects of high energy neutrons are not practically large enough whenever the depth dose distribution of neutrons becomes superior to high energy linac X-rays.     

High-power liquid-lithium target prototype for accelerator-based boron neutron capture therapy

A prototype of a compact Liquid-Lithium Target (LiLiT), which will possibly constitute an accelerator-based intense neutron source for Boron Neutron Capture Therapy (BNCT) in hospitals, was built. The LiLiT setup is presently being commissioned at Soreq Nuclear Research Center (SNRC). The liquid-lithium target will produce neutrons through the ⁷Li(p,n)⁷Be reaction and it will overcome the major problem of removing the thermal power generated using a high-intensity proton beam (>10 kW), necessary for sufficient neutron flux. In off-line circulation tests, the liquid-lithium loop generated a stable lithium jet at high velocity, on a concave supporting wall; the concept will first be tested using a high-power electron beam impinging on the lithium jet. High intensity proton beam irradiation (1.91–2.5 MeV, 2–4 mA) will take place at Soreq Applied Research Accelerator Facility (SARAF) superconducting linear accelerator currently in construction at SNRC. Radiological risks due to the ⁷Be produced in the reaction were studied and will be handled through a proper design, including a cold trap and appropriate shielding. A moderator/reflector assembly is planned according to a Monte Carlo simulation, to create a neutron spectrum and intensity maximally effective to the treatment and to reduce prompt gamma radiation dose risks.