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.     

RBE and OER measurements on the p(66) + Be neutron beam at Faure, South Africa.

Results reported are for single dose exposures and refer to 60Co-gamma-irradiation. The RBE determined by V79 cell survival and based on the Do ratio was found to be 1.70 +/- 0.4 ranging from 1.5 to 1.8. In the case of the regeneration of mouse jejunal crypts the RBE was calculated at ten cell survival and was found to be 1.68. The maximum acute mouse skin reaction at a skin score of 2.0 was found to be 2.1 while the average skin reaction was 1.7. Growth retardation of Vicia faba bean roots measured at the level of 50% indicated an average RBE of 3.0 and a range of 2.7 to 3.7. The OER obtained for V79 cell survival was found to be 1.7 to 1.8. Comparison is made with the RBE and OER measurements for the neutron facilities at Clatterbridge, Fermilab and Louvain-la-Neuve which produce neutrons by the same nuclear reaction and whose physical specifications closely resemble those of the Faure neutrons. This comparison indicates that the Faure beam shows no unusual biological features and that its biological effectiveness is in line with that expected from its physical characteristics.     

Radiobiological analysis of human melanoma cells on the 62 MeV CATANA proton beam

PURPOSE: To measure the ability of protons and gamma-rays to effect cell viability and cell survival of human HTB140 melanoma cells. MATERIALS AND METHODS: Exponentially growing HTB140 cells were irradiated close to the Bragg peak maximum of the 62 MeV protons or with 60Co gamma-rays with single doses, ranging from 8 - 24 Gy. Cell viability using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay was evaluated at 6 h, 24 h, 48 h or 7 days after irradiation and clonogenic survival was assessed at 7 days after irradiation. Cell cycle phase redistribution and the level of apoptosis were evaluated at 6 h and 48 h after irradiation. RESULTS: The study of cell viability as a function of time (cell survival progression) and cell survival, using a clonal assay, demonstrated the considerably stronger inactivation effect of protons compared to gamma-rays with a relative biological effectiveness (RBE) of approximately 1.64. Cell cycle phase distribution and apoptosis levels with time enabled us to investigate the development and the character of the damage induced by irradiation. Due to the high radio-resistance of HTB140 cells, cell cycle phase redistribution exhibited only a modest cell accumulation in G2/M phase. Protons but not gamma-rays induced apoptosis. CONCLUSIONS: It appears that protons reduce the number of HTB140 cells by apoptosis as well as by severe DNA damage, while gamma-rays eliminate viable cells primarily by the production of irreparable DNA damage. Protons have an increased RBE relative to gamma-rays.     

Relative biological effectiveness (RBE) of p(26) + Be neutrons from the King Faisal Specialist Hospital and Research Centre CS-30 cyclotron measured by testis weight loss

Testis weight loss of C3H and Swiss-Webster (SW) mice was used as endpoint to determine the relative biological effectiveness (RBE) of p(26) + Be fast neutrons with respect to Co-60 gamma irradiation. Percent weight loss versus dose curves showed two components. Comparing first component effects, the RBE was 3.4 (C3H) and 3.7 (SW); when the second component was used, the RBE was 2.6 and 2.7 (C3H), and 3.5 (SW). When percent weight loss was plotted versus log dose, parallel lines were obtained, giving an RBE of 3.9 and 4.1 (C3H), and 4.2 (SW). Results were compared with published values and RBE as a function of fast neutron energy was plotted. A good correlation was found. Discrepancies seem to be mostly due to the use of different baseline radiation. When a constant correction is made, most of the values fit a single line. The possibility of using this approach as a substitute for international comparisons is discussed.     

Experimental study of the relative biological effectiveness (R.B.E.) of a fast neutron beam (author's transl)

A preliminary experimentation has been done with the synchrocyclotron (28 MeV deuton) in Lyon. The different characteristics of the beam have been determined through various dosimetric measurements. C57Bl mice have been irradiated with single doses and fractionated schedules (5 sessions). 7 day survival has been analysed. Comparison of neutron and cobalt gamma ray shows a R.B.E. of 1.95 for single dose and 2.5 for five fractions. This work is a confirmation of the effect of fractionation on the R.B.E. of the neutrons.     

Cross sections of (n,p), (n,alpha) and (n,2n) reactions on some isotopes of zirconium in the neutron energy range of 10-12 MeV and integral tests of differential cross section data using a 14 MeV d(Be) neutron spectrum.

Cross sections were measured for the 90Zr(n,alpha)87mSr, 90Zr(n,2n)89m,gZr, 91Zr(n,p)91mY, 92Zr(n,p)92Y, 94Zr(n,alpha)91Sr and 96Zr(n,2n)95Zr reactions over the neutron energy range of 11.4 to 12.4 MeV and for the 94Zr(n,p)94Y reaction from 9.2 to 12.4 MeV. Nuclear model calculations were performed up to 16MeV. The statistical model incorporating precompound effects reproduces excitation functions of the three major threshold reactions, namely (n,p), (n,alpha) and (n,2n), quite well. Spectrum averaged cross sections were measured using a thick target Be(d,n) neutron field at Ed = 14 MeV. For the same neutron field averaged reaction cross sections were deduced using the excitation functions measured in this work as well as those given in the ENDF/B-VI, JEF-2, JENDL-3.2, BROND and ADL-3 data files. A comparison of the experimental and deduced integral data helped validating the differential data.     

Investigation of the natZn(p,x)62Zn nuclear process up to 70 MeV: a new 62Zn/62Cu generator

The excitation function of the ^natZn(p,x)⁶²Zn nuclear process was measured by the stacked-foil technique up to a proton energy of 70 MeV to obtain accurate data for production of the ‘mother nuclide’ (⁶²Zn) of the PET related β⁺ emitting radioisotope ⁶²Cu. Investigations were also made on the ⁶⁶Zn(p,x)⁶²Zn and ^natZn(p,xn)⁶⁶Ga processes and on the ⁶⁶Zn(p,n)⁶⁶Ga reaction using ^natZn and highly enriched ⁶⁶Zn. The excitation functions were compared with the published data. Thick target yields for the ^natZn(p,x)⁶²Zn and ^natCu(p,xn)⁶²Zn processes were also calculated up to 70 MeV. On the basis of these calculations the ^natZn+p process results in higher yield for ⁶²Zn above 50 MeV than the ^natCu+p process. The latter process is presently used for practical production of ⁶²Zn. In an energy window from 70 to 30 MeV the available EOB yield of the ^natZn+p reactions is around 19 mCi/μA h (0.7 GBq/μAh) that makes the ^natZn(p,x)⁶²Zn process a good candidate for routine generator production.     

Radiobiological studies on the 65MeV therapeutic proton beam at Nice using human tumour cells

Purpose : To determine the relative biological effectiveness (RBE) for initial and delayed inactivation of cells by a modulated proton beam suitable for the treatment of tumours of the eye, within the spread-out Bragg peak and in its distal declining edge. Materials and methods : Human tumour SCC25 cells were irradiated with the 65 MeV proton beam at the Cyclotron Medicyc in Nice. Perspex plates of different thickness were used to simulate five positions along the beam line: 2 mm corresponding to the entrance beam; 15.6 and 25mm in the spread-out Bragg peak; 27.2 and 27.8mm for the distal edge. At each position clonogenic survival of the irradiated cells and of their progeny were determined at various dose values. 60 Co γ-rays were used as reference radiation. Results : RBE values evaluated at the survival level given by 2 Gy of γ-rays increased with increasing depth from close to 1.0 at the proximal to about 1.2 at the distal part of the peak. Within the declining edge it reached the value of about 1.4 at 27.2 and about 2 at 27.8 mm. For the progeny of irradiated cells, the RBE value ranged from 1.0 to 1.1 within the spread-out Bragg peak and then increased up to a value of 2.0 at the last position. The dose-effect curves for the progeny always had a larger shoulder than for the irradiated progenitors, their α parameters being lower by a factor of about 4 and their β parameters always being higher. The alpha/beta ratio was about 50Gy for the progenitors and about 6Gy for their progeny. The incidence of delayed eÚects increased with dose and with the depth within the beam. Conclusions : RBE values for the inactivation of cells irradiated in the spread-out Bragg peak are compatible with the value currently assumed in clinical applications. In the distal declining edge of the beam, the RBE values increased significantly to an extent that may be of concern when the region of the treatment volume is close to sensitive tissues. The yield of delayed reproductive cell death was significant at each position along the beam line.     

Radiobiological studies on the 65 MeV therapeutic proton beam at Nice using human tumour cells

PURPOSE: To determine the relative biological effectiveness (RBE) for initial and delayed inactivation of cells by a modulated proton beam suitable for the treatment of tumours of the eye, within the spread-out Bragg peak and in its distal declining edge. MATERIALS AND METHODS: Human tumour SCC25 cells were irradiated with the 65 MeV proton beam at the Cyclotron Medicyc in Nice. Perspex plates of different thickness were used to simulate five positions along the beam line: 2mm corresponding to the entrance beam; 15.6 and 25 mm in the spread-out Bragg peak; 27.2 and 27.8mm for the distal edge. At each position clonogenic survival of the irradiated cells and of their progeny were determined at various dose values. 60Co gamma-rays were used as reference radiation. RESULTS: RBE values evaluated at the survival level given by 2 Gy of gamma-rays increased with increasing depth from close to 1.0 at the proximal to about 1.2 at the distal part of the peak. Within the declining edge it reached the value of about 1.4 at 27.2 and about 2 at 27.8 mm. For the progeny of irradiated cells, the RBE value ranged from 1.0 to 1.1 within the spread-out Bragg peak and then increased up to a value of 2.0 at the last position. The dose-effect curves for the progeny always had a larger shoulder than for the irradiated progenitors, their alpha parameters being lower by a factor of about 4 and their beta parameters always being higher. The alpha/beta ratio was about 50 Gy for the progenitors and about 6 Gy for their progeny. The incidence of delayed effects increased with dose and with the depth within the beam. CONCLUSIONS: RBE values for the inactivation of cells irradiated in the spread-out Bragg peak are compatible with the value currently assumed in clinical applications. In the distal declining edge of the beam, the RBE values increased significantly to an extent that may be of concern when the region of the treatment volume is close to sensitive tissues. The yield of delayed reproductive cell death was significant at each position along the beam line.     

肿瘤细胞对p(35)Be快中子的辐射敏感性研究

目的 比较肿瘤细胞p(35)Be块中子及γ射线的辐射敏感性,为肿瘤的快中子治疗提供理论依据。方法 用细胞集落在存活方法研究人黑色素瘤细胞（WM9839）、人口 皮癌细胞（KB）、人结肠腺癌细胞（LS－T－117）和人前列腺癌细胞（PC3M）等4种细胞对快中子及γ射线的辐射敏感性,用彗星电泳技术研究WM9839细胞在快中子及γ射线照射后DNA损伤的修复效应。结果 细胞存活实验表明,p(35)Be快中子照射后4种肿瘤细胞的D0值（或SF2值）较γ射线照射后差异减小,即4种肿瘤细胞对快中子的辐射敏感性差异减小;快中子2Gy照射后,WM9839细胞DNA损伤修复曲线整体上下降较γ射线2Gy照射后慢,到180min时,DNA损伤残留率明显高于γ射线2Gy照射。结论 快中子治疗肿瘤可以很好地弥补低LET射线放射治疗的不足,特别是对低LET射线较为耐受的肿瘤细胞,如KB细胞和WM98309细胞。     

The effect of an analyzed deuterium ion beam on the lifetime of TiT targets used at the fast neutron therapy facility (DT, 14 MeV) Hamburg-Eppendorf.

Report on experiments performed with mixed or analyzed deuterium ion beams incident on TiT targets at the neutron therapy facility Hamburg-Eppendorf. Bombarding a TiT target area with all separated atomic and molecular ions of an analyzed deuterium ion beam at different beam spots, the "initial" half-life of the used tritium target increases with a factor of more than three as against the half-life obtained with a mixed deuterium ion beam at a single beam spot. In this case, the effective target current is not reduced and in the same order as that for a mixed deuterium ion beam. Using the atomic deuterons only, the increase of the "initial" half-life is far longer yet, but the loss in target current is about 50% dependent on the reduction of molecular deuterium ions. These facts are most important for the economy of this type of neutron therapy facilities clinical work.     

Excitation functions of natZn(p,x) nuclear reactions with proton beam energy below 18 MeV

We measured the excitation functions of ^natZn (p,x) reactions up to 17.6 MeV, using the stacked-foils activation technique. High-purity natural zinc (and copper) foils were irradiated with proton beams generated by an 18 MeV isochronous cyclotron. Activated foils were measured using high-purity Ge gamma spectroscopy to quantify the radionuclides ⁶¹Cu, ⁶⁶Ga, ⁶⁷Ga, and ⁶⁵Zn produced from the reactions. Thick-target integral yields were also deduced from the measured excitation functions of the produced radioisotopes. These results were compared with the published literature and were found to be in good agreement with most reports, particularly those most recently compiled.     

AB-BNCT beam shaping assembly based on 7Li(p,n)7Be reaction optimization

A numerical optimization of a Beam Shaping Assembly (BSA) for Accelerator Based-Boron Neutron Capture Therapy (AB-BNCT) has been performed. The reaction ⁷Li(p,n)⁷Be has been considered using a proton beam on a lithium fluoride target. Proton energy and the dimensions of a simple BSA geometry have been varied to obtain a set of different configurations. The optimal configuration of this set is shown.     

Response of normal BALB/c mouse tissue to p(66 MeV)/Be fast neutron radiation: protection by exogenous ATP.

Exogenous ATP administered by intraperitoneal injection of 700 mg/kg has been used to provide radioprotection of BALB/c mice after a lethal dose of whole body irradiation (6 Gy). This comprised the beam from a neutron therapy facility produced by the reaction p(66 MeV)/Be. Survival of the mice, using 30 days post-irradiation as the endpoint, was increased from 40% to 85% by action of the exogenous ATP. Furthermore, ATP's glucoregulatory effects, which modify basal physiological regulatory processes were studied in the testes and caused significant augmentation in the activities of the glycolytic enzymes hexokinase and lactate dehydrogenase when compared with neutron radiation alone. Finally ATP reduced the activity of testicular acid phosphatase, an indicator of lytic processes in the tissues damaged. These radioprotection actions in BALB/c mice reflect an adaptive defence mechanism to maintain homeostasis in response to the radiation injury.     

The neutron therapy facility (DT, 14 MeV) at the radiotherapy department of the university hospital Hamburg-Eppendorf

The neutron therapy facility at the Radiotherapy Department of the University Hospital Hamburg-Eppendorf is described. This unit has been developed for clinical purposes according to the initiative and conception of the radiotherapist by AEG/Fed. Rep. of Germany and RDI/USA since 1969. The installation was completed at the beginning of 1974. Special treatment head and bed systems allow isocentric treatment and arc or multiple port therapy. For routine work operation conditions of 8 to 12 mA total beam current and 500 kV accelerating voltage are used. The neutron output at 12 mA is about 3.5 x 10(12) n/s giving a phantom dose rate of more than 20 rad/min for a field size of 17.8 x 17.8 cm2 at 80 cm source-skin distance. Technical installations for improvement of dose rate and half-life of the target are planned. Results of physical measurements about neutron energy distributions, contributions from neutrons and gamma-rays to the total absorbed dose, build-up effect, axial and lateral dose distributions as well as isodose profiles for different field sizes in a homogeneous phantom are presented. Bewteen February 1976 and November 1977 up to 180 patients have been treated.