Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice

Cutaneous leishmaniasis (CL) is a parasitic disease caused by the protozoan Leishmania spp. Pentavalent antimonial agents have been used as an effective therapy, despite their side effects and resistant cases. Their pharmacokinetics remain largely unexplored. This study aimed to investigate the pharmacokinetic profile of meglumine antimoniate in a murine model of cutaneous leishmaniasis using a radiotracer approach. Methods: Meglumine antimoniate was neutron-irradiated inside a nuclear reactor and was administered once intraperitoneally to uninfected and L. amazonensis-infected BALB/c mice. Different organs and tissues were collected and the total antimony was measured. Results: Higher antimony levels were found in infected than uninfected footpad (0.29% IA vs. 0.14% IA, p = 0.0057) and maintained the concentration. The animals accumulated and retained antimony in the liver, which cleared slowly. The kidney and intestinal uptake data support the hypothesis that antimony has two elimination pathways, first through renal excretion, followed by biliary excretion. Both processes demonstrated a biphasic elimination profile classified as fast and slow. In the blood, antimony followed a biexponential open model. Infected mice showed a lower maximum concentration (6.2% IA/mL vs. 11.8% IA/mL, p = 0.0001), a 2.5-fold smaller area under the curve, a 2.7-fold reduction in the mean residence time, and a 2.5-fold higher clearance rate when compared to the uninfected mice. Conclusions: neutron-irradiated meglumine antimoniate concentrates in infected footpad, while the infection affects antimony pharmacokinetics.(AU)

Production of a novel high strength heavy concrete using tourmaline and galena for neutron and photon radiation shielding

High density concrete is extensively used for efficient radiation attenuation in radiotherapy rooms and nuclear reactors. Over the past eight years, some efficient galena-based concrete samples for shielding X or gamma rays was produced. The goal of this study was to produce a novel high density concrete against neutron and photon radiations using tourmaline and galena. Attenuation of gamma photons was measured using a Farmer type ionization chamber with a standard [60]Co buildup cap on a Theratron[60] Co therapy unit. Neutron shielding characteristics were measured by using an Am-Be source. The MCNP4C radiation transport computer code was used to investigate the effects of various shield thicknesses on the attenuation of gamma-ray photons and neutrons. The concrete samples had a density of 4.0- 4.2 g/cm[3]. The compressive strength was 326 - 560 kg/cm2. The calculated value for Half Value Layer [HVL] of the tourmaline-galena concrete samples for 60Co gamma rays was 2.72 cm, which is much less than that of ordinary concrete [6.0 cm]. The MC-derived HVL for photons with the same energy was 2.77 cm, which is in a good agreement with the experimental data. Moreover, ToGa concrete had up to 10 times greater neutron attenuation compared to that of the reference concrete. Tourmalin-Galena Concrete opens a new horizon in economic and efficient gamma/neutron shielding in high-energy radiotherapy bunkers, nuclear power plants, and shielding of radioactive sources

The effect of photon energy on intensity-modulated radiation therapy (IMRT) plans for prostate cancer

PURPOSE: To evaluate the effect of common three photon energies (6-MV, 10-MV, and 15-MV) on intensity-modulated radiation therapy (IMRT) plans to treat prostate cancer patients. MATERIALS AND METHODS: Twenty patients with prostate cancer treated locally to 81.0 Gy were retrospectively studied. 6-MV, 10-MV, and 15-MV IMRT plans for each patient were generated using suitable planning objectives, dose constraints, and 8-field setting. The plans were analyzed in terms of dose-volume histogram for the target coverage, dose conformity, organs at risk (OAR) sparing, and normal tissue integral dose. RESULTS: Regardless of the energies chosen at the plans, the target coverage, conformity, and homogeneity of the plans were similar. However, there was a significant dose increase in rectal wall and femoral heads for 6-MV compared to those for 10-MV and 15-MV. The V20 Gy of rectal wall with 6-MV, 10-MV, and 15-MV were 95.6%, 88.4%, and 89.4% while the mean dose to femoral heads were 31.7, 25.9, and 26.3 Gy, respectively. Integral doses to the normal tissues in higher energy (10-MV and 15-MV) plans were reduced by about 7%. Overall, integral doses in mid and low dose regions in 6-MV plans were increased by up to 13%. CONCLUSION: In this study, 10-MV prostate IMRT plans showed better OAR sparing and less integral doses than the 6-MV. The biological and clinical significance of this finding remains to be determined afterward, considering neutron dose contribution.

Basics of particle therapy I: physics

With the advance of modern radiation therapy technique, radiation dose conformation and dose distribution have improved dramatically. However, the progress does not completely fulfill the goal of cancer treatment such as improved local control or survival. The discordances with the clinical results are from the biophysical nature of photon, which is the main source of radiation therapy in current field, with the lower linear energy transfer to the target. As part of a natural progression, there recently has been a resurgence of interest in particle therapy, specifically using heavy charged particles, because these kinds of radiations serve theoretical advantages in both biological and physical aspects. The Korean government is to set up a heavy charged particle facility in Korea Institute of Radiological & Medical Sciences. This review introduces some of the elementary physics of the various particles for the sake of Korean radiation oncologists' interest.

Monte Carlo characterization of photoneutrons in the radiation therapy with high energy photons: a comparison between simplified and full Monte Carlo models

The characteristics of secondary neutrons in a high energy radiation therapy room were studied using the MCNPX Monte Carlo [MC] code. Two MC models including a model with full description of head components and a simplified model used in previous studies were implemented for MC simulations. Results showed 4-53% difference between full and with the simplified model in the neutron fluence calculation. Additionally, in full MC model, increase in the field size decreased the neutron fluence but for simplified model, increase in the field size led to increase in neutron fluence. In calculating the neutron and capture gamma ray dose equivalent, simplified model overestimated [9-47%] and [20-61%] respectively in comparison to the full simulated model. However, a close agreement was seen between two models, for field size of 10x10 cm[2]. For MC modeling of photoneutrons and capture gamma in radiotherapy rooms, the detailed modeling of linac head instead of simplified model is recommended

Different Expressions of HIF-1alpha, Bcl-2 and Baxin DU145 Prostate Cancer Cells Transplanted in Nude Mouse between X-Ray and Neutron Irradiation / 대한방사선종양학회지

PURPOSE: To investigate the radiobiologic effects of neutron and X-ray irradiation on DU-145 prostate carcinoma cells by identifying the differences of HIF-1alpha expression and apoptosis. MATERIALS AND METHODS: Nude mice were injected with the human prostate cancer cell line, DU-145, and then irradiated with 2 Gy and 10 Gy X-rays, or 0.6 Gy and 3.3 Gy neutrons, respectively. The mice were sacrificed at 24 hours and 120 hours after irradiation. The expression levels of HIF-1alpha, Bcl-2 and Bax were compared with immunohistochemical staining and western blotting. The apoptotic indexes were compared with the Terminal deoxynucleotidyl biotin-dUTP nick and labeling (TUNEL) assay. RESULTS: At day 1, HIF-1alpha and Bcl-2 expression decreased, while Bax expression and the number of TUNEL positive cells increased in neutron irradiated groups for the control and X-ray irradiated groups. The Bcl-2/Bax ratio was significantly lower in the neutron irradiated groups regardless of dose (p=0.001). The same pattern of the differences in the expressions of the HIF-1alpha, Bcl-2, Bax, Bcl-2/Bax ratio, and apoptotic indexes were indentified at day 5. HIF-1alpha expression was related with Bcl-2 (p=0.031), Bax (p=0.037) expressions and the apoptotic indexes (p=0.016) at day 5. CONCLUSION: Neutron irradiation showed a decrease in HIF-1alpha, Bcl-2 expression, and Bcl-2/Bax ratio, but increased Bax expression regardless of dose. This study suggests that the differences radiobiological responses between photon and neutron irradiation may be related to different HIF-1alpha expression and subsequent apoptotic protein expressions.

Modification of 10 cGy neutron or gamma-rays induced chromosomal damages by hyperthermia: an in vitro study

To evaluate the effects of hyperthermia [HT] on the frequency of chromosomal aberrations induced by a low dose of neutron or gamma-rays in human peripheral blood lymphocytes. Blood samples were exposed to HT [41.5°C for 30 and 60min, 43°C for 15 and 30min], 10 cGy neutron or gamma-rays, HT + neutron/gamma, and neutron/gamma + HT. After standard cell culture, harvesting, fixation and staining, the chromosomal damages were scored in metaphase plates. HT alone at 41.5°C did not induce chromatid or chromosome aberrations, however, the frequency of damages was significantly higher at 43°C [P<0.05]. Furthermore, the chromosomal damages was significantly different when cells were irradiated with neutron or gamma-rays alone [P<0.01]. HT 1 hr post neutron/gamma irradiation significantly induced higher chromosome damages in comparison to HT 1 hr before irradiation [P<0.05]. The chromosomal damages were remarkably higher when cells were irradiated with neutron then heated at 43°C for 30 min. Since increasing frequency of chromosome damages increases probability of cell death, application of HT after neutron irradiation [instead of X-or gamma-rays] might be considered as a procedure for cells killing in radiotherapy

Transfer of moisture through the unsaturated zone in the tropical forest using the neutron probe

Knowledge of moisture content is crucial in assessing spatial and temporal movement of water through the unsaturated zone. Moisture storage is also important for monitoring the soil water balance and for validation of water balance models. The purpose of this work was to determine and analyse moisture content profiles at point locations in the unsaturated zone of a lateritic soil around Nsimi, south of Cameroon. Neutron probe has been connected to a set of tensiometers in an area of 60 ha. A comparative study between a site covered with vegetation and a site uncovered was conducted to assess the influence of vegetation in the process of moisture transfers. The results showed that the spatial distribution of moisture profiles varied according to the site and the texture of the soil, with in general increasing of moisture from the surface horizon toward the deeper layers. The mean values of moisture varied from theta m= 0,397 cm[3]/cm[3] on barren site, against theta m= 0,429 cm[3]/cm[3] in vegetation. Values of suction were generally strong in surface and at depth, but weak in the intermediate layers

Neutron KERMA factors of human tissues

A program to calculate the neutron KERMA in human tissues has been developed. The program was developed in Mathcad and contains the neutron kerma factors of those elements that are present in different human tissues. Having the elemental composition of any human tissue the neutron kerma can be easily calculated. The program was tested using the elemental composition of tumor tissues such as sarcoma, melanoma, carcinoma and adenoid cystic. Neutron kerma for adipose and muscle tissue for normal adult was calculated. The results are in agreement with those published in literature. The neutron kerma for water was also calculated because in some dosimetric calculations water is used to describe normal and tumor tissues. From this comparison was found that at larger energies kerma factors are approximately the same, but energies less than 100 eV the differences are large.

Campos neutrónicos producidos por un acelerador lineal para radioterapia / Neutron fields produced by linear accelerator for radiotherapy

Mediante una serie de medidas y cálculos Monte Carlo se han determinado las características dosimétricas y los espectros de los fotoneutrones que se producen en torno a un acelerador lineal para radioterapia de 18 MV. Las medidas se realizaron con dosímetros termoluminiscentes TLD 600 y TLD 700 que se expusieron desnudos y emparedados con Cd, así como dentro de una esfera de parafina y dentro de esferas Bonner.

Measurements and Monte Carlo calculations has been utilized to determine the dosimetric features as well as the neutron spectra of photoneutrons produced around an 18 MV linear accelerator for radiotherapy. Measurementes were carried out with bare and Cd covered thermolumiscent dosimeters, TLD600 and TLD700, as well as inside a paraffine moderator. TLD pairs were also utilized as thermal neutrons inside a Bonner sphere spectrometer.

Dosimetric Characteristics of a Thermal Neutron Beam Facility for Neutron Capture Therapy at HANARO Reactor / 의학물리

A thermal neutron beam facility utilizing a typical tangential beam port for Neutron Capture Therapy was installed at the HANARO, 30 MW multi-purpose research reactor. Mixed beams with different physical characteristics and relative biological effectiveness would be emitted from the BNCT irradiation facility, so a quantitative analysis of each component of the mixed beams should be performed to determine the accurate delivered dose. Thus, various techniques were applied including the use of activation foils, TLDs and ionization chambers. All the dose measurements were performed with the water phantom filled with distilled water. The results of the measurement were compared with MCNP4B calculation. The thermal neutron fluxes were 1.02E9 n/cm2 s and 6.07E8 n/cm2 s at 10 and 20 mm depth respectively, and the fast neutron dose rate was insignificant as 0.11 Gy/hr at 10 mm depth in water. The gamma-ray dose rate was 5.10 Gy/hr at 20 mm depth in water. Good agreement within 5%, has been obtained between the measured dose and the calculated dose using MCNP for neutron and gamma component and discrepancy with 14% for fast neutron flux. Considering the difficulty of neutron detection, the current study support the reliability of these results and confirmed the suitability of the thermal neutron beam as a dosimetric data for BNCT clinical trials.

Shielding studies on a total-body neutron activation facility

Prompt gamma neutron activation analysis [PGNAA] is known as a non-invasive technique capable of measuring elemental concentration in voluminous samples in a short period of time. Also it is a valuable diagnostic tool for total body elemental measurements. 252Cf and 241Am-Be sources which are usually used in this method, generate not only neutrons, but also emit high-energy and unwanted gamma-rays. Because the patient must be located against the neutron source, patient dose during an analysis is an important concern when using this technique. Gamma-rays were attenuated without losing the neutron flux or significant alteration in the neutron spectrum. A relatively safe body chemical composition analyzer was designed with an optimal spherical gamma-ray shield, enclosed to the neutron source. Effects of gamma-ray shielding and optimum radius of spherical Pb shield was investigated and compared with the unfiltered bare source, using MCNP4C code. Then, the gamma ray dose equivalent per source neutron rate [user defined parameter] in the soft tissue is calculated for different radiuses of spherical Pb shield, for both neutron sources. A decreasing flux of gamma-ray was observed when the radius of the spherical Pb shields increased. The value of this reduction was about 94% for 252Cf source when a lead spherical shield of radius 4 cm was used; while the reduction was about 50% for 241Am-Be source with the same spherical shield. For a spherical Pb shield of radius 4 cm, reduction of the gamma dose equivalent per source neutron rate was about 8.44_10-17 Sv when the neutron source was 252Cf and about 1.24_10-16 Sv when the neutron source was 241Am-Be. Results show using optimum gamma-ray shield geometry can reduce the patient absorbed dose per incident neutron in a body chemical composition analyzer

Evaluation of Biological Characteristics of Neutron Beam Generated from MC50 Cyclotron / 대한방사선종양학회지

PURPOSE: To evaluate biological characteristics of neutron beam generated by MC50 cyclotron located in the Korea Institute of Radiological and Medical Sciences (KIRAMS). MATERIALS AND METHODS: The neutron beams generated with 15 mm Beryllium target hit by 35 MeV proton beam was used and dosimetry data was measured before in-vitro study. We irradiated 0, 1, 2, 3, 4 and 5 Gy of neutron beam to EMT-6 cell line and surviving fraction (SF) was measured. The SF curve was also examined at the same dose when applying lead shielding to avoid gamma ray component. In the X-ray experiment, SF curve was obtained after irradiation of 0, 2, 5, 10, and 15 Gy. RESULTS: The neutron beams have 84% of neutron and 16% of gamma component at the depth of 2 cm with the field size of 26 x 26 cm2, beam current 20 micro A, and dose rate of 9.25 cGy/min. The SF curve from X-ray, when fitted to linear-quadratic (LQ) model, had 0.611 as alpha/beta ratio (alpha=0.0204, beta=0.0334, R2=0.999, respectively). The SF curve from neutron beam had shoulders at low dose area and fitted well to LQ model with the value of R2 exceeding 0.99 in all experiments. The mean value of alpha and beta were -0.315 (range, -0.254 ~ -0.360) and 0.247 (0.220~0.262), respectively. The addition of lead shielding resulted in no straightening of SF curve and shoulders in low dose area still existed. The RBE of neutron beam was in range of 2.07~2.19 with SF=0.1 and 2.21~2.35 with SF=0.01, respectively. CONCLUSION: The neutron beam from MC50 cyclotron has significant amount of gamma component and this may have contributed to form the shoulder of survival curve. The RBE of neutron beam generated by MC50 was about 2.2.

Histopathological changes of testes and eyes by neutron irradiation with boron compounds in mice

This study was performed to investigate the biological effects of boron neutron capture therapy (BNCT) on the testes and eyes in mice using HANARO Nuclear Reactor, Korea Atomic Energy Research Institute. BNCT relies on the high capacity of (10)B in capturing thermal neutrons. Sodium borocaptate (BSH, 75 ppm, iv) and boronophenylalanine (BPA, 750 ppm, ip) have been used as the boron delivery agents. Mice were irradiated with neutron (flux: 1.036739E +09, Fluence 9.600200E+12) by lying flat pose for 30 (10 Gy) or 100 min (33 Gy) with or without boron carrier treatment. In 45 days of irradiation, histopathological changes of the testes and eyes were examined. Thirty-three Gy neutron irradiation for 100 min induced testicular atrophy in which some of seminiferous tubules showed complete depletion of spermatogenic germ cells. Lens epithelial cells and lens fiber were swollen and showed granular changes in an exposure time dependent manner. However, boron carrier treatment had no significant effect on the lesions. These results suggest that the examination of histopathological changes of lens and testis can be used as "biological dosimeters" for gauging radiation responses and the HANARO Nuclear Reactor has sufficient capacities for the BNCT.

Neutron Generation from a 24 MV Medical Linac / 의학물리

The energy spectra and dose calculations were performed for secondary neutrons from a 24 MV LINAC using MCNPX code (V2, 4, 0). The energy spectra for neutrons and photons emitted from the LINAC head, and absorbed dose to water were calculated in water phantom. The absorbed doses calculated with Monte Carlo were 0.66~0.35 mGy/photon Gy at the surface to d=5 cm, and calculated with interaction data was 0.52 mGy/photon Gy at the depth of electron equilibrium in water. We have shown that this work can be applied to dose estimation of neutrons from high energy LINAC through the comparison of our results with other results.

Dosimetry of the Low Fluence Fast Neutron Beams for Boron Neutron Capture Therapy / 대한방사선종양학회지

PURPOSE: For the research of Boron Neutron Capture Therapy (BNCT), fast neutrons generated from the MC-50 cyclotron with maximum energy of 34.4 MeV in Korea Cancer Center Hospital were moderated by 70 cm paraffin and then the dose characteristics were investigated. Using these results, we hope to establish the protocol about dose measurement of epi-thermal neutron, to make a basis of dose characteristic of epi-thermal neutron emitted from nuclear reactor, and to find feasibility about accelerator-based BNCT. METHOD AND MATERIALS: For measuring the absorbed dose and dose distribution of fast neutron beams, we used Unidos 10005 (PTW, Germany) electrometer and IC-17 (Far West, USA), IC-18, EIC-1 ion chambers manufactured by A-150 plastic and used IC-17M ion chamber manufactured by magnesium for gamma dose. There chambers were flushed with tissue equivalent gas and argon gas and then the flow rate was 5 cc per minute. Using Monte Carlo N-Particle (MCNP) code, transport program in mixed field with neutron, photon, electron, two dimensional dose and energy fluence distribution was calculated and there results were compared with measured results. RESULTS: The absorbed dose of fast neutron beams was 6.47x10-3 cGy per 1 MU at the 4 cm depth of the water phantom, which is assumed to be effective depth for BNCT. The magnitude of gamma contamination intermingled with fast neutron beams was 65.2+/-0.9% at the same depth. In the dose distribution according to the depth of water, the neutron dose decreased linearly and the gamma dose decreased exponentially as the depth was deepened. The factor expressed energy level, D20/D10, of the total dose was 0.718. CONCLUSION: Through the direct measurement using the two ion chambers, which is made different wall materials, and computer calculation of isodose distribution using MCNP simulation method, we have found the dose characteristics of low fluence fast neutron beams. If the power supply and the target material, which generate high voltage and current, will be developed and gamma contamination was reduced by lead or bismuth, we think, it may be possible to accelerator-based BNCT.

Considerações sobre a terapia de captura de nêutrons pelo Boro / Considerations on Boron neutron capture therapy

Este artigo descreve a técnica de radioterapia chamada Boron Neutron Capture Therapy (BNCT), isto é, Terapia de Captura de Nêutrons por Boro. Serão abordados conceitos básicos em BNCT, em particular como esta técnica tem sido usada na tentativa de combater glioblastoma multiforme. Uma breve revisão histórica dos estudos clínicos feitos nas décadas de 50 e 60 será apresentada, incluindo resultados recentes do Laboratório Nacional de Brookhaven - BNL e do Instituto Tecnológico de Massachusetts - MIT. A experiência japonesa na área será comentada. Atualmente, novas ensaios clínicos no MIT e BNL foram iniciados, tentando obter a cura para o glioblastoma multiforme e melanoma intracranial periférico. Dados radiobiológicos e protocolos clínicos usados na Fase I do MIT serão apresentados. Considerações de como BNCT poderá ser aplicado no Brasil serão traçadas. O artigo aponta para a possibilidade de utilização da braquiterapia via Cf-252 acoplada à técnica de terapia de captura de nêutrons – NCT como uma alternativa simples e barata de implementação de BNCT no país.

The Combined Effect of Fast Neutron and hyperthermia according to the Sequence and Interval in MKN-45 Cells / 대한방사선종양학회지

PURPOSE: It has been well established that response of cells and tissues to low LET radiations(X- or grmma-ray) can enhanced by comdining with hyperthermia. However, There has been relatively little of hyperthermia on the possible modification of either cellular or tissue responses to other types of radiation. So, We investigated the combined effect of fast neutron irradiation and hyperthermia according to the sequence and time interval of the two MATERIALS AND METHODS: In MKN-45 cells, a human stomach cancer cell line, Surviving fractions were measured according to the sequence treatment of 6,4,2,0 hour interval for fast neutron irradiation(1.5Gy) combined with hyperthermia(41 degrees C for 30 min or 43 degrees C for 30 min). RESULTS: D(0) and n of MKN-45 for neutron were 0.8Gy and 2.5, respectively. The surviving fraction by 1.5 Gy of neutron was 0.36+/-0.34. Interacting powers were mostly. The surviving fraction by 1.5 Gy of neutron was 0.36+/-0.34. Interacting powers were mostly ranged between 1 and 2, bur they were 3.0Gy 2.7, respectively for hyperthermia (41 degrees C for 30 min) followed by neutron irradiation 6 and 4 hours later. CONCLUSION: The combined effect of fast neutron (1.5Gy) and hyperthermia (41 degrees C or 43 degrees C for 30min) is largely independently additive. Preceding mild hyperthermia (41 degrees C for 30 min) 4 or 6 hours before neutron may cause decreased sensitivity to subsequent neutron irradiation.

Production of Re-188 / 대한핵의학회잡지

188Re (beta=22 MeV; gamma=155 keV; T1/2=16.9 hours) is an attractive therapeutic radioisotope which is produced from decay of reactor-produced tungsten-188 parent (T1/2=69 days). 188W has been produced from the double neutron capture reaction of 186W. 188Re can be easily obtained by elution of saline on alumina based 186W/188Re generator, which is commercially available. Complexes labelled with 188Re have been developed for the radiotherapy treatment of diseases because of the desirable nuclear properties of the radioisotope and it's chemical properties similar to those of technetium, a well established diagnostic agent.

Study on proliferation in vitro and mineral composition of Phyllathus amarus by combined activated neutron analysis

The conservation of precious source of medicinal herb from traditional medicine phyllathus amarus (= P. niruri L.) was effectively conducted by in vitro propagation. The process of in vitro propagation of this culture consists of main following stages: (1) Start budding: suitable materials are meristems, apical buds and auxiliary buds; Rapid propagation: The medium for highest propagation coefficient is MS; creating complete plantlets: rapid root differentiation with good quality roots is observed in the medium MS+ NAA; in nurseries: the suitable substrate for ex-vitro stage is black sandy soils; (2) The medium able to form potassium at highest rate is MS + 2.4D; (3) The analysis of mineral compositions shows low contents of heavy metals and rare earth elements (REE), but considerably high in potassium, that may be due to diuretic activity of P. amarus.