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PubMed2006

Photon and fast neutron dosimetry using aluminium oxide thermoluminescence dosemeters.

Al(2)O(3):Mg,Y thermoluminescence (TL) dosemeters were used to measure photon and fast neutron doses in a fast neutron beam recently implemented at the Portuguese Research Reactor, Nuclear and Technological Institute, Portugal. The activation of Al(2)O(3):Mg,Y by fast neutrons provides information about the fast neutron component by measuring the activity of the reaction products and the self-induced TL signal. Additionally, the first TL reading after irradiation determines the photon dose. The elemental composition of the dosemeters was determined by instrumental neutron activation analysis and by particle induced X-ray emission. Results demonstrate that Al(2)O(3):Mg,Y is an adequate material to discriminate photon and fast neutron fields for reactor dosimetry purposes.

Aluminum Oxide↗
PubMed2004

Alanine and TLD coupled detectors for fast neutron dose measurements in neutron capture therapy (NCT).

A method was investigated to measure gamma and fast neutron doses in phantoms exposed to an epithermal neutron beam designed for neutron capture therapy (NCT). The gamma dose component was measured by TLD-300 [CaF2:Tm] and the fast neutron dose, mainly due to elastic scattering with hydrogen nuclei, was measured by alanine dosemeters [CH3CH(NH2)COOH]. The gamma and fast neutron doses deposited in alanine dosemeters are very near to those released in tissue, because of the alanine tissue equivalence. Couples of TLD-300 and alanine dosemeters were irradiated in phantoms positioned in the epithermal column of the Tapiro reactor (ENEA-Casaccia RC). The dosemeter response depends on the linear energy transfer (LET) of radiation, hence the precision and reliability of the fast neutron dose values obtained with the proposed method have been investigated. Results showed that the combination of alanine and TLD detectors is a promising method to separate gamma dose and fast neutron dose in NCT.

Alanine↗
PubMed1992

Cytogenetic effect of 235U neutrons and d(50)+Be fast neutrons.

Induction of chromosome aberrations in G0 lymphocytes of peripheral human blood exposed to 235U and d(50)+Be neutron radiation was studied. Dose--effect relationships for different types of chromosome aberrations were analyzed. Linear dependence of the effect was established for the studied neutron radiation, except for the yield of dicentrics exposed to d(50)+Be neutrons. Accordingly to the yield of dicentrics, the relative biological efficiency (RBE) of 235U and d(50)+Be neutrons was 19.5 and 4.14, respectively.

Beryllium↗
PubMed1996

Comparative study of DNA radiolysis by fast neutrons and gamma-rays.

The effect of fast neutrons on cells is different from that of gamma-rays: the relative (to gamma) biological effect (RBE) is higher than one and the oxygen enhancement ratio (OER) is lower than that of gamma-rays. We searched for differences between the effects of the two radiations on DNA, the critical target of radiations. Using a model plasmid DNA we observed that for the same absorbed dose, fast neutrons induce twice fewer single strand breaks (SSB) and 1.5 more double strand breaks (DSB) than gamma-rays. A transition metal ion, the Cu++, is a better sensitizer of DNA breakage with fast neutrons than with gamma-rays. In anoxia, cysteamine, a positively charged thiol, is a better radioprotector against neutrons than against gamma-rays. In presence of cysteamine, the OER is lower for neutrons than for gamma-rays. These results are discussed in terms of different physical properties of the two types of radiation.

Copper↗
PubMedDate not supplied

Fast neutron radiotherapy: for equal or for better?

The renewed application of fast neutrons in clinical radiotherapy has been stimulated by fundamental radiobiological findings. The biological effects of high LET radiation, including fast neutrons, are different from those obtained with x rays in at least three respects: the oxygen enhancement ratio, the sensitivity of cells at different phases of the cell cycle, and the contribution of sublethal damage to cell reproductive death. Furthermore, wide variations in relative biological effectiveness (RBE) have been observed for different tumors and normal tissues. Measurements of volume changes in human pulmonary metastases indicate that the RBE for slowly growing tumors which are generally well-differentiated is higher than that for poorly differentiated lesions. Six thousand patients have now been treated with fast neutron beams. The results of the clinical applications vary according to the method of application and to the type of cancer involved: treatment of inoperable malignancies of the salivary gland is very encouraging: the therapeutic gain is rather small for bladder and rectal cancers, soft tissue sarcomas and advanced carcinomas of the cervix; the responses of brain tumors are very disappointing. Most neutron radiotherapy applications have been less than optimal because of inadequate physical and technical conditions. Despite these difficulties, some interesting clinical data have become available. Due to the technical shortcomings, the possible advantages of fast neutrons are probably underestimated for many tumor sites. Well-designed clinical trials, preferably performed with high energy cyclotrons in clinical environments, will provide a decisive answer to the question of the usefulness of the new radiation modality.

Brain Neoplasms↗
PubMed1984

[Does fast-neutron radiotherapy merely reduce the radiation dosage?].

We examined whether fast-neutron radiotherapy is superior to low-LET radiotherapy by comparing the relationship between cell survival and tumor control probabilities after exposure of tumor-bearing (species) to the two modalities. Analysis based on TCD50 assay and lung colony assay indicated that single dose of fast neutron achieved animal cures at higher survival rates than other radiation modalities including single and fractionated gamma-ray doses, fractionated doses of fast neutron, and the mixed-beam scheme with a sequence of N-gamma-gamma-gamma-N. We conclude that fast-neutron radiotherapy cured animal tumors with lower cell killing rates other radiation modalities.

Animals↗
PubMed1992

Accelerated fast neutron therapy: a pilot study.

The clinical role of fast neutron therapy has been limited by excessive late normal tissue damage. A pilot study of accelerated fractionation of fast neutron therapy was performed, based on the rationale that this should result in an increase in the response in acute reacting tissues (normal and malignant), with no change in late damage and a consequent increase in the therapeutic ratio. Further accelerated fractionation should improve the local control of rapidly proliferating tumour, without the potential problem of inadequate reoxygenation inherent in accelerated photon schedules. 6 or 12 fractions of 62 MeV (p-Be) neutrons were given over 12 days to 27 sites in 23 patients with locally advanced tumours. With a dose reduction of 12% (18 Gy), acceptable skin and oral mucosa early reactions were obtained. A larger dose reduction (15%) was required at pelvic sites. The incidence of late EORTC/RTOG grade 4 toxicity was 46%. The overall response rate was 76% with a complete response rate of 16%. For locally advanced breast cancer, the complete response rate was 9%, which compares unfavourably with previous results with conventional neutron fractionation schedules. The combination of a low overall complete response rate and excessive late normal tissue toxicity suggests that accelerated fractionation of fast neutrons does not lead to an improvement in the therapeutic ratio, and that late normal tissue damage will continue to be dose limiting.

Adult↗
PubMed1991

Basic radiobiological investigations of fast neutrons.

The radiobiological properties of a cyclotron-produced 43-MeV (p----Be) fast-neutron beam relative to gamma rays have been investigated using Chinese hamster V79 cells in culture. As expected, the relative biological effectiveness (RBE) of this neutron beam for cell killing was shown to increase as dose decreased, and the effectiveness per unit dose was slightly less compared to a 25-MeV (d----Be) neutron beam. By tracing single cells that formed microcolonies after irradiation, we found cell proliferation kinetics to be retarded to a greater extent by fast neutrons than by gamma irradiation. Following either neutron or gamma irradiation, a fraction of the irradiated cells failed to divide in the first postirradiation division and another fraction could produce as many as four generations of progeny before proliferation stopped. The properties of these cells presumed to be destined for death suggest that more than one mechanism and/or multistep process underlies the radiation-induced proliferative death. The fast-neutron beam was also found to be more effective quantitatively than gamma rays in producing DNA double-strand breaks (DSBs, measured by nondenaturing filter elution), and G1-phase chromosome fragments (measured by the premature chromosome condensation technique). However, the reverse was observed for DNA single-strand breaks (SSBs, measured by alkaline filter elution or hydroxylapatite uncoiling). Interestingly, both fast neutrons and gamma rays produced a large component of SSBs and DSBs with a fast-rejoining time constant of about 2-5 min, which appears to be independent of dose. The latter results could not resolve the possibility of lengthening the repair-time constant by increasing radiation dose within the range that is reflected by the shoulder of the survival curve, and consequently did not support the idea of repair saturation as a mechanism for the presence of the shoulder. The RBE for the hypoxanthine phosphoribosyl transferase mutation frequency per survivor at the 10% survival level was estimated to be 2.5, a value that is comparable to the RBE (2.1) for cell killing at the same survival level. Although most of the above-mentioned findings are compatible qualitatively with the relatively high-LET (linear energy transfer) nature associated with the fast-neutron beam, the significance of the action attributable to the mixture of LET could not be delineated in these experiments. Further, the biological significance of DSBs and chromosome aberration and the molecular mechanisms responsible for the repair and expression of these damaging processes remain to be elucidated.

Animals↗
PubMed2000

Accelerator mass spectrometry of 63Ni at the Munich Tandem Laboratory for estimating fast neutron fluences from the Hiroshima atomic bomb.

After the release of the present dosimetry system DS86 in 1987, measurements have shown that DS86 may substantially underestimate thermal neutron fluences at large distances (>1,000 m) from the hypocenter in Hiroshima. This discrepancy casts doubts on the DS86 neutron source term and, consequently, the survivors' estimated neutron doses. However, the doses were caused mainly by fast neutrons. To determine retrospectively fast neutron fluences in Hiroshima, the reaction 63Cu(n, p)63Ni can be used, if adequate copper samples can be found. Measuring 63Ni (half life 100 y) in Hiroshima samples requires a very sensitive technique, such as accelerator mass spectrometry (AMS), because of the relatively small amounts of 63Ni expected (approximately 10(5)-10(6) atoms per gram of copper). Experiments performed at Lawrence Livermore National Laboratory have demonstrated in 1996 that AMS can be used to measure 63Ni in Hiroshima copper samples. Subsequently, a collaboration was established with the Technical University of Munich in view of its potential to perform more sensitive measurements of 63Ni than the Livermore facility and in the interest of interlaboratory validation. This paper presents the progress made at the Munich facility in the measurement of 63Ni by AMS. The Munich accelerator mass spectrometry facility is a combination of a high energy tandem accelerator and a detection system featuring a gas-filled magnet. It is designed for high sensitivity measurements of long-lived radioisotopes. Optimization of the ion source setup has further improved the sensitivity for 63Ni by reducing the background level of the 63Cu isobar interference by about two orders of magnitude. Current background levels correspond to a ratio of 63Ni/Ni<2x10(-14) and suggest that, with adequate copper samples, the assessment of fast neutron fluences in Hiroshima and Nagasaki is possible for ground distances of up to 1500 m, and--under favorable conditions--even beyond. To demonstrate this capability, we have measured successfully 6Ni/Ni ratios as low as (3.5 +/- 0.6) x 10(-13). The latter are, based on DS86, representative of a ratio expected from a typical Hiroshima copper sample at about 1,300-m ground range.

Body Burden↗
PubMed1994

Enhancement of fast neutron beams with boron neutron capture therapy. A mechanism for achieving a selective, concomitant tumor boost.

Both fast neutron radiotherapy and boron neutron capture therapy (BNCT) have been utilized to treat malignant disease. Herein we discuss the potential of combining these treatments to enhance the effectiveness of fast neutron therapy through a concomitant BNCT boost. Using a fast neutron beam generated from a 50 MeV proton on beryllium reaction, we have determined that 0.1% of the beam per microgram of boron-10 per gram of tissue (microgram/g) can be deposited via BNCT. Our mathematical modeling predicts that BNCT enhancement of our beam will lead to an additional 1-2 logs of tumor cell kill for boron-10 concentrations of 30-50 micrograms/g. We have validated this via V-79 cell line in vitro measurements. A Poisson model estimation of how this additional cell kill will influence local tumor control, predicts that BNCT enhancement of fast neutron radiation will lead to a clinically significant improvement in outcome.

Animals↗
PubMed1991

The role of fast neutrons in radiooncology--a critical appraisal.

The contribution of fast neutrons to local tumour control has been investigated worldwide since the mid-60's in more than 20 institutions. The high expectations anticipated from the promising results of experimental studies could not be adequately realized in the clinic. The late normal tissue damage was unacceptable due to poor depth dose characteristics and further technical limitations of the first generation low-energy machines. Even with sophisticated therapy planning systems and high-energy cyclotrons as well as comparable late normal tissue damage as witnessed after photons, only a few tumour entities have responded superiorly to fast neutrons. These particularly include macroscopic tumours of the salivary glands, prostate and, potentially, soft and osseous tissues. The role of fast neutrons for head and neck cancer has not yet been definitely proved. For bladder-, cervical- and rectal carcinomas, non-small cell lung-, pancreatic- and breast cancers as well as malignant gliomas, no therapeutic benefit as compared with photons was observed in the case of macroscopic residual or inoperable recurrent tumours.

Aged↗
PubMed1994

Ultrastructural changes in the cochlea of the guinea pig after fast neutron irradiation.

Guinea pigs were irradiated with fast neutrons. After a single dose of 2, 6, 10, or 15 Gy was applied, scanning and transmission electron microscopy of the temporal bone was performed to assess the effect of fast neutron irradiation on the cochlea. Outer hair cell damage appeared with neutron irradiation of more than 10 Gy, and inner hair cell damage with neutron irradiation of more than 15 Gy. Outer hair cells were more severely damaged than inner hair cells. No statistically significant differences were found in damage of basal, middle, and apical turns. The second and third rows of outer hair cells were more severely damaged than the first row of outer hair cells. The most significant findings in transmission electron microscopy were clumping of chromatin and extension of the heterochromatin in the nuclei of hair cells. The cytoplasmic changes were sequestration of cytoplasm, various changes of mitochondria, formation of vacuoles, and irregularly arranged stereocilia. The morphologic change in stria vascularis was intercellular and perivascular fluid accumulation. It appeared to be a reversible process.

Animals↗
PubMed1992

Morphologic effects of fast neutrons or photons on the canine kidney.

Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness of fast neutrons on normal pulmonary tissue. The right anterior abdomen, including the cranial half of the right kidney, was included in the field of irradiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250, or 3375 cGy in four fractions per week for 6 weeks. Fifteen dogs received 3000, 4500, or 6750 cGy of photons (five/group) in an identical fractionation pattern. All 12 neutron irradiated dogs receiving 3375 and 2250 cGy and 1 of 6 receiving 1500 cGy, developed clinical and clinical pathologic signs of hepatic, pancreatic, and gastrointestinal disturbances, but no signs of renal injury were seen. These 13 dogs died or were euthanatized 47-367 days after irradiation. Only 1 of 5 dogs receiving 6750 cGy of photons developed similar signs and died 708 days post-irradiation. The remaining 11 neutron irradiated dogs and 14 photon irradiated dogs eventually died of other causes. All 39 dogs were necropsied and their kidneys were compared to each other and to control dogs. Radiation induced lesions included hemorrhages, necrosis and disappearance of tubular epithelia, glomerulosclerosis, atrophy and fibrosis. These lesions were associated with degenerative and occlusive vascular changes and were much more severe in the neutron irradiated dogs. The relative biologic effectiveness of fast neutrons for canine kidney assessed by gross and microscopic pathology is approximately 4.5 (6750/1500).

Animals↗
PubMed1988

[Fast neutron therapy in the National Institute of Radiological Sciences; 10 years' experience and future study].

A total number of 1623 patients were treated with fast neutrons produced by bombarding a thick Beryllium target with 30 MeV deuterons between November 1975 and December 1987. The results of clinical trials with fast neutrons have shown that carcinoma of the salivary gland and the prostate and Pancoast tumor of the lung were indications for fast neutron therapy, and that the patients suffering from osteosarcoma, malignant melanoma and soft tissue sarcoma had indications for fast neutrons when fast neutrons were combined with surgery. Neither carcinoma of the pancreas nor glioblastoma multiforme had indications because of complications of normal tissues. High LET radiation therapy will be evaluated by using heavy ions characterized by Bragg peak combined with biological effects.

Adult↗
PubMed2003

Validation of a pencil beam model-based treatment planning system for fast neutron therapy.

Treatment planning systems (TPSs) are used to compute dose delivered to the patient. In the case of fast neutron therapy, TPSs are mostly not of general purpose but are dedicated to one facility. This is due to the few fast neutron facilities worldwide and due to the high variation in the neutron energy distributions. Efforts have been undertaken to develop a new TPS that could be applied to all the existing fast neutron facilities. The University Hospital of Essen operates a d (14 MeV) + Be fast neutron beam and the TPS used is based on an empirical model. In a previous study, the empirical model has been evolved to a pencil beam model of 35 monoenergetic neutron beams. Monte Carlo techniques have been utilized to compute distributions of the energy deposition due to primary and scattered neutrons in a simple geometry water phantom. The experimental validation of the method is now presented. Depth dose curves in water of monoenergetic neutrons have been derived from the distributions of energy deposition. The resultant depth dose curves have been utilized in order to determine the depth dose curves of the fast neutron beam of the Essen facility for the 14 radiation field sizes available in this facility. This determination requires the initial neutron spectrum. As this spectrum could not be measured at the Essen facility, the initial neutron spectrum of the Physikalisch Technische Bundesanstalt, Braunschweig, Germany, which operates the same cyclotron, was used. The calculated depth dose curves were compared to experimental depth dose curves that have been obtained in water at the University Hospital of Essen. The comparison between calculated and experimental depth dose curves showed significant deviations in the case of large radiation fields and of depth less than 5 cm. In the case of radiation field areas less than 150 cm2 and depth more than 5 cm (usual clinical situation), the measured and calculated values are in a good agreement. In the case of clinical situation, the dependence on the radiation field size is relatively well taken into account by the model presented here.

Computer Simulation↗
PubMed1989

Fast neutron radiotherapy for sarcomas of soft tissue, bone, and cartilage.

The basic radiobiological rationale for the use of fast neutron radiotherapy in the treatment of classically radioresistant tumors such as soft tissue sarcomas, osteogenic sarcomas, and chondrosarcomas is reviewed. There are no definitive randomized studies comparing high and low linear energy transfer radiotherapy for these tumor systems, but a review of published series is highly suggestive of a therapeutic advantage for fast neutrons. For soft tissue sarcomas, the local control rate is 53% (158 of 297) with fast neutrons, compared with 38% (49 of 128) with photons/electrons; for osteogenic sarcomas, the local control rate is 55% (40 of 73) with fast neutrons, compared with 21% (15 of 73) with photons/electrons; and for chondrosarcomas, the local control rate is 49% (25 of 51) with fast neutrons, compared with 33% (10 of 30) with photons/electrons. An ongoing clinical trial for these tumors is also described.

Bone Neoplasms↗