Clinical study of relative biological effectiveness for cervical carcinoma treated by 252Cf neutrons and assessed by histological tumour eradication

Clinical data of the University of Kentucky trial using californium (252Cf), or caesium (137Cs), are reviewed for dose-response based on the endpoint of tumour eradication estimated from hysterectomy specimens obtained 4-6 weeks after preoperative irradiation. These data are used to assess the relative biological effectiveness (RBE) for 252Cf neutrons compared with 137Cs gamma radiation. Tumours treated were of common stage but were of bulky or barrel shape suitable for "radiosurgical" therapy. Dose-response curves were constructed, and additional data from the literature used to analyse the curve shape. The photon dose-response curve is complex on a logarithmic plot, whereas the 252Cf neutron curve is exponential. This indicates that the RBE can be different depending on the number of implants, schedule and size of dose delivered per session. The RBE values were approximately 8.0 at low doses or for multiple implants but they may rise to approximately 16 at larger doses or for single 252Cf implants.     

Relative biological effectiveness of low- and high-LET radiotherapy beams for jejunal crypt cell survival at low doses per fraction.

In order to determine the relative biological effectiveness (RBE) of various low- and high-LET radiotherapy beams of low coses, LAF1 mice were exposed to one dose and 10 equally fractionated doses of 60Co gamma rays, 137Cs gamma rays, 4-MeV x rays, 300-kVp x rays, helium ions in the plateau and Bragg-peak region, and 15-MeV neutrons; survival of jejunal crypt cells with the microcolony assay of Withers and Elkind was determined using 60Co as the standard. RBE values for the survival of 10 cells/circumference for 10 fractionated exposures (2.4 Gy [240 rad] per fraction of 60Co) were: 1.07 for 137Cs, 1.06 for 4-MeV x rays, 1.16 for 300-kVp x rays, 1.10 for helium ions in the plateau, 1.29 for helium ions in the peak, and 3.02 for 15-MeV neutrons. As LET increased, RBE increased with decrease of dose/fraction.     

Radiosensitivity of C. Parvum-stimulated Spleen to Acute 60Co and Low Dose Rate 137Cs and 252Cf Irradiation

Summary

Stimulation of spleen growth by injection of C. parvum led to rapid organ enlargement, and acute ⁶⁰Co or low dose rate (LDR) ¹³⁷Cs or ²⁵²Cf irradiation reduced the maximum enlargement achieved. Irradiations were carried out 3 days after CP injection. Sigmoid dose–response curves were observed for the fraction of maximum enlargement achieved after acute ⁶⁰Co. After low dose rate ¹³⁷Cs or ²⁵²Cf irradiation, exponential dose-response curves of very different slope were observed. Acute and LDR γ-radiation produced reduced effects in the stimulated and proliferating spleen compared to LDR ²⁵²Cf neutron/γ-irradiation which had relative biological effectiveness = 4·0 versus low dose rate ¹³⁷Cs.     

不同传能线密度射线0~1Gy照射诱发染色体畸变的量-效关系研究

目的 建立0~1Gy范围内⁶⁰Coγ射线、 ²⁵²Cf 中子、单能中子及 ¹²C 重离子诱发染色体畸变剂量-效应曲线,用于评价职业受照或低剂量辐射损伤。方法 采用不同照射装置1Gy以内照射离体人外周血,于培养开始加秋水仙素,培养48h收获,制备染色体标本,Metafer中期细胞自动寻找系统,人机交互计数染色体畸变,最优拟合数据得到相应模型。结果 在低剂量范围内,以双着丝粒体+环(dic+r)为终点,⁶⁰Coγ射线为线性模型, ²⁵²Cf 中子、单能中子及 ¹²C 重离子为线性平方模型;以无着丝粒断片(ace)为终点,⁶⁰Coγ射线和 ¹²C 重离子为线性平方模型, ²⁵²Cf 中子和单能中子为线性模型;以总畸变为终点,4种射线均为线性平方模型。结论 高传能线密度(LET)射线损伤效应高于低LET射线,4种射线损伤效应依次为 ²⁵²Cf 混合中子 >单能中子> ¹²C 重离子> ⁶⁰Co γ射线。在低剂量范围内dic+r指标适用于高LET照射的剂量估算。     

Sperm Shape Abnormalities in Mice Exposed to Californium-252 Radiation

Summary

Male mice of the B6C3F1 hybrid strain were whole-body irradiated with different doses of ²⁵²Cf/⁶⁰Co. They were killed 35 days later and spermatozoa from cauda epididymides were stained with eosin-Y. The air-dried smears were examined under light microscope for sperm shape abnormalities. There was an increase in the frequency of abnormal sperm in all the treated groups compared to controls. The RBE for the mixed neutron and gamma radiation of ²⁵²Cf was 2·6. The RBE for the neutron component was 3·4. The increased frequency of abnormal sperm was associated with a concomitant decrease in testis weight in the irradiated animals.     

Californium-252 (252Cf) versus Conventional Gamma Radiation in the Brachytherapy of Advanced Cervical Carcinoma

BACKGROUND: When photon radiotherapy is applied to cervical carcinoma, it has been observed that, despite important progress in radiotherapy technique and quality assurance, no significant increase in curative rates has resulted. Among the reasons for this is the varying radiosensitivity of different tumor subpopulations. Treatment with californium-252 ((252)Cf), as a source of gamma/neutron radiation in brachytherapy, provides properties and new treatment modalities that help to overcome this factor. PATIENTS AND METHODS: From January 1985 to June 1993, 227 women with stage IIB and IIIB cervical carcinoma were treated in a randomized brachytherapy study as follows: (1) 117 patients (55 with stage IIB, 62 with stage IIIB) were treated with (252)Cf during the 1st week of therapy by 6 Gy (40 Gy-eq) of the neutron component in point A. Supplementation by a 16-Gy dose with (226)Ra or (137)Cs was done in the 5th week. (2) 110 patients (50 with stage IIB, 60 with stage IIIB) were treated solely by gamma radiation ((226)Ra or (137)Cs). A dose of 56 Gy in point A was applied in two fractions at the 3rd and 5th week, respectively. The dose of 56 Gy-equivalents was completed by external radiation with 40 Gy. The total radiation doses at points A and B amounted to 85 Gy and 59 Gy, respectively. The treatment results were compared. RESULTS: The overall 5-year survival rate for all stages IIB and IIIB was better by 18.9% for (252)Cf patients than for patients receiving conventional treatment (75.2% vs. 56.3%, respectively; p < 0.001). In the stage IIIB (252)Cf group, it was significantly better by 22.8% than for the conventional group (66.1% vs. 43.3%, respectively; p < 0.003). The higher survival rate in (252)Cf patients was the result of significantly less local relapses compared with patients treated conventionally (12,8% vs. 31.8%; p < 0.0009). CONCLUSION: The importance of neutron source (252)Cf in the brachytherapy of cervical carcinoma by overcoming the tumor resistance to conventional photon irradiation has been confirmed.     

Comparison of the TL responses of two different preparations of LiF:Mg,Cu,P irradiated by photons of various energies.

The aim of this work is to present the results concerning the photon irradiation of a new phosphor, the LiF:Mg,Cu,P+PTFE, produced at the Instituto Nacional de Investigaciones Nucleares (ININ-Mexico). The photon irradiations were performed using X-rays of 16, 24, 34.5, 42, 100 and 145keV, and gamma rays from (137)Cs (662keV) and from (60)Co (1 252keV). The results obtained are normalized to the (60)Co response. The experimental data are then compared to those obtained using the commercial dosimeters TLD-100 and GR-200A.     

Soft X-ray dosimetry and RBE for survival of Chinese hamster V79 cells

Dosimetry and biological effects of 40 and 50 keV low-energy X-rays generated by a SOFTEX Model CMBW-2 apparatus were studied. Doses were measured using a thin-window parallel-plate ionization chamber; beam quality was assessed using aluminum absorbers; exposure rates per unit current were determined according to the X-ray tube current and exposure times; and thermoluminescent (BeO chip) dosimeters were used to ascertain dose distributions in the irradiation field. The average correction factors for nonuniformity were calculated from the measured dose distributions. The means for ascertaining accurate exposures and doses using these methods are discussed. The dose-survival relationship of Chinese hamster V79 cells were assessed by irradiating them with 40 and 50 kV soft X-rays, 180 kV X-rays, and 60 Co gamma rays. Soft X-rays with three distinct effective energies were tested by changing the tube voltage kV and aluminium filter thicknesses; namely (1) 40 kV without filter, (2) 40 kV with a 0.2 mm thick aluminium filter and (3) 50 kV with a 0.7 mm thick aluminium filter. The effective energies obtained according to attenuation measurements using aluminium for these soft X-rays were 8.1, 11.7 and 18.5 kV, respectively. In this study the relative biological effectiveness (RBE) at 10 per cent survival compared with 60Co gamma rays ranged from 1.5 to 1.6. The RBE of 180 kV X-rays relative to 60Co gamma rays was 1.29. This study provided experimental data for the RBE of V79 cells in the intermediate energy range between hard and ultrasoft X-rays, data for which were previously reported by Goodhead and co-workers (1977, 1979, 1981).     

Increased 252Cf therapeutic advantage for an advanced murine lymphoma (LSA) growing in vivo

The relative biological effectiveness (RBE) was determined for 252Cf irradiation of the murine LSA lymphoma growing in vivo. Irradiation was performed on Days 1-3, i.e. on the young and rapidly growing tumour, on Day 5, i.e. the early stationary phase, or on Day 7, i.e. the advanced tumour. Mice inoculated with 10(5) cells would die on about Day 9 with disseminated tumour if untreated. Irradiation with acute 60Co or low-dose-rate 252Cf total-body irradiation increased the mean survival time (MST). For 252Cf the MST increased linearly with dose, the effectiveness being independent of the day of irradiation. For 60Co, the MST increased linearly with dose for the tumours irradiated on Days 1-3 but two-component curves were noted after irradiation on Days 5-7. Tumour response showed an increasing photon-resistant component which gave no increase in MST with dose. The RBE was approximately 4 for the early tumours but was greater than 5 for the advanced and more photon-resistant tumours. 252Cf was effective for the treatment of early or advanced stages but was especially effective against the advanced, more radioresistant tumours.     

Tumor induction in mice after local irradiation with single doses of either carbon-ion beams or gamma rays

Abstract

Purpose: To determine the dose-dependent relative biological effectiveness (RBE) for tumor prevalence in mice receiving single localized doses to their right leg of either carbon ions (15, 45 or 75 keV/μm) or 137Cs gamma rays.

Methods and materials: A total of 1647 female C3H mice were irradiated to their hind legs with a localized dose of either reference gamma rays or 15, 45 or 75 keV/μm carbon-ion beams. Irradiated mice were evaluated for tumors twice a month during their three-year life span, and the dimensions of any tumors found were measured with a caliper. The tumor induction frequency was calculated by Kaplan-Meier analysis.

Results: The incidence of tumors from 50 Gy of 45 keV/μm carbon ions was marginally higher than those from 50 Gy of gamma rays. However, 60 Gy of 15 keV/μm carbon ions induced significantly fewer tumors than did gamma rays. RBE values of 0.87 + 0.12, 1.29 + 0.08 or 2.06 + 0.39 for lifetime tumorigenesis were calculated for 15, 45 or 75 keV/μm carbon-ion beams, respectively. Fibrosarcoma predominated, with no Linear Energy Transfer (LET)-dependent differences in the tumor histology. Experiments measuring the late effect of leg skin shrinkage suggested that the carcinogenic damage of 15 keV/μm carbon ions would be less than that of gamma rays.

Conclusions: We conclude that patients receiving radiation doses to their normal tissues would face less risk of secondary tumor induction by carbon ions of intermediate LET values compared to equivalent doses of photons.     

On the difference between reference radiations used in radiobiology

Purpose: To add further support to the designation of hard gamma‐rays, such as those emitted by ⁶⁰Co or ¹³⁷Cs, as the common reference radiation, as recommended by the International Commission on Radiological Protection (ICRP) Task Group 37 in the recent ICRP Publication 92.

Materials and methods: The study examined the microdosimetric properties of seven commonly used reference radiations and quantified differences in radiation quality among them. The principal tool is the proximity function, which is derived from the spatial distributions of energy deposits calculated by Monte Carlo simulations.

Results: The microdosimetric properties of the seven commonly used reference radiations were significantly different. However, there were no significant differences in the spectra of energy deposition in microscopic regions between hard γ‐rays over a wide range of distances of biological interest.

Conclusions: From a microdosimetric point of view, γ‐rays from ⁶⁰Co or ¹³⁷Cs are the most suitable reference radiations for specification of the relative biological effectiveness.     

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.     

Study on cell survival, induction of apoptosis and micronucleus formation in SCL-II cells after exposure to the auger electron emitter (99m)Tc

OBJECTIVE: To study the biological effectiveness of Auger electrons emitted by (99m)Tc on cell survival, induction of apoptosis and micronucleus (MN) formation in the human squamous cell carcinoma cell line SCL-II and compare the effects observed to those observed after exposure to external 60Co gamma radiation. MATERIAL AND METHODS: Cells were either gamma(60Co)-irradiated (0.67 Gy/min) or exposed to (99m)Tc-pertechnetate (0.95-14.3 MBq/ml) for 24 h under cell culture conditions and assayed for cell survival (colony-forming assay), micronucleus formation (cytochalasin B assay) and the frequency of apoptotic cells (fluorescence microscopy). Monte Carlo based dosimetry has been applied to derive the absorbed dose corresponding to the accumulated decays of (99m)Tc under the given geometry. RESULTS: Absorbed doses up to 0.5 Gy could be achieved after 99mTc-exposure leading to no substantial cell killing in this dose range except at one dose point (0.1 Gy) resulting in an relative biological effectiveness (RBE)SF 0.9 of 0.64 when compared to the 60Co reference radiation. MN formation was described best by a linear dose response and was consistently lower after 99mTc exposure when compared to 60Co irradiated cells resulting in an RBE of 0.37. Apoptosis induction was significantly increased after 99mTc exposure at much lower doses (0.1 Gy) when compared to the reference radiation. The (99m)Tc uptake experiments revealed an activity concentration ratio cells vs. medium of 0.07 after 24 h of exposure. CONCLUSION: No overall increased biological effectiveness due to the emitted Auger electrons of (99m)Tc, applied as sodium-pertechnetate, could be observed in the investigated cell line when compared to acute external gamma radiation. The RBEs in the range of 0.37-0.64 might be well explained by dose rate effects. The significantly increased apoptotic response after (99m)Tc-exposure at very low doses has to be further investigated.     

125I粒子持续低剂量率照射对人前列腺癌细胞的抑制作用

目的探讨^125I粒子持续低剂量率照射对人前列腺癌细胞株（PC3）增殖抑制以及对细胞周期的影响。方法^125I粒子（初始剂量率2.77cGy/h）和^60Coγ射线（吸收剂量率2.215Gy/min）对体外培养的PC3细胞进行0、0.5、1、1.5、2、4、6和8Gy照射,用细胞计数、锥虫蓝染色和集落形成法检测细胞增殖、细胞活力和细胞存活率的情况;用单击多靶模型拟合剂量存活曲线;用流式细胞仪检测细胞周期。结果随着照射剂量的增加,^125I粒子照射组的细胞生长比^60Coγ射线组更加明显地受到抑制（P〈0.05）。^125I粒子照射PC3细胞D0值为2.243,Dq为0.87,N为1.618,SF2为0.5。^60Co照射组PC3细胞放射生物学参数D0值为2.824,Dq为1.08,N为1.587,SF2为0.7。^60Co和125I粒子的RBE比值为1.4。与空白对照组相比,^125I粒子组和^60Co组4Gy照射细胞24h后均出现G2期阻滞。结论^125I粒子照射能抑制人前列腺癌细胞的增殖并能使PC3细胞阻滞于G2期。     

Influence of the sampling time on chromosomal aberrations at G2 phase in Syrian hamster embryonic cells irradiated with different types of radiation

PURPOSE: To investigate the time-course of chromosomal aberrations following radiations of differing LET. MATERIALS AND METHODS: Syrian hamster embryonic cells were irradiated with nitrogen ions (LET(infinity) = 530 keV/microm) and helium-ions (LET(infinity) = 36 and 77 keV/microm), also 137Cs gamma-rays as a reference radiation. The frequency of chromatid-type aberrations was determined after 0-6 h incubation in a 5% CO2 incubator at 37 degrees C. RESULTS: The amount of chromosomal damage per cell for nitrogen ions detected immediately after irradiation was lower than induced by 137Cs gamma-rays. In contrast, helium ions were more effective than gamma rays in inducing chromatid type damage. The RBE values for the nitrogen-ion beams were 0.45 for gaps, 0.43 for deletions and 0.20 for exchanges. For helium-ion beams, the RBE values for the 36 keV/microm beams and the 77 keV/microm beams were 1.2 and 1.5 for gaps, 1.3 and 2.1 for deletions, and 1.5 and 1.9 for exchanges, respectively. The frequency of cells with chromosomal damage following exposure to gamma-rays and helium-ion beams showed a downward trend with increasing incubation period. In contrast, in the case of nitrogen-ion beams, there was an increase with the incubation period. CONCLUSIONS: The results show that it is possible to underestimate chromosomal damage for different types of radiation by scoring aberrations at a single fixed sampling time.     

Potential of pottery materials in manufacturing radioactive waste containers.

Various pottery materials were evaluated for possible use in manufacturing containers for radioactive waste. Their potential was examined from the viewpoints of the effectiveness of disposal and the changes induced in them by gamma rays. Samples of these materials were irradiated with high-energy neutrons and gamma rays in a reactor near its core. the physical and mechanical properties of the materials before and after gamma irradiation (in a 60Co gamma cell) were compared. The study showed that pottery materials are resistant to radiation. Therefore, they were proposed for manufacturing drums for disposal of radioactive waste of high gamma activity.     

Heavy ion-induced chromosome breakage studied by premature chromosome condensation (PCC) in Syrian hamster embryo cells.

We have studied induction and repair of chromosome damage induced by high linear energy transfer (LET) heavy ions in G1/G0 interphase Syrian golden hamster embryo (SHE) cells as revealed by the premature chromosome condensation (PCC) technique. The number of chromosome breaks in condensed chromosomes induced by high LET heavy ions was higher than those induced by 137Cs gamma-rays. Compared with 137Cs gamma rays, the relative biological effectiveness (RBE) for PCC breaks was 1.5 for 35 keV/microns 4He ions, 1.9 for 77keV/microns 4He ions, and 2.5 for 530keV/microns 14N ions. Although 95% of the PCC breaks induced by gamma-rays rejoined during 8 h post-irradiation incubation, only 35-45% of fragments induced by high LET radiations rejoined in the same time. These results suggest that there is a difference, spatial or qualitative, in the initial chromosome damage produced by high LET radiations and low LET radiations.     

Cytotoxicity of 125I decay in the DNA double strand break repair deficient mutant cell line, xrs-5.

The survival of parental Chinese hamster ovary (CHO) K1 cells and the DNA double strand break (DSB) repair deficient mutant, xrs-5 was determined after accumulation of 125I decays. Both CHO and xrs-5 cells were extremely sensitive to accumulated 125I decays. The D0 values for CHO and xrs-5 cells were 40 and approximately 7 decays per cell, respectively. The difference in cell survival between CHO and xrs-5 cells was not due to differences in overall 125IUdR incorporation, differences in labelling index (LI) or differences in plating efficiency (PE). Relative biological effectiveness (RBE) values calculated relative to 137Cs gamma radiation survival values (D0 and D10) were higher in xrs-5 cells compared with CHO cells. Although both CHO and xrs-5 cells have high RBE values that correspond to a high sensitivity of CHO and xrs-5 cells to 125I decay. The higher RBE observed for xrs-5 cells in combination with the known repair defect in xrs-5 cells support the idea that unrepaired DNA double strand breaks are lethal to the cell.     

Effect of 50 kV roentgen rays and cobalt-60 gamma rays on the activity of ciliated cells

A method capable of continuously recording the changes in the physiologic activity of ciliated cells during irradiation has been used to analyse the importance of photon energy for the early biologic effects of ionizing radiation. Gamma rays from 60Co and 50 kV roentgen rays were used. Important differences were demonstrated and conventional RBE values are not valid for early effects. The results are discussed and RBE for 50 kV roentgen rays has been calculated in respect to early effects of irradiation.     

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.