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PubMed2004

Fast-neutron OSL sensitivity of thallium-doped ammonium salts.

The main problem in selecting suitable thermoluminescent (TL) materials for fast-neutron dosimetry is finding a material that is both tissue-equivalent and not damaged upon heating. Optically stimulated luminescence (OSL) avoids the need to heat the materials and allows the use of materials with a high content of hydrogen (responsible for 90% of the absorbed dose of fast-neutrons). The choice of studying the ammonium salts for their OSL properties was based on the calculation of their neutron kerma factor. A constant ratio of an ammonium salt's kerma coefficients to the tissue's kerma coefficients (in the fast-neutron range) is a prerequisite for a similar energy response to neutrons, i.e. tissue equivalency. The salts studied are NH4Br and (NH4)2SiF6 both doped with Tl+. This paper describes the OSL properties of Tl(+)-doped NH4Br and (NH4)2SiF6 after exposure to 14.5 MeV neutrons to explore their potential for developing new, tissue-equivalent OSL materials suitable for fast-neutron dosimetry. The relative neutron sensitivity, k, defined as the ratio of the sensitivity of the material to neutrons to its sensitivity to gamma rays, has been determined for 14.5 MeV neutrons and varies between k = 0.15 and k = 0.5. The latter value is a factor 2.5 higher than that found for known TL materials (k < or = 0.2). A drawback of these materials is the fast fading of the OSL signal.

Body Burden↗
PubMed1990

Fast neutron therapy at the end of 1988--a survey of the clinical data.

The clinical results reported from the different neutron therapy centres, in USA, Europe and Asia, are reviewed. Fast neutrons were proven to be superior to photons for locally extended inoperable salivary gland tumours. The reported overall local control rates are 67% and 24% respectively. Paranasal sinuses and some tumours of the head and neck area, especially extended tumours with large fixed lymph nodes, are also indications for neutrons. By contrast, the results obtained for brain tumours were, in general, disappointing. Neutrons were shown to bring a benefit in the treatment of well differentiated slowly growing soft tissue sarcomas. The reported overall local control rates are 53% and 38% after neutron and photon irradiation respectively. Better results were also reported for bone- and chondrosarcomas. The reported local control rates are 54% for osteosarcomas and 49% for chondrosarcomas after neutron irradiation; the corresponding values are 21% and 33% respectively after photon irradiation. For locally extended prostatic adenocarcinoma, the superiority of mixed schedule (neutrons + photons) was demonstrated by a RTOG randomized trial (local control rates 77% for mixed schedule compared to 31% for photons). Neutrons were also shown to be useful for palliative treatment of melanomas. Further studies are needed in order to evaluate the benefit of fast neutrons for other localisations such as cervix, bladder, rectum. It can be concluded that fast neutrons are superior to photons for at least 10% of the radiotherapy patients. It is likely that the new high- energy hospital-based cyclotrons will further extend the indications of neutron therapy. However, patient selection remains one of the main problems and there is a need for development of individual predictive tests.

Adenocarcinoma↗
PubMed2001

Fast neutron radiotherapy for soft tissue and cartilaginous sarcomas at high risk for local recurrence.

PURPOSE: The practice policy at the University of Washington has been to employ fast neutron radiotherapy for soft tissue sarcoma lesions with prognostic features predictive for poor local control. These include gross residual disease/inoperable disease, recurrent disease, and contaminated surgical margins. Cartilaginous sarcomas have also been included in this high-risk group. This report updates and expands our previously described experience with this approach. METHODS AND MATERIALS: Eighty-nine soft tissue sarcoma lesions in 72 patients were treated with neutron radiotherapy in our department between 1984 and 1996. Six patients, each with solitary lesions, were excluded from analysis due to lack of follow-up. Seventy-three percent were treated with fast neutron radiation alone, the rest with a combination of neutrons and photons. Median neutron dose was 18.3 nGy (range 4.8-22). Forty-two patients with solitary lesions were treated with curative intent. Thirty-one patients (including 7 previously treated with neutrons) with 41 lesions were treated with the goal of local palliation. Tumors were predominantly located in the extremity and torso. Thirty of 35 (85%) of curative group patients treated postoperatively had close or positive surgical margins. Thirty-four (82%) lesions treated for palliation were unresectable. Thirty-five patients (53%) were treated at the time of recurrence. Median tumor size at initial presentation was 8.0 cm (range 0.6-29), median treated gross disease size was 5.0 cm (range 1-22), and 46/69 evaluable lesions (67%) were judged to be of intermediate to high histologic grade. Fourteen patients (21%) had chondrosarcomas. RESULTS: Median follow-up was 6 months (range 2-47) and 38 months (range 2-175) for the palliative and curative groups, respectively. Kaplan-Meier estimates were obtained for probability of local relapse-free survival (68%), distant disease-free survival (59%), cause-specific survival (68%), and overall survival (66%) at 4 years for the curatively treated group. For the palliatively treated group, estimated local relapse-free survival at 1 year was 62%. Log-rank analysis of the curative group revealed recurrent disease to be the only risk factor predictive for significantly worse local and distant disease-free survival. Intermediate-/high-grade histology was predictive for inferior overall survival. Effective clinical response was documented for 21/27 (78%) lesions treated palliatively. Ten patients (15%) experienced serious chronic radiation-related complications. All of these patients had clinical situations requiring delivery of high neutron doses and/or large radiotherapy fields. CONCLUSION: Fast neutron radiotherapy is locally effective for soft tissue and cartilaginous sarcomas having well-recognized high-risk features. Results in the palliative setting appear to be particularly encouraging, with neutrons frequently providing significant symptomatic response for gross disease, with minimal serious chronic sequelae. Fast neutron radiotherapy should be considered in patients at high risk for local recurrence in both the curative and palliative settings.

Adult↗
PubMed1998

A morphometric analysis of glomerular and tubular alterations following fast-neutron irradiation of the pig and monkey kidney.

PURPOSE: The morphologic responses of the pig and monkey kidney to fractionated fast-neutron irradiation were assessed. METHODS AND MATERIALS: The right kidney of approximately 14-week-old female Large White pigs was irradiated with 6.6-12.2 Gy of fast neutrons (42 MeVd-->Be) given as 12 fractions over 18 days; the left kidney served as the contralateral unirradiated kidney. Both kidneys were removed at necropsy 2 years postirradiation. In addition, the remaining hypertrophied kidney of four unilaterally nephrectomized adult rhesus monkeys was irradiated with a total dose of 11.0 Gy fast neutrons (45 MeVp-->Be) given in an identical fractionation regimen to that used in the pig studies. These kidneys were removed when the animals exhibited renal failure, between 32-94 weeks postirradiation. Glomeruli were assessed for the presence of pathologic features, including intercapillary eosinophilic material (ICE), ectatic capillaries, thrombi, hemorrhage, and sclerosis. The relative proportion of renal cortex occupied by glomeruli, interstitium, normal, or abnormal tubules was determined using a Chalkley point grid. RESULTS: The incidence of normal glomeruli, ectatic capillaries, thrombosis, and periglomerular fibrosis were significantly different in the irradiated pig kidneys compared with the unirradiated contralateral kidneys (p < or = 0.02). Linear regression analysis demonstrated a significant dose relationship in terms of normal glomeruli, ectatic capillaries, and ICE (r > or = 0.64; p < or = 0.04). Irradiation was also associated with a significant (p < 0.0001) decrease and increase in the volume of renal cortex occupied by normal and abnormal tubules, respectively. Similar morphometric changes were noted in the irradiated monkey kidneys. CONCLUSIONS: The morphologic changes seen in the pig and monkey kidney after fractionated irradiation with fast neutrons are similar to those previously noted after single-dose or fractionated-photon irradiation. These findings support the hypothesis that the development of radiation nephropathy in these various models involves common pathophysiological mechanisms.

Animals↗
PubMed1981

The pathologic effects of fractionated fast neutrons or photons on canine liver.

Thirty-nine adult male purebred beagles received either fast neutron or photon irradiation to the right thorax to determine the effects on pulmonary tissue. The right half of the liver was included in the field of radiation. Twenty-four dogs (six/group) received fast neutrons with a mean energy of 15 MeV to total doses of 1000, 1500, 2250, or 3375 rads in four fractions per week for 6 weeks. Fifteen dogs received 3000, 4500, or 6750 total rads of photons (five dogs/group) in an identical fractionation pattern. All neutron-irradiated dogs receiving 3375 and 2250 rads and one receiving 1500 rads developed clinical signs, hepatic enzyme, and bilirubin elevations, and the dogs died or were euthanized in extremis on postirradiation day 47-291. Signs of liver injury, other than enzyme changes, have not developed to date (1200-1300 days) in the remaining dogs, except in one 6750-rad photon dog that died of hepatic failure on postirradiation day 708. At necropsy, the irradiated right lobes of the liver were atrophic and the nonirradiated left lobes underwent compensatory hypertrophy. Hepatic arterioles and bile ducts were injured in every dog, but no obstructive lesions were observed in hepatic veins. Portal fibroplasia, bile retention, and proliferation of bile ductules was common; the latter two changes also occurred in the nonirradiated lobes. No qualitative differences were observed between hepatic lesions in neutron- versus photon-irradiated dogs. The relative biological effectiveness of fast neutrons for liver damage appears to be no less than 4.5.

Animals↗
PubMed2006

Measurements of fast neutrons in Hiroshima by use of (39)Ar.

The survivors of the A-bomb explosions over Hiroshima and Nagasaki were exposed to a mixed neutron and gamma radiation field. To validate the high-energy portion of the neutron field and thus the neutron dose to the survivors, a method is described that allows retrospective assessment of the fast neutrons from the A-bombs. This is accomplished by the extraction of the noble gas argon from biotites separated from Hiroshima granite samples, and then the detection of the (39)Ar activity that was produced by the capture of the fast neutrons on potassium. Adjusted to the year 1945, activities measured in the first samples taken at distances of 94, 818, 992, and 1,173 m from the hypocenter were 6.9+/-0.2, 0.32+/-0.01, 0.14+/-0.02, and 0.09+/-0.01 mBq/g K, respectively. All signals were significantly above detector background and show low uncertainties. Considering their uncertainties they agree with the calculated (39)Ar activation in the samples, based on the most recent dosimetry system DS02. It is concluded that this method can be used to investigate samples obtained from large distances in Hiroshima, where previous data on fast neutrons are characterized by considerable uncertainties. Additionally, the method can be used to reconstruct the fast neutron fluence in Nagasaki, where no experimental data exist.

Argon↗
PubMed2004

Dose- and time-dependent responses for micronucleus induction by X-rays and fast neutrons in gill cells of medaka (Oryzias latipes).

Medaka fish (Oryzias latipes) were exposed to various doses of X-rays or fast neutrons, and the frequency of micronucleated cells (MNCs) was measured in gills sampled at 12- or 24-hr intervals from 12 to 96 hr after exposure. The resulting time course of MNC frequency was biphasic, with a clear peak 24 hr after exposure, irrespective of the kind of radiation applied and the dose used. The half-life of MNCs induced in the gill tissues by the two exposures fluctuated around 28 hr, with no significant dose-dependent trend for either X-ray- or neutron-exposed fish. As assayed 24 hr after exposure, the MNC frequency increased linearly over the control level with increasing doses of both X-rays and fast neutrons. The relative biological effectiveness (RBE) of fast neutrons to X-rays for MNC induction was estimated to be 4.3 +/- 0.6. This value is close to the RBE value of 5.1 +/- 0.3 reported for fast neutron induction of somatic crossing-over mutations in Drosophila melanogaster that arise from recombination repair of DNA double-strand breaks. These results and other data support our conclusion that the medaka gill cell micronucleus assay is a reliable short-term test for detecting potential inducers of DNA double-strand breaks.

Animals↗
PubMed1986

Prospects for the application of fast neutrons in cancer therapy. Radiobiological bases and survey of the clinical data.

The rationale for introducing fast neutrons in therapy initially was a reduction in the Oxygen Enhancement Ratio (OER). The recent radiobiological developments indicate that, more generally, fast neutrons tend to reduce the difference in radiosensitivity between cell lines, or related to the degree of oxygenation (Oxygen Gain Factor), the position of the cells in the mitotic cycle (Kinetics Gain Factor), etc. The reduction of the differences in radiosensitivity brings a benefit for certain types of tumours (normally resistant to photons), but a disadvantage for other types of tumours (those which can currently be controlled by photon treatment). A review of the available clinical data is presented. The tumour types or sites for which a benefit has been observed are discussed: locally advanced tumours of the salivary glands, paranasal sinuses, some tumours of the head and neck area with metastatic lymph nodes, slowly growing, well differentiated soft tissue sarcomas, inoperable/recurrent melanomas, locally extended (C, D1) prostatic adenocarcinomas. Selection of the patients suitable for neutron therapy remains the main problem. Collaboration between neutron therapy centres is essential to accelerate the acquisition of sufficient clinical data needed in order to improve patient selection, as well as the optimum modality of application of fast neutrons.

Energy Transfer↗
PubMedDate not supplied

An introduction to fast neutron therapy for the radiation therapy technologist.

Clinical research into fast neutron radiation therapy has shown a renewed interest with the advent of the new generation cyclotrons presently being built and already on line in various parts of the country. These units will have neutron beams with better depth dose properties and uniform treatment policy for all facilities. This should ensure that adequate clinical studies are carried out that will define the role of fast neutron radiotherapy in the treatment of cancer.

Fast Neutrons↗
PubMed2005

A cargo inspection system based on pulsed fast neutron analysis (PFNA).

A cargo inspection system based on pulsed fast neutron analysis (PFNA) is to be used at a border crossing to detect explosives and contraband hidden in trucks and cargo containers. Neutrons are produced by the interaction of deuterons in a deuterium target mounted on a moveable scan arm. The collimated pulsed fast neutron beam is used to determine the location and composition of objects in a cargo container. The neutrons produce secondary gamma rays that are characteristic of the object's elemental composition. The cargo inspection system building consists of an accelerator room and an inspection tunnel. The accelerator room is shielded and houses the injector, accelerator and the neutron production gas target. The inspection tunnel is partially shielded. The truck or container to be inspected will be moved through the inspection tunnel by a conveyor system. The facility and radiation source terms considered in the shielding design are described.

Computer-Aided Design↗
PubMedDate not supplied

[Biological effectiveness of fast neutrons with a mean energy of 22 MeV].

Biological effectiveness of fast neutrons of a mean energy of 22 MeV obtained by the reaction d[50 MeV]----Be, measured by the death rate, was substantially lower than that of division spectrum neutrons of a mean energy of 1.2 MeV. LD50/30 of the division spectrum neutrons was within 2.57 +/- 0.07 Gy and that of 22 MeV fast neutrons 4.79 +/- 0.13 Gy. The RBE coefficient for the studied neutrons was 1.34 +/- 0.05 as estimated by LD50/30 and 1.5 +/- 0.1 as determined by D37 for a cell model of radiation affection.

Animals↗
PubMed1992

Preimplantation growth delay and micronucleus formation after in vivo exposure of mouse zygotes to fast neutrons.

Mouse zygotes were irradiated with fast neutrons (0.06 to 1.00 Gy) 1 h after conception and examined at various intervals (24 to 100 h after conception) for embryonic development and micronucleus formation. The frequency of micronuclei per cell increased linearly with dose in 2-cell embryos observed at 24 h after conception and in 4-cell and 8-cell embryos at 48 h after conception. Compared with X rays, the relative biological effectiveness of neutrons for the induction of micronuclei per embryo was 2.5 at 24 h after conception and 3.5 at 48 h after conception. Neutron-induced micronucleus formation was accompanied by morphological growth delay and a significant decrease in the number of cells in the embryos. An inverse relationship was found between the number of cells in embryos and the number of micronuclei when observed at 48 h after conception following irradiation with 0.12 to 1.00 Gy and at 78 h after conception following exposure to 0.50 Gy. The effect of neutron irradiation on embryonic development was likely to be mediated by cell death, as suggested by a significantly increased dead cell index in blastocysts following irradiation of zygotes.

Animals↗
PubMedDate not supplied

Fast neutrons from a 25-MeV betatron.

Since published results for the fast-neutron dose per x-ray rad from high-energy therapy installations have differed by as much as a factor of 300, we have measured the neutron production from our 25-MeV betatron. Fast-neutron activation of aluminum foils was the method used. The effect of photoneutron production in the detectors, which has affected some past work, has been eliminated. A major source of neutrons in the treatment field was the platinum target. The neutron spectra used in the calculations of fluence were obtained by interpolation between published energies and between neighboring elements. Fluences per rad of x rays without a phantom were largely independent of field size and energy in the range 18-23 MeV. At 100 cm SSD and 23 MeV a large beam flattener contributed 15% of the neutrons, the remainder coming equally from the target and background. A phantom increased the neutron fluence/rad of x rays by 0%-10% depending on the field size. At 23 MeV we estimated the neutron dose to a patient to be 2.2 X 10(-4) rad per rad of x rays inside the treatment field and 3 X 10(-5) at 20 cm outside the field. The uncertainty in these figures is believed to be +/- 50%. In the electron beam the neutron dose per rad was about 50 times smaller than in the x-ray beam. Estimates were made of neutron fluences at other energies and target thicknesses. We discuss our results in comparison with those of others.

Fast Neutrons↗
PubMed1996

Fast neutron radiotherapy and boron neutron capture therapy: application to a human melanoma test system.

Fast neutron radiotherapy has proven to be an effective form of treatment in a selected subset of tumors (salivary gland tumors, sarcomas, and locally-advanced prostate cancer), but has not proven to be more beneficial than conventional photon irradiation for the majority of tumor types upon which it has been tested. Normal tissue tolerance limits preclude simply further escalating the neutron dose. Boron neutron capture (BNC) provides a way of selectively augmenting the radiation dose to the tumor. This process is described, and cell culture and animal model data reviewed. An irradiation configuration was developed where an enhancement of 2.10(-3) for 1 microgram of 10B per gram of tissue was achieved. This is similar to the enhancement achievable in the center of a 20 x 20 cm field envisioned for future applications such as metastases in the brain. A boron concentration of 50 micrograms per gram of tumor tissue leads to a 10% increase in the delivered physical dose in this scenario. The first human test of BNC enhancement of a fast neutron radiotherapy beam using pharmacologically-acceptable doses of orally-administered, 10B-enriched, L-paraboronophenylalanine is reported. An enhancement of tumor response was demonstrated for a melanoma skin nodule test system. Boron levels achieved in blood, skin, and tumors are presented. Future research plans are discussed.

Administration, Oral↗
PubMed1977

Radioresistance of mongolian gerbils. Fast neutrons.

Seventy-six 8 week old Mongolian gerbils were exposed to acute, whole-body fast neutrons produced by The University of Michigan 83-in. cyclotron. Groups of seven or eigth gerbils were given doses between 485 and 881 rad at 25 rad per minute. The LD 50/30 determined by probit analysis was 750 rad, with 95 per cent fiducial limits of 733 and 776. For the 50 per cent mortality level, an r.b.e. of fast neutrons compared with cobalt-60 of 1-45 was determined. For the same end-point, the r.b.e. for fast neutrons compared with X-rays is 1-33. Mortality data, body-weight and microhaematocrit changes are discussed.

Animals↗
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↗
PubMed1996

The application of a multirod collimator in fast neutron therapy.

The application of a novel multirod collimator in fast neutron therapy to produce irregularly shaped fields with partial transmission and fully blocked areas is discussed. The transmission through the tungsten rods is measured in free space in broad beam geometry. A model based on scatter analysis is applied in calculating the thickness of the rods required to produce partially blocked areas. The effect of a full beam block is also measured. Measurements have been made in a water phantom to confirm the computational model. The good agreement between the measured and calculated values demonstrates that the scatter model can be safely applied to fast neutron beam dose computations.

Cyclotrons↗
PubMed1978

The use of 10B to enhance the tumour dose in fast-neutron therapy.

Incorporation of 10B in tumours treated by fast-neutron therapy would increase the tumour dose via the reaction 10B(n, alpha)7Li which occurs with partially thermalised neutrons. The extent of the dose enhancement was measured for neutron beams with median energies of 2.4, 3.3, 7.0 and 9.0 MeV by two techniques: with a BF3 proportional counter in three beams and activation of 23Na in the fourth. The results obtained with the two techniques are in good agreement. The magnitude of the dose enhancement depends upon the depth, field size and neutron beam energy. The dose enhancement at a depth of 8 cm varied from 0.32% with the lowest-energy beam to 0.07% with the highest-energy beam for each microgram of 10B uptake per gram of tissue. The products of the reaction in 10B would, however, have an RBE about twice that of the fast-neutron dose in the absence of boron. The method may be useful if drugs providing adequate uptake of 10B can be synthesised.

Beryllium↗