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Sample records for capture therapy field

  1. Neutron field for boron neutron capture therapy

    SciTech Connect

    Kanda, K.; Kobayashi, T.

    1986-01-01

    Recently, the development of an epithermal neutron source has been required by medical doctors for deeper neutron penetrations, which is to be used for deep tumor treatment and diagnosis of metastasis. Several attempts have already been made to realize an epithermal neutron field, such as the undermoderated neutron beam, the filtered neutron beam, and the use of a fission plate. At present, these facilities can not be used for actual therapy. For the treatment of deep tumor, another method has been also proposed in normal water in the body is replaced by heavy water to attain a deeper neutron penetration. At Kyoto University's Research Reactor Institute, almost all physics problems have been settled relative to thermal neutron capture therapy that has been used for treating brain tumors and for biological experiments on malignant melanoma. Very recently feasibility studies to use heavy water have been started both theoretically and experimentally. The calculation shows the deeper penetration of neutrons as expected. Two kinds of experiments were done by using the KUR guide tube: 1. Thermal neutron penetration measurement. 2. Heavy water uptake in vitro sample. In addition to the above experiment using heavy water, the development of a new epithermal neutron source using a large fission plate is in progress, which is part of a mockup experiment of an atomic bomb field newly estimated.

  2. Thermal neutron irradiation field design for boron neutron capture therapy of human explanted liver.

    PubMed

    Bortolussi, S; Altieri, S

    2007-12-01

    The selective uptake of boron by tumors compared to that by healthy tissue makes boron neutron capture therapy (BNCT) an extremely advantageous technique for the treatment of tumors that affect a whole vital organ. An example is represented by colon adenocarcinoma metastases invading the liver, often resulting in a fatal outcome, even if surgical resection of the primary tumor is successful. BNCT can be performed by irradiating the explanted organ in a suitable neutron field. In the thermal column of the Triga Mark II reactor at Pavia University, a facility was created for this purpose and used for the irradiation of explanted human livers. The neutron field distribution inside the organ was studied both experimentally and by means of the Monte Carlo N-particle transport code (MCNP). The liver was modeled as a spherical segment in MCNP and a hepatic-equivalent solution was used as an experimental phantom. In the as-built facility, the ratio between maximum and minimum flux values inside the phantom ((phi(max)/phi(min)) was 3.8; this value can be lowered to 2.3 by rotating the liver during the irradiation. In this study, the authors proposed a new facility configuration to achieve a uniform thermal neutron flux distribution in the liver. They showed that a phi(max)/phi(min) ratio of 1.4 could be obtained without the need for organ rotation. Flux distributions and dose volume histograms were reported for different graphite configurations.

  3. Neutron capture therapies

    SciTech Connect

    Yanch, Jacquelyn C.; Shefer, Ruth E.; Klinkowstein, Robert E.

    1999-01-01

    In one embodiment there is provided an application of the .sup.10 B(n,.alpha.).sup.7 Li nuclear reaction or other neutron capture reactions for the treatment of rheumatoid arthritis. This application, called Boron Neutron Capture Synovectomy (BNCS), requires substantially altered demands on neutron beam design than for instance treatment of deep seated tumors. Considerations for neutron beam design for the treatment of arthritic joints via BNCS are provided for, and comparisons with the design requirements for Boron Neutron Capture Therapy (BNCT) of tumors are made. In addition, exemplary moderator/reflector assemblies are provided which produce intense, high-quality neutron beams based on (p,n) accelerator-based reactions. In another embodiment there is provided the use of deuteron-based charged particle reactions to be used as sources for epithermal or thermal neutron beams for neutron capture therapies. Many d,n reactions (e.g. using deuterium, tritium or beryllium targets) are very prolific at relatively low deuteron energies.

  4. Neutron capture therapies

    SciTech Connect

    Yanch, J.C.; Shefer, R.E.; Klinkowstein, R.E.

    1999-11-02

    In one embodiment there is provided an application of the {sup 10}B(n,{alpha}){sup 7}Li nuclear reaction or other neutron capture reactions for the treatment of rheumatoid arthritis. This application, called Boron Neutron Capture Synovectomy (BNCS), requires substantially altered demands on neutron beam design than for instance treatment of deep seated tumors. Considerations for neutron beam design for the treatment of arthritic joints via BNCS are provided for, and comparisons with the design requirements for Boron Neutron Capture Therapy (BNCT) of tumors are made. In addition, exemplary moderator/reflector assemblies are provided which produce intense, high-quality neutron beams based on (p,n) accelerator-based reactions. In another embodiment there is provided the use of deuteron-based charged particle reactions to be used as sources for epithermal or thermal neutron beams for neutron capture therapies. Many d,n reactions (e.g. using deuterium, tritium or beryllium targets) are very prolific at relatively low deuteron energies.

  5. Iodine neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Ahmed, Kazi Fariduddin

    A new technique, Iodine Neutron Capture Therapy (INCT) is proposed to treat hyperthyroidism in people. Present thyroid therapies, surgical removal and 131I treatment, result in hypothyroidism and, for 131I, involve protracted treatment times and excessive whole-body radiation doses. The new technique involves using a low energy neutron beam to convert a fraction of the natural iodine stored in the thyroid to radioactive 128I, which has a 24-minute half-life and decays by emitting 2.12-MeV beta particles. The beta particles are absorbed in and damage some thyroid tissue cells and consequently reduce the production and release of thyroid hormones to the blood stream. Treatment times and whole-body radiation doses are thus reduced substantially. This dissertation addresses the first of the several steps needed to obtain medical profession acceptance and regulatory approval to implement this therapy. As with other such programs, initial feasibility is established by performing experiments on suitable small mammals. Laboratory rats were used and their thyroids were exposed to the beta particles coming from small encapsulated amounts of 128I. Masses of 89.0 mg reagent-grade elemental iodine crystals have been activated in the ISU AGN-201 reactor to provide 0.033 mBq of 128I. This activity delivers 0.2 Gy to the thyroid gland of 300-g male rats having fresh thyroid tissue masses of ˜20 mg. Larger iodine masses are used to provide greater doses. The activated iodine is encapsulated to form a thin (0.16 cm 2/mg) patch that is then applied directly to the surgically exposed thyroid of an anesthetized rat. Direct neutron irradiation of a rat's thyroid was not possible due to its small size. Direct in-vivo exposure of the thyroid of the rat to the emitted radiation from 128I is allowed to continue for 2.5 hours (6 half-lives). Pre- and post-exposure blood samples are taken to quantify thyroid hormone levels. The serum T4 concentration is measured by radioimmunoassay at

  6. Application of an ultraminiature thermal neutron monitor for irradiation field study of accelerator-based neutron capture therapy.

    PubMed

    Ishikawa, Masayori; Tanaka, Kenichi; Endo, Satrou; Hoshi, Masaharu

    2015-03-01

    Phantom experiments to evaluate thermal neutron flux distribution were performed using the Scintillator with Optical Fiber (SOF) detector, which was developed as a thermal neutron monitor during boron neutron capture therapy (BNCT) irradiation. Compared with the gold wire activation method and Monte Carlo N-particle (MCNP) calculations, it was confirmed that the SOF detector is capable of measuring thermal neutron flux as low as 10(5) n/cm(2)/s with sufficient accuracy. The SOF detector will be useful for phantom experiments with BNCT neutron fields from low-current accelerator-based neutron sources.

  7. Application of an ultraminiature thermal neutron monitor for irradiation field study of accelerator-based neutron capture therapy

    PubMed Central

    Ishikawa, Masayori; Tanaka, Kenichi; Endo, Satrou; Hoshi, Masaharu

    2015-01-01

    Phantom experiments to evaluate thermal neutron flux distribution were performed using the Scintillator with Optical Fiber (SOF) detector, which was developed as a thermal neutron monitor during boron neutron capture therapy (BNCT) irradiation. Compared with the gold wire activation method and Monte Carlo N-particle (MCNP) calculations, it was confirmed that the SOF detector is capable of measuring thermal neutron flux as low as 105 n/cm2/s with sufficient accuracy. The SOF detector will be useful for phantom experiments with BNCT neutron fields from low-current accelerator-based neutron sources. PMID:25589504

  8. Capture and Transport of Laser Accelerated Protons by Pulsed Magnetic Fields: Advancements Toward Laser-Based Proton Therapy

    NASA Astrophysics Data System (ADS)

    Burris-Mog, Trevor J.

    The interaction of intense laser light (I > 10 18 W/cm2) with a thin target foil leads to the Target Normal Sheath Acceleration mechanism (TNSA). TNSA is responsible for the generation of high current, ultra-low emittance proton beams, which may allow for the development of a compact and cost effective proton therapy system for the treatment of cancer. Before this application can be realized, control is needed over the large divergence and the 100% kinetic energy spread that are characteristic of TNSA proton beams. The work presented here demonstrates control over the divergence and energy spread using strong magnetic fields generated by a pulse power solenoid. The solenoidal field results in a parallel proton beam with a kinetic energy spread DeltaE/E = 10%. Assuming that next generation lasers will be able to operate at 10 Hz, the 10% spread in the kinetic energy along with the 23% capture efficiency of the solenoid yield enough protons per laser pulse to, for the first time, consider applications in Radiation Oncology. Current lasers can generate proton beams with kinetic energies up to 67.5 MeV, but for therapy applications, the proton kinetic energy must reach 250 MeV. Since the maximum kinetic energy Emax of the proton scales with laser light intensity as Emax ∝ I0.5, next generation lasers may very well accelerate 250 MeV protons. As the kinetic energy of the protons is increased, the magnetic field strength of the solenoid will need to increase. The scaling of the magnetic field B with the kinetic energy of the protons follows B ∝ E1/2. Therefor, the field strength of the solenoid presented in this work will need to be increased by a factor of 2.4 in order to accommodate 250 MeV protons. This scaling factor seems reasonable, even with present technology. This work not only demonstrates control over beam divergence and energy spread, it also allows for us to now perform feasibility studies to further research what a laser-based proton therapy system

  9. Development and characteristics of the HANARO neutron irradiation facility for applications in the boron neutron capture therapy field.

    PubMed

    Kim, Myong-Seop; Lee, Byung-Chul; Hwang, Sung-Yul; Kim, Heonil; Jun, Byung-Jin

    2007-05-07

    The HANARO neutron irradiation facility for various applications in the boron neutron capture therapy (BNCT) field was developed, and its characteristics were investigated. In order to obtain the sufficient thermal neutron flux with a low level of contamination by fast neutrons and gamma rays, a radiation filtering method was adopted. The radiation filter was designed by using a silicon single crystal, cooled by liquid nitrogen, and a bismuth crystal. The installation of the main components of the irradiation facility and the irradiation room was finished. Neutron beam characteristics were measured by using bare and cadmium-covered gold foils and wires. The in-phantom neutron flux distribution was measured for flux mapping inside the phantom. The gamma-ray dose was determined by using TLD-700 thermoluminescence dosimeters. The thermal and fast neutron fluxes and the gamma-ray dose were calculated by using the MCNP code, and they were compared with experimental data. The thermal neutron flux and Cd ratio available at this facility were confirmed to be 1.49 x 10(9) n cm(-2) s(-1) and 152, respectively. The maximum neutron flux inside the phantom was measured to be 2.79 x 10(9) n cm(-2) s(-1) at a depth of 3 mm in the phantom. The two-dimensional in-phantom neutron flux distribution was determined, and significant neutron irradiation was observed within 20 mm from the phantom surface. The gamma-ray dose rate for the free beam condition was expected to be about 80 cGy h(-1). These experimental results were reasonably well supported by calculation using the facility design code. This HANARO thermal neutron facility can be used not only for clinical trials, but also for various pre-clinical studies in the BNCT field.

  10. Measurements of neutron distribution in neutrons-gamma-rays mixed field using imaging plate for neutron capture therapy.

    PubMed

    Tanaka, Kenichi; Endo, Satoru; Hoshi, Masaharu

    2010-01-01

    The imaging plate (IP) technique is tried to be used as a handy method to measure the spatial neutron distribution via the (157)Gd(n,gamma)(158)Gd reaction for neutron capture therapy (NCT). For this purpose, IP is set in a water phantom and irradiated in a mixed field of neutrons and gamma-rays. The Hiroshima University Radiobiological Research Accelerator is utilized for this experiment. The neutrons are moderated with 20-cm-thick D(2)O to obtain suitable neutron field for NCT. The signal for IP doped with Gd as a neutron-response enhancer is subtracted with its contribution by gamma-rays, which was estimated using IP without Gd. The gamma-ray response of Gd-doped IP to non-Gd IP is set at 1.34, the value measured for (60)Co gamma-rays, in estimating the gamma-ray contribution to Gd-doped IP signal. Then measured distribution of the (157)Gd(n,gamma)(158)Gd reaction rate agrees within 10% with the calculated value based on the method that has already been validated for its reproducibility of Au activation. However, the evaluated distribution of the (157)Gd(n,gamma)(158)Gd reaction rate is so sensitive to gamma-ray energy, e.g. the discrepancy of the (157)Gd(n,gamma)(158)Gd reaction rate between measurement and calculation becomes 30% for the photon energy change from 33keV to 1.253MeV.

  11. Neutron capture therapy for melanoma

    SciTech Connect

    Coderre, J.A.; Glass, J.D.; Micca, P.; Fairchild, R.G.

    1988-01-01

    The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs.

  12. Workshop on neutron capture therapy

    SciTech Connect

    Fairchild, R.G.; Bond, V.P.

    1986-01-01

    Potentially optimal conditions for Neutron Capture Therapy (NCT) may soon be in hand due to the anticipated development of band-pass filtered beams relatively free of fast neutron contaminations, and of broadly applicable biomolecules for boron transport such as porphyrins and monoclonal antibodies. Consequently, a number of groups in the US are now devoting their efforts to exploring NCT for clinical application. The purpose of this Workshop was to bring these groups together to exchange views on significant problems of mutual interest, and to assure a unified and effective approach to the solutions. Several areas of preclinical investigation were deemed to be necessary before it would be possible to initiate clinical studies. As neither the monomer nor the dimer of sulfhydryl boron hydride is unequivocally preferable at this time, studies on both compounds should be continued until one is proven superior.

  13. Approach to magnetic neutron capture therapy

    SciTech Connect

    Kuznetsov, Anatoly A. . E-mail: spod@sky.chph.ras.ru; Podoynitsyn, Sergey N.; Filippov, Victor I.; Komissarova, Lubov Kh.; Kuznetsov, Oleg A.

    2005-11-01

    Purpose: The method of magnetic neutron capture therapy can be described as a combination of two methods: magnetic localization of drugs using magnetically targeted carriers and neutron capture therapy itself. Methods and Materials: In this work, we produced and tested two types of particles for such therapy. Composite ultradispersed ferro-carbon (Fe-C) and iron-boron (Fe-B) particles were formed from vapors of respective materials. Results: Two-component ultradispersed particles, containing Fe and C, were tested as magnetic adsorbent of L-boronophenylalanine and borax and were shown that borax sorption could be effective for creation of high concentration of boron atoms in the area of tumor. Kinetics of boron release into the physiologic solution demonstrate that ultradispersed Fe-B (10%) could be applied for an effective magnetic neutron capture therapy. Conclusion: Both types of the particles have high magnetization and magnetic homogeneity, allow to form stable magnetic suspensions, and have low toxicity.

  14. Porphyrins for boron neutron capture therapy

    DOEpatents

    Miura, Michiko; Gabel, Detlef

    1990-01-01

    Novel compounds for treatment of brain tumors in Boron Neutron Capture Therapy are disclosed. A method for preparing the compounds as well as pharmaceutical compositions containing said compounds are also disclosed. The compounds are water soluble, non-toxic and non-labile boronated porphyrins which show significant uptake and retention in tumors.

  15. Dose prescription in boron neutron capture therapy

    SciTech Connect

    Gupta, N.M.S.; Gahbauer, R.A. ); Blue, T.E. ); Wambersie, A. )

    1994-03-30

    The purpose of this paper is to address some aspects of the many considerations that need to go into a dose prescription in boron neutron capture therapy (BNCT) for brain tumors; and to describe some methods to incorporate knowledge from animal studies and other experiments into the process of dose prescription. Previously, an algorithm to estimate the normal tissue tolerance to mixed high and low linear energy transfer radiations in BNCT was proposed. The authors have developed mathematical formulations and computational methods to represent this algorithm. Generalized models to fit the central axis dose rate components for an epithermal neutron field were also developed. These formulations and beam fitting models were programmed into spreadsheets to simulate two treatment techniques which are expected to be used in BNCT: a two-field bilateral scheme and a single-field treatment scheme. Parameters in these spreadsheets can be varied to represent the fractionation scheme used, the [sup 10]B microdistribution in normal tissue, and the ratio of [sup 10]B in tumor to normal tissue. Most of these factors have to be determined for a given neutron field and [sup 10]B compound combination from large animal studies. The spreadsheets have been programmed to integrate all of the treatment-related information and calculate the location along the central axis where the normal tissue tolerance is exceeded first. This information is then used to compute the maximum treatment time allowable and the maximum tumor dose that may be delivered for a given BNCT treatment. The effect of different treatment variables on the treatment time and tumor dose has been shown to be very significant. It has also been shown that the location of D[sub max] shifts significantly, depending on some of the treatment variables-mainly the fractionation scheme used. These results further emphasize the fact that dose prescription in BNCT is very complicated and nonintuitive. 11 refs., 6 figs., 3 tabs.

  16. Proceedings of the first international symposium on neutron capture therapy

    SciTech Connect

    Fairchild, R.G.; Brownell, G.L.

    1982-01-01

    This meeting was arranged jointly by MIT and BNL in order to illuminate progress in the synthesis and targeting of boron compounds and to evaluate and document progress in radiobiological and dosimetric aspects of neutron capture therapy. It is hoped that this meeting will facilitate transfer of information between groups working in these fields, and encourage synergistic collaboration.

  17. Boron thermal/epithermal neutron capture therapy

    SciTech Connect

    Fairchild, R.G.

    1982-01-01

    The development of various particle beams for radiotherapy represents an attempt to improve dose distribution, and to provide high LET radiations which are less sensitive to ambient physical and radiobiological factors such as oxygen tension, cell cycle, and dose rate. In general, a compromise is necessary as effective RBE is reduced in order to spread the dose distribution over the anticipated tumor volume. The approach of delivering stable non-toxic isotopes to tumor, and then activating these atoms subsequently via an external radiation beam has mator advantages; problems associated with high uptake of these isotopes in competing cell pools are obviated, and the general tumor volume can be included in the treatment field of the activating beam. As long as the normal tissues supporting tumor show a low uptake of the isotope to be activated, and as long as the range of the reaction products is short, dose will be restricted to tumor, with a consequent high therapeutic ratio. Neutron Capture Therapy (NCT) is generally carried out by activating boron-10 with low energy neutrons. The range of the high LET, low OER particles from the /sup 10/B(n, ..cap alpha..)/sup 7/Li reaction is approx. 10..mu.., or one cell diameter, a situation that is optimal for cell killing. Significant advantages may be gained by using the NCT procedure in conjunction with improved tissue penetration provided with epithermal or filtered beams, and new compounds showing physiological binding to tumor.

  18. Visual Field Asymmetry in Attentional Capture

    ERIC Educational Resources Information Center

    Du, Feng; Abrams, Richard A.

    2010-01-01

    The present study examined the spatial distribution of involuntary attentional capture over the two visual hemi-fields. A new experiment, and an analysis of three previous experiments showed that distractors in the left visual field that matched a sought-for target in color produced a much larger capture effect than identical distractors in the…

  19. Boron neutron capture therapy for cancer

    SciTech Connect

    Barth, R.E.; Soloway, A.H. ); Fairchild, R.G. State Univ. of New York, Stony Brook )

    1990-10-01

    Boron neutron capture therapy (BNCT) bring together two components that when kept separate have only minor effects on normal cells. The first component is a stable isotope of boron (boron 10) that can be concentrated in tumor cells. The second is a beam of low-energy neutrons that produces short-range radiation when absorbed, or captured, by the boron. The combination of these two conditions at the site of a tumor releases intense radiation that can destroy malignant tissues. BNCT is based on the nuclear reaction that occurs when boron 10 is irradiated with an absorbs neutrons. The neutrons that it takes up are called thermal, or slow, neutrons. They are of such low energy that they cause little tissue damage as compared with other forms of radiation such as protons, gamma rays and fast neutrons. When an atom of boron 10 captures a neutron, an unstable isotope, boron 11, forms. The boron 11 instantly fissions, yielding lithium 7 nuclei and energetic alpha particles. These heavy particles, which carry 2.79 million electron volts of energy, are a highly lethal form of radiation. If the treatment proceeds as intended, the destructive effects of the capture reaction would occur primarily in those cancer cells that have accumulated boron 10. Normal cells with low concentrations of boron would be spared.

  20. Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy.

    PubMed

    Luderer, Micah John; de la Puente, Pilar; Azab, Abdel Kareem

    2015-09-01

    Boron neutron capture therapy (BNCT) is a promising cancer therapy modality that utilizes the nuclear capture reaction of epithermal neutrons by boron-10 resulting in a localized nuclear fission reaction and subsequent cell death. Since cellular destruction is limited to approximately the diameter of a single cell, primarily only cells in the neutron field with significant boron accumulation will be damaged. However, the emergence of BNCT as a prominent therapy has in large part been hindered by a paucity of tumor selective boron containing agents. While L-boronophenylalanine and sodium borocaptate are the most commonly investigated clinical agents, new agents are desperately needed due to their suboptimal tumor selectivity. This review will highlight the various strategies to improve tumor boron delivery including: nucleoside and carbohydrate analogs, unnatural amino acids, porphyrins, antibody-dendrimer conjugates, cationic polymers, cell-membrane penetrating peptides, liposomes and nanoparticles.

  1. Recent advances in neutron capture therapy (NCT)

    SciTech Connect

    Fairchild, R.G.

    1985-01-01

    The application of the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction to cancer radiotherapy (Neutron Capture therapy, or NCT) has intrigued investigators since the discovery of the neutron. This paper briefly summarizes data describing recently developed boronated compounds with evident tumor specificity and extended biological half-lives. The implication of these compounds to NCT is evaluated in terms of Therapeutic Gain (TG). The optimization of NCT using band-pass filtered beams is described, again in terms of TG, and irradiation times with these less intense beams are estimated. 24 refs., 3 figs., 3 tabs.

  2. Progress in neutron capture therapy for cancer

    SciTech Connect

    Allen, B.J.; Harrington, B.V. ); Moore, D.E. )

    1992-01-01

    Prognosis for some cancers is good, but for others, few patients will survive 12 months. This latter group of cancers is characterised by a proclivity to disseminate malignant cells in the host organ. In some cases systemic metastases occur, but in other cases, failure to achieve local control results in death. First among these cancers are the high grade brain tumours, astrocytoma 3,4 and glioblastoma multiforme. Local control of these tumors should lead to cure. Other cancers melanoma metastatic to the brain, for which a useful palliative therapy is not yet available, and pancreatic cancer for which localised control at an early stage could bring about improved prognosis. Patients with these cancers have little grounds for hope. Our primary objective is to reverse this situation with Neutron Capture Therapy (NCT). The purpose of this fourth symposium is to hasten the day whereby patients with these cancers can reasonably hope for substantial remissions.

  3. Progress in neutron capture therapy for cancer

    SciTech Connect

    Allen, B.J.; Harrington, B.V.; Moore, D.E.

    1992-09-01

    Prognosis for some cancers is good, but for others, few patients will survive 12 months. This latter group of cancers is characterised by a proclivity to disseminate malignant cells in the host organ. In some cases systemic metastases occur, but in other cases, failure to achieve local control results in death. First among these cancers are the high grade brain tumours, astrocytoma 3,4 and glioblastoma multiforme. Local control of these tumors should lead to cure. Other cancers melanoma metastatic to the brain, for which a useful palliative therapy is not yet available, and pancreatic cancer for which localised control at an early stage could bring about improved prognosis. Patients with these cancers have little grounds for hope. Our primary objective is to reverse this situation with Neutron Capture Therapy (NCT). The purpose of this fourth symposium is to hasten the day whereby patients with these cancers can reasonably hope for substantial remissions.

  4. Microdosimetry for Boron Neutron Capture Therapy

    SciTech Connect

    Maughan, R.L.; Kota, C.

    2000-09-05

    The specific aims of the research proposal were as follows: (1) To design and construct small volume tissue equivalent proportional counters for the dosimetry and microdosimetry of high intensity thermal and epithermal neutron beams used in BNCT, and of modified fast neutron beams designed for boron neutron capture enhanced fast neutron therapy (BNCEFNT). (2) To develop analytical methods for estimating the biological effectiveness of the absorbed dose in BNCT and BNCEFNT based on the measured microdosimetric spectra. (3) To develop an analytical framework for comparing the biological effectiveness of different epithermal neutron beams used in BNCT and BNCEFNT, based on correlated sets of measured microdosimetric spectra and radiobiological data. Specific aims (1) and (2) were achieved in their entirety and are comprehensively documented in Jay Burmeister's Ph.D. dissertation entitled ''Specification of physical and biologically effective absorbed dose in radiation therapies utilizing the boron neutron capture reaction'' (Wayne State University, 1999). Specific aim (3) proved difficult to accomplish because of a lack of sufficient radiobiological data.

  5. Neutron dosimetry in boron neutron capture therapy

    SciTech Connect

    Fairchild, R.G.; Miola, U.J.; Ettinger, K.V.

    1981-01-01

    The recent development of various borated compounds and the utilization of one of these (Na/sub 2/B/sub 12/H/sub 11/SH) to treat brain tumors in clinical studies in Japan has renewed interest in neutron capture therapy. In these procedures thermal neutrons interact with /sup 10/B in boron containing cells through the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction producing charged particles with a maximum range of approx. 10..mu..m in tissue. Borated analogs of chlorpromazine, porphyrin, thiouracil and deoxyuridine promise improved tumor uptake and blood clearance. The therapy beam from the Medical Research Reactor in Brookhaven contains neutrons from a modified and filtered fission spectrum and dosimetric consequences of the use of the above mentioned compounds in conjunction with thermal and epithermal fluxes are discussed in the paper. One of the important problems of radiation dosimetry in capture therapy is determination of the flux profile and, hence, the dose profile in the brain. This has been achieved by constructing a brain phantom made of TE plastic. The lyoluminescence technique provides a convenient way of monitoring the neutron flux distributions; the detectors for this purpose utilize /sup 6/Li and /sup 10/B compounds. Such compounds have been synthesized specially for the purpose of dosimetry of thermal and epithermal beams. In addition, standard lyoluminescent phosphors, like glutamine, could be used to determine the collisional component of the dose as well as the contribution of the /sup 14/N(n,p)/sup 14/C reaction. Measurements of thermal flux were compared with calculations and with measurements done with activation foils.

  6. Accelerator-driven boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Edgecock, Rob

    2014-05-01

    Boron Neutron Capture Therapy is a binary treatment for certain types of cancer. It works by loading the cancerous cells with a boron-10 carrying compound. This isotope has a large cross-section for thermal neutrons, the reaction producing a lithium nucleus and alpha particle that kill the cell in which they are produced. Recent studies of the boron carrier compound indicate that the uptake process works best in particularly aggressive cancers. Most studied is glioblastoma multiforme and a trial using a combination of BNCT and X-ray radiotherapy has shown an increase of nearly a factor of two in mean survival over the state of the art. However, the main technical problem with BNCT remains producing a sufficient flux of neutrons for a reasonable treatment duration in a hospital environment. This paper discusses this issue.

  7. Boron Neutron Capture Therapy - A Literature Review

    PubMed Central

    Nedunchezhian, Kavitaa; Thiruppathy, Manigandan; Thirugnanamurthy, Sarumathi

    2016-01-01

    Boron Neutron Capture Therapy (BNCT) is a radiation science which is emerging as a hopeful tool in treating cancer, by selectively concentrating boron compounds in tumour cells and then subjecting the tumour cells to epithermal neutron beam radiation. BNCT bestows upon the nuclear reaction that occurs when Boron-10, a stable isotope, is irradiated with low-energy thermal neutrons to yield α particles (Helium-4) and recoiling lithium-7 nuclei. A large number of 10 Boron (10B) atoms have to be localized on or within neoplastic cells for BNCT to be effective, and an adequate number of thermal neutrons have to be absorbed by the 10B atoms to maintain a lethal 10B (n, α) lithium-7 reaction. The most exclusive property of BNCT is that it can deposit an immense dose gradient between the tumour cells and normal cells. BNCT integrates the fundamental focusing perception of chemotherapy and the gross anatomical localization proposition of traditional radiotherapy. PMID:28209015

  8. Boron neutron capture therapy: Moving toward targeted cancer therapy.

    PubMed

    Mirzaei, Hamid Reza; Sahebkar, Amirhossein; Salehi, Rasoul; Nahand, Javid Sadri; Karimi, Ehsan; Jaafari, Mahmoud Reza; Mirzaei, Hamed

    2016-01-01

    Boron neutron capture therapy (BNCT) occurs when a stable isotope, boton-10, is irradiated with low-energy thermal neutrons to yield stripped down helium-4 nuclei and lithium-7 nuclei. It is a binary therapy in the treatment of cancer in which a cytotoxic event is triggered when an atom placed in a cancer cell. Here, we provide an overview on the application of BNCT in cancer therapy as well as current preclinical and clinical evidence on the efficacy of BNCT in the treatment of melanoma, brain tumors, head and neck cancer, and thyroid cancer. Several studies have shown that BNCT is effective in patients who had been treated with a full dose of conventional radiotherapy, because of its selectivity. In addition, BNCT is dependent on the normal/tumor tissue ratio of boron distribution. Increasing evidence has shown that BNCT can be combined with different drug delivery systems to enhance the delivery of boron to cancer cells. The flexibility of BNCT to be used in combination with different tumor-targeting approaches has made this strategy a promising option for cancer therapy. This review aims to provide a state-of-the-art overview of the recent advances in the use of BNCT for targeted therapy of cancer.

  9. Historic Methods for Capturing Magnetic Field Images

    ERIC Educational Resources Information Center

    Kwan, Alistair

    2016-01-01

    I investigated two late 19th-century methods for capturing magnetic field images from iron filings for historical insight into the pedagogy of hands-on physics education methods, and to flesh out teaching and learning practicalities tacit in the historical record. Both methods offer opportunities for close sensory engagement in data-collection…

  10. Historic Methods for Capturing Magnetic Field Images

    NASA Astrophysics Data System (ADS)

    Kwan, Alistair

    2016-03-01

    I investigated two late 19th-century methods for capturing magnetic field images from iron filings for historical insight into the pedagogy of hands-on physics education methods, and to flesh out teaching and learning practicalities tacit in the historical record. Both methods offer opportunities for close sensory engagement in data-collection processes.

  11. Liposomal boron delivery for neutron capture therapy.

    PubMed

    Nakamura, Hiroyuki

    2009-01-01

    Tumor cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. The thermal neutrons have an energy of 0.025 eV, clearly below the threshold energy required to ionize tissue components. However, neutron capture by (10)B produces lithium ion and helium (alpha-particles), which are high linear energy transfer (LET) particles, and dissipate their kinetic energy before traveling one cell diameter (5-9 microm) in biological tissues, ensuring their potential for precise cell killing. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer, and hepatoma using two boron compounds: sodium borocaptate (Na(2)(10)B(12)H(11)SH; Na(2)(10)BSH) and l-p-boronophenylalanine (l-(10)BPA). These low molecular weight compounds are cleared easily from the cancer cells and blood. Therefore, high accumulation and selective delivery of boron compounds into tumor tissues are most important to achieve effective BNCT and to avoid damage of adjacent healthy cells. Much attention has been focused on the liposomal drug delivery system (DDS) as an attractive, intelligent technology of targeting and controlled release of (10)B compounds. Two approaches have been investigated for incorporation of (10)B into liposomes: (1) encapsulation of (10)B compounds into liposomes and (2) incorporation of (10)B-conjugated lipids into the liposomal bilayer. Our laboratory has developed boron ion cluster lipids for application of the latter approach. In this chapter, our boron lipid liposome approaches as well as recent developments of the liposomal boron delivery system are summarized.

  12. Boron neutron capture therapy (BNCT): A radiation oncology perspective

    SciTech Connect

    Dorn, R.V. III Idaho National Engineering Lab., Idaho Falls, ID )

    1994-03-30

    Boron neutron capture therapy (BNCT) offers considerable promise in the search for the ideal cancer therapy, a therapy which selectively and maximally damages malignant cells while sparing normal tissue. This bimodal treatment modality selectivity concentrates a boron compound in malignant cells, and then [open quotes]activates[close quotes] this compound with slow neutrons resulting in a highly lethal event within the cancer cell. This article reviews this treatment modality from a radiation oncology, biology, and physics perspective. The remainder of the articles in this special issue provide a survey of the current [open quotes]state-of-the-art[close quotes] in this rapidly expanding field, including information with regard to boron compounds and their localization. 118 refs., 3 figs.

  13. Neutron capture therapy research in Australia.

    PubMed

    Allen, B J

    1989-01-01

    Neutron capture therapy research in Australia has continued to grow since the first Australia-Japan workshop in April, 1986. The support base has broadened and the wide range of contributing laboratories includes universities, research institutes, and hospitals. Considerable progress has been made in boron chemistry--an accurate boron assay technique has been developed, boron analogues of chlorpromazine and thiouracil have been synthesised or nearly so, and decaborane conjugation with monoclonal antibodies has been achieved to the required loadings. In vitro cell survival experiments are proceeding in the Moata reactor using human melanoma and mouse cell lines incubated with enriched boronophenylalanine and boron tetraphenyl porphyrins. Electron microscopy examination of radiation damaged morphology shows considerable differences between cell lines. Progress with the nude mouse human melanoma model has been slow because of the lack of a reliable in vivo melanotic melanoma line, and the B16 mouse line is found to be more efficacious. Tailored beam calculations for the 10 MW HIFAR reactor indicate the difficulty of obtaining a suitable therapeutic beam because of the generated gamma dose in the beam filters. A new approach to NCT utilises the enormous cross section of 157Gd and the induced-Auger effect which has been shown to cause double strand breaks in circular DNA.

  14. Neutron capture therapy research in Australia

    SciTech Connect

    Allen, B.J.

    1989-07-01

    Neutron capture therapy research in Australia has continued to grow since the first Australia-Japan workshop in April, 1986. The support base has broadened and the wide range of contributing laboratories includes universities, research institutes, and hospitals. Considerable progress has been made in boron chemistry--an accurate boron assay technique has been developed, boron analogues of chlorpromazine and thiouracil have been synthesised or nearly so, and decaborane conjugation with monoclonal antibodies has been achieved to the required loadings. In vitro cell survival experiments are proceeding in the Moata reactor using human melanoma and mouse cell lines incubated with enriched boronophenylalanine and boron tetraphenyl porphyrins. Electron microscopy examination of radiation damaged morphology shows considerable differences between cell lines. Progress with the nude mouse human melanoma model has been slow because of the lack of a reliable in vivo melanotic melanoma line, and the B16 mouse line is found to be more efficacious. Tailored beam calculations for the 10 MW HIFAR reactor indicate the difficulty of obtaining a suitable therapeutic beam because of the generated gamma dose in the beam filters. A new approach to NCT utilises the enormous cross section of 157Gd and the induced-Auger effect which has been shown to cause double strand breaks in circular DNA. 34 references.

  15. Research needs for neutron capture therapy

    SciTech Connect

    1995-12-01

    Key issues and questions addressed by the workshop related to optimization of Boron Neutron Capture Therapy (BNCT), in general, and to the possibility of success of the present BNCT trials at Brookhaven National Laboratory (BNL) and Massachusetts Institute of Technology (MIT), in particular. Both trials use nuclear fission reactors as neutron sources for BNCT of glioblastoma multiforme (BNL) and of deep seated melanoma (MIT). Presentations and discussions focussed on optimal boron-labeled compounds, mainly for brain tumors such as glioblastoma multiforme, and the best mode of compound delivery to the tumor. Also, optimizing neutron irradiation with dose delivery to the tumor cells and the issues of dosimetry of BNCT especially in the brain were discussed. Planning of treatment and of follow-up of patients, coordination of BNCT at various treatment sites, and the potential of delivering BNCT to various types of cancer with an appropriately tailored protocol were additional issues. The need for multicentric interdisciplinary cooperation among the different medical specialties was highlighted.

  16. Neutron capture therapy: Years of experimentation---Years of reflection

    SciTech Connect

    Farr, L.E.

    1991-12-16

    This report describes early research on neutron capture therapy over a number of years, beginning in 1950, speaking briefly of patient treatments but dwelling mostly on interpretations of our animal experiments. This work carried out over eighteen years, beginning over forty years ago. Yet, it is only fitting to start by relating how neutron capture therapy became part of Brookhaven's Medical Research Center program.

  17. The radiation biology of boron neutron capture therapy.

    PubMed

    Coderre, J A; Morris, G M

    1999-01-01

    Boron neutron capture therapy (BNCT) is a targeted radiation therapy that significantly increases the therapeutic ratio relative to conventional radiotherapeutic modalities. BNCT is a binary approach: A boron-10 (10B)-labeled compound is administered that delivers high concentrations of 10B to the target tumor relative to surrounding normal tissues. This is followed by irradiation with thermal neutrons or epithermal neutrons which become thermalized at depth in tissues. The short range (5-9 microm) of the alpha and 7Li particles released from the 10B(n,alpha)7Li neutron capture reaction make the microdistribution of 10B of critical importance in therapy. The radiation field in tissues during BNCT consists of a mixture of components with differing LET characteristics. Studies have been carried out in both normal and neoplastic tissues to characterize the relative biological effectiveness of each radiation component. The distribution patterns and radiobiological characteristics of the two 10B delivery agents in current clinical use, the amino acid p-boronophenylalanine (BPA) and the sulfhydryl borane (BSH), have been evaluated in a range of normal tissues and tumor types. Considered overall, BSH-mediated BNCT elicits proportionately less damage to normal tissue than does BNCT mediated with BPA. However, BPA exhibits superior in vivo tumor targeting and has proven much more effective in the treatment of brain tumors in rats. In terms of fractionation effects, boron neutron capture irradiation modalities are comparable with other high-LET radiation modalities such as fast-neutron therapy. There was no appreciable advantage in increasing the number of daily fractions of thermal neutrons beyond two with regard to sparing of normal tissue in the rat spinal cord model. The experimental studies described in this review constitute the radiobiological basis for the new BNCT clinical trials for glioblastoma at Brookhaven National Laboratory, at the Massachusetts Institute of

  18. [Boron neutron capture therapy (BNCT) as cancer treatment].

    PubMed

    Joensuu, Heikki; Kankaanranta, Leena; Tenhunen, Mikko; Saarilahti, Kauko

    2011-01-01

    Boron neutron capture therapy leads to a strong local radiotherapy effect. The efficacy of the method in cancer therapy requires sufficient accumulation of boron into and a fairly superficial location of the tumor. The efficacy and tolerability of this therapy has been investigated in Finland especially in locally recurring head and neck cancer. These tumors have responded favorably to boron neutron capture therapy and the treatment has been relatively well tolerated, although most cancers have recurred locally with few cases of durable complete remission.

  19. Neutron capture therapy: Years of experimentation---Years of reflection

    SciTech Connect

    Farr, L.E.

    1991-12-16

    This report describes early research on neutron capture therapy over a number of years, beginning in 1950, speaking briefly of patient treatments but dwelling mostly on interpretations of our animal experiments. This work carried out over eighteen years, beginning over forty years ago. Yet, it is only fitting to start by relating how neutron capture therapy became part of Brookhaven`s Medical Research Center program.

  20. Proton linacs for boron neutron capture therapy

    SciTech Connect

    Lennox, A.J. |

    1993-08-01

    Recent advances in the ability to deliver boron-containing drugs to brain tumors have generated interest in {approximately}4 MeV linacs as sources of epithermal neutrons for radiation therapy. In addition, fast neutron therapy facilities have been studying methods to moderate their beams to take advantage of the high cross section for epithermal neutrons on boron-10. This paper describes the technical issues involved in each approach and presents the motivation for undertaking such studies using the Fermilab linac. the problems which must be solved before therapy can begin are outlined. Status of preparatory work and results of preliminary measurements are presented.

  1. New compounds for neutron capture therapy (NCT) and their significance

    SciTech Connect

    Fairchild, R.G.; Bond, V.P.

    1982-01-01

    Clearly the most effective tumor therapy would be obtained by the selective targeting of cytotoxic agents to tumor cells. Although many biomolecules are known to be taken up in tumors, the targeting of cytotoxic agents to tumors is limited by the fact that other essential cell pools compete with equal or even greater effectiveness. The approach of delivering stable non-toxic isotopes to tumor, with activation by means of an external radiation beam, is advantageous for two reasons: (1) it obviates problems associated with high uptake of isotopes in normal tissues, as these cell pools can be excluded from the radiation field, and (2) the general tumor area can be included in the activating beam field; thus, the possibility exists that all microscopic tumor extensions can be irradiated. As long as range of reaction products is short, dose will be restricted to the tumor, with a resultant high therapeutic ratio. This method can be accomplished with either photon activation therapy (PAT) or Neutron Capture Therapy (NCT), the latter will be emphasized here. The range of the high LET, low OER particles from the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction is approx. 10 ..mu..m, or one cell diameter; hence this reaction is optimal for cell killing. A number of biomolecules have been investigated as possible vehicles for transport of boron to tumors, including phenothiazines, thiouracils, porphyrins, nucleosides, and amino acids. Biodistributions of these compounds show selective concentration in tumor adequate for therapy. The biological halflives are in the order of days, allowing the possibility of fractionated or protracted irradiations. The radiobiological and physical implication of these parameters on NCT are discussed. The possibility of using an approximately-monoenergetic, scandium-filtered beam of about 2 keV, to reduce the dose from background radiations by about 85%, is also discussed. (ERB)

  2. Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

    DOEpatents

    Miura, Michiko; Slatkin, Daniel N.

    1997-03-18

    A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na.sub.4 B.sub.12 I.sub.11 SSB.sub.12 I.sub.11, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy.

  3. Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

    DOEpatents

    Miura, Michiko; Slatkin, Daniel N.

    1995-10-03

    A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na.sub.4 B.sub.12 I.sub.11 SSB.sub.12 I.sub.11, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy.

  4. Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

    DOEpatents

    Miura, Michiko; Slatkin, Daniel N.

    1997-08-05

    A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized. by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na.sub.4 B.sub.12 I.sub.11 SSB.sub.12 I.sub.11, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy.

  5. Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

    DOEpatents

    Miura, M.; Slatkin, D.N.

    1995-10-03

    A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na{sub 4}B{sub 12}I{sub 11}SSB{sub 12}I{sub 11}, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy. 1 fig.

  6. Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

    DOEpatents

    Miura, M.; Slatkin, D.N.

    1997-03-18

    A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na{sub 4}B{sub 12}I{sub 11}SSB{sub 12}I{sub 11}, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy. 1 fig.

  7. Halogenated sulfidohydroboranes for nuclear medicine and boron neutron capture therapy

    DOEpatents

    Miura, M.; Slatkin, D.N.

    1997-08-05

    A method for performing boron neutron capture therapy for the treatment of tumors is disclosed. The method includes administering to a patient an iodinated sulfidohydroborane, a boron-10-containing compound. The site of the tumor is localized by visualizing the increased concentration of the iodine labelled compound at the tumor. The targeted tumor is then irradiated with a beam of neutrons having an energy distribution effective for neutron capture. Destruction of the tumor occurs due to high LET particle irradiation of the tissue secondary to the incident neutrons being captured by the boron-10 nuclei. Iodinated sulfidohydroboranes are disclosed which are especially suitable for the method of the invention. In a preferred embodiment, a compound having the formula Na{sub 4}B{sub 12}I{sub 11}SSB{sub 12}I{sub 11}, or another pharmaceutically acceptable salt of the compound, may be administered to a cancer patient for boron neutron capture therapy. 1 fig.

  8. Neutron beam design, development, and performance for neutron capture therapy

    SciTech Connect

    Harling, O.K.; Bernard, J.A. ); Zamenhof, R.G. )

    1990-01-01

    The report presents topics presented at a workshop on neutron beams and neutron capture therapy. Topics include: neutron beam design; reactor-based neutron beams; accelerator-based neutron beams; and dosimetry and treatment planning. Individual projects are processed separately for the databases. (CBS)

  9. Head phantom experiment and calculation for boron neutron capture therapy.

    PubMed

    Matsumoto, T; Aizawa, O

    1988-06-01

    Head phantom experiments with various neutron beams and calculations were carried out in order to provide useful information for boron neutron capture therapy (BNCT). Thermal neutron beams for thermal neutron capture therapy were used for phantom experiments with various neutron collimator aperture sizes. The filtered beam neutrons of 24 and 144 keV generated with iron and silicon filters were also used to investigate the possible application of BNCT in the treatment of deep-seated cancers. Thermal neutron fluence and induced capture gamma dose distributions within the phantom were calculated with a transport code DOT 3.5 and compared with the experimental results. The results showed that the calculation used was consistent with the experimental results and provided useful information on BNCT. The filtered beam neutron may be very useful for the treatment of deep or widespread cancer, if there were a high power research reactor constructed for this purpose.

  10. Target studies for accelerator-based boron neutron capture therapy

    SciTech Connect

    Powell, J.R.; Ludewig, H.; Todosow, M.; Reich, M.

    1996-03-01

    Two new concepts, NIFTI and DISCOS, are described. These concepts enable the efficient production of epithermal neutrons for BNCT (Boron Neutron Capture Therapy) medical treatment, utilizing a low current, low energy proton beam impacting on a lithium target. The NIFTI concept uses an iron layer that strongly impedes the transmission of neutrons with energies above 24 KeV. Lower energy neutrons readily pass through this iron ``filter``, which has a deep ``window`` in its scattering cross section at 24 KeV. The DISCOS concept uses a rapidly rotating, high g disc to create a series of thin ({approximately} 1 micron thickness) liquid lithium targets in the form of continuous films through which the proton beam passes. The average energy lost by a proton as it passes through a single target is small, approximately 10 KeV. Between the targets, the proton beam is reaccelerated by an applied DC electric field. The DISCOS approach enables the accelerator -- target facility to operate with a beam energy only slightly above the threshold value for neutron production -- resulting in an output beam of low-energy epithermal neutrons -- while achieving a high yield of neutrons per milliamp of proton beam current.

  11. Boron neutron capture therapy at the crossroads: challenges and opportunities.

    PubMed

    Barth, Rolf F

    2009-07-01

    Over the past 25 years research on boron neutron capture therapy (BNCT) has progressed relatively slowly but steadily with the greatest progress in the field of clinical studies. These specifically have included the use of BNCT to treat a variety of malignancies other than high grade gliomas and melanomas. However, there are a number of key areas where little, if any, significant progress has been made. First and foremost among these has been the lack of new boron delivery agents. Improvement in drug delivery and the development of the best dosing paradigms for both boronophenylalanine (BPA) and sodium borocaptate (BSH) are of major importance and these still have not been optimized. Dosimetry for BNCT is still imprecise and is based on treating to normal tissue tolerance, based on blood boron values, rather than any real-time information on the boron content of the residual tumor that is to be irradiated. Another major problem has been the total dependence on nuclear reactors as neutron sources for BNCT. However, this will change in the near future when a clinically useful accelerator comes into use in 2009. Like it or not, in order to gain the credibility of a broad community of physicians who treat brain tumor patients, there will have to be a randomized clinical trial. Finally, BNCT will have to compete with new therapeutic approaches that are less costly and more effective for the treatment of brain tumors. These challenges notwithstanding, BNCT can fill an important niche for those malignancies, whether primary or recurrent, for which there is currently no effective therapy.

  12. [Minimally invasive cytoselective radiation therapy using boron neutron capture reaction].

    PubMed

    Nakamura, Hiroyuki

    2010-12-01

    The cell-killing effect of boron neutron capture therapy (BNCT) is due to the nuclear reaction of two essentially nontoxic species, boron-10 ((10)B) and thermal neutrons, whose destructive effect is well observed in boron-loaded tissues. High accumulation and selective delivery of boron into tumor tissue are the most important requirements to achieve efficient neutron capture therapy of cancers. This review focuses on liposomal boron delivery system (BDS) as a recent promising approach that meet these requirements for BNCT. BDS involves two strategies: (1) encapsulation of boron in the aqueous core of liposomes and (2) accumulation of boron in the liposomal bilayer. In this review, recent development of liposomal boron delivery system is summarized.

  13. Theoretical and experimental physical methods of neutron-capture therapy

    NASA Astrophysics Data System (ADS)

    Borisov, G. I.

    2011-09-01

    This review is based to a substantial degree on our priority developments and research at the IR-8 reactor of the Russian Research Centre Kurchatov Institute. New theoretical and experimental methods of neutron-capture therapy are developed and applied in practice; these are: A general analytical and semi-empiric theory of neutron-capture therapy (NCT) based on classical neutron physics and its main sections (elementary theories of moderation, diffuse, reflection, and absorption of neutrons) rather than on methods of mathematical simulation. The theory is, first of all, intended for practical application by physicists, engineers, biologists, and physicians. This theory can be mastered by anyone with a higher education of almost any kind and minimal experience in operating a personal computer.

  14. Research in Boron Neutron Capture Therapy at MIT LABA

    SciTech Connect

    Yanch, J.C.; Shefer, R.E.; Klinkowstein, R.E.; Howard, W.B.; Song, H.; Blackburn, B.; Binello, E.

    1997-02-01

    A 4.1 MeV tandem electrostatic accelerator designed for research into Boron Neutron Capture Therapy (BNCT) has recently been installed in the MIT Laboratory for Accelerator Beam Applications (LABA). This accelerator uses a very high current switch mode high voltage power supply in conjunction with a multi-cusp negative ion source to supply the multimilliampere current required for clinical BNCT applications. A number of individual research projects aimed at evaluating the potential of this accelerator design as a hospital-based neutron source for radiation therapy of both tumors and rheumatoid arthritis are described here. {copyright} {ital 1997 American Institute of Physics.}

  15. Carborane derivative development for boron neutron capture therapy. Final report

    SciTech Connect

    Barnum, Beverly A.; Yan Hao; Moore, Roger; Hawthorne, M. Frederick; Baum, Kurt

    1999-04-01

    Boron Neutron Capture Therapy [BNCT] is a binary method of cancer therapy based on the capture of neutrons by a boron-10 atom [{sup 10}B]. Cytotoxic {sup 7}Li nuclei and {alpha}-particles are emitted, with a range in tissue of 9 and 5 {micro}m, respectively, about one cell diameter. The major obstacle to clinically viable BNCT is the selective localization of 5-30 ppm {sup 10}B in tumor cells required for effective therapy. A promising approach to BNCT is based on hydrophilic boron-rich oligomeric phosphate diesters, or ''trailers'' that have been shown to concentrate selectively in tumor tissue. Examples of these compounds were prepared previously at high cost using an automated DNA synthesizer. Direct synthesis methods are needed for the production of gram-scale quantities for further biological evaluation. The work accomplished as a result of the collaboration between Fluorochem, Inc. and UCLA demonstrates that short oligomers containing at least five carborane units with four phosphodiester linkages can be prepared in substantial quantities. This work was accomplished by the application of standard phosphoramidite coupling chemistry.

  16. Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model

    SciTech Connect

    A. Monti Hughes; ECC Pozzi; S. Thorp; M. A. Garabalino; R. O. Farias; S. J. Gonzalez; E. M. Heber; M. E. Itoiz; R. F. Aromando; A. J. Molinari; M. Miller; D. W. Nigg; P. Curotto; V. A. Trivillin; A. E. Schwint

    2013-11-01

    Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model.

  17. Boron neutron capture therapy for malignant melanoma: An experimental approach

    SciTech Connect

    Larsson, B.S.; Larsson, B.; Roberto, A. )

    1989-07-01

    Previous studies have shown that some thioamides, e.g., thiouracil, are incorporated as false precursors into melanin during its synthesis. If boronated analogs of the thioamides share this property, the melanin of melanotic melanomas offers a possibility for specific tumoural uptake and retention of boron as a basis for neutron capture therapy. We report on the synthesis of boronated 1H-1,2,4-triazole-3-thiol (B-TZT), boronated 5-carboxy-2-thiouracil (B-CTU), and boronated 5-diethylaminomethyl-2-thiouracil (B-DEAMTU) and the localization of these substances in melanotic melanomas transplanted to mice. The distribution in the mice was studied by boron neutron capture radiography. B-TZT and B-CTU showed the highest tumour:normal tissue concentration ratios, with tumour:liver ratios of about 4 and tumour:muscle ratios of about 14; B-DEAMTU showed corresponding ratios of 1.4 and 5, respectively. The absolute concentration of boron in the tumours, however, was more than three times higher in the mice injected with B-TZT, compared with B-CTU. The results suggest that B-TZT may be the most promising compound of the three tested with regard to possible therapy of melanotic melanomas.

  18. Strategic planning workshop on research needs for neutron capture therapy.

    PubMed

    Feinendegen, L E

    1997-05-01

    The workshop 'Research Needs for Neutron Capture Therapy', held in Williamsburg, VA, May 9-12. 1995 addressed key issues and questions related to optimization of boron neutron capture therapy (BNCT), in general, and to the possibility of success of the present BNCT trials at the Brookhaven National Laboratory (BNL) and Massachusetts Institute of Technology (MIT), in particular. Both trials use nuclear fission reactors as neutron sources for BNCT of glioblastoma multiforme (BNL) and of deep seated melanoma (MIT). Presentations and discussions focussed on optimal boron-labeled compounds, mainly for brain tumors such as glioblastoma multiforme, and the best mode of compound delivery to the tumor. Also, optimizing neutron irradiation with dose delivery to the tumor cells and the issues of dosimetry of BNCT especially in the brain were discussed. Planning of treatment and of follow-up of patients, coordination of BNCT at various treatment sites, and the potential of delivery BNCT to various types of cancer with an appropriately tailored protocol were additional issues. The need for multicentric interdisciplinary cooperation among the different medical specialties was highlighted.

  19. Towards epithermal Boron Neutron Capture Therapy for cancer

    SciTech Connect

    Allen, B.J.

    1994-12-31

    Progress in the treatment of local disseminating cancer such as high grade brain tumours is poor, and the ability to kill individual cancer cells in the midst of normal cells has not been achieved. Binary therapies hold the most promise of this, and of these Boron Neutron Capture Therapy is the most advanced. Epithermal neutron beams are essential for outpatient treatment of high grade brain tumours and these are now installed and being characterised in Europe and the USA, and are at the design stage in Australia. These beams would allow the bilateral irradiation of the entire brain, and as such are ideally suited for the prophylactic therapy of subclinical metastases. When coupled with appropriate cancer affined boron compounds, therapeutic ratios of 2-3 should be achieved. At present the only source of an epithermal neutron beam is a nuclear reactor. The Euratom reactor at Petten and the Brookhaven Medical Reactor have been retrofitted with filters to produce an epithermal neutron beam. These beams have been characterised and used in dose escalation studies with dogs to study normal tissue tolerance using borocaptate (BSH). Another beam is available at the MIT medical research reactor. Clinical trials at Petten for glioblastoma with BSH and at MIT using boronophenylalanine for melanoma metastases to the extremities are expected to commence this year. The state of the art of reactor based BNCT is reviewed and the potential for a major change in the prognosis of local control of disseminating cancer is explored.

  20. Evaluation of absorbed dose in Gadolinium neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Abdullaeva, Gayane; Djuraeva, Gulnara; Kim, Andrey; Koblik, Yuriy; Kulabdullaev, Gairatulla; Rakhmonov, Turdimukhammad; Saytjanov, Shavkat

    2015-02-01

    Gadolinium neutron capture therapy (GdNCT) is used for treatment of radioresistant malignant tumors. The absorbed dose in GdNCT can be divided into four primary dose components: thermal neutron, fast neutron, photon and natural gadolinium doses. The most significant is the dose created by natural gadolinium. The amount of gadolinium at the irradiated region is changeable and depends on the gadolinium delivery agent and on the structure of the location where the agent is injected. To de- fine the time dependence of the gadolinium concentration ρ(t) in the irradiated region the pharmacokinetics of gadolinium delivery agent (Magnevist) was studied at intratumoral injection in mice and intramuscular injection in rats. A polynomial approximation was applied to the experimental data and the influence of ρ(t) on the relative change of the absorbed dose of gadolinium was studied.

  1. Boron neutron capture therapy for the prevention of restenosis

    SciTech Connect

    Yanch, J.C.; Delfaus, M.L.

    1997-12-01

    The potential application of boron neutron capture therapy (BNCT) for the prevention of restenosis following angioplasty is under investigation at Massachusetts Institute of Technology`s Laboratory for Accelerator Beam Applications. The process of Percutaneous transluminal coronary angioplasty involves the insertion of a balloon dilation catheter into the occluded artery. The balloon is then inflated for several minutes to dilate the artery. The blockage is decreased, and blood flow through the artery is improved. This procedure is, initially, very successful. However, 30 to 60% of patients treated also show restenosis within 6 months. Although many physiological processes may contribute to restenosis, the primary mechanism is thought to be abnormal proliferation of the smooth muscle cells in the treated artery.

  2. A Compact Neutron Source for Boron Neutron Capture Therapy

    NASA Astrophysics Data System (ADS)

    Golubev, S. V.; Izotov, I. V.; Razin, S. V.; Sidorov, A. V.; Skalyga, V. A.

    2017-01-01

    We propose a neutron generator scheme based on a high-current ion source with electron cyclotron resonance plasma heating by high-power millimeter-wave gyrotron radiation. The most promising application of this neutron generator is a medical one, namely, boron neutron capture therapy of oncological diseases. A possibility for using a multi-aperture extraction system for high-current ion beam generation to increase the total current is studied. It is shown that the parameters of the plasma flow leaving a magnetic trap permit the effective use of multi-aperture systems without a significant loss in the ion beam current density. Thus, the use of multi-aperture systems in the ion source of a neutron generator can significantly increase the total neutron yield.

  3. Boron Neutron Capture Therapy for Malignant Brain Tumors

    PubMed Central

    MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  4. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    PubMed

    Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

    2016-07-15

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting.

  5. Computational Dosimetry and Treatment Planning Considerations for Neutron Capture Therapy

    SciTech Connect

    Nigg, David Waler

    2003-03-01

    Specialized treatment planning software systems are generally required for neutron capture therapy (NCT) research and clinical applications. The standard simplifying approximations that work well for treatment planning computations in the case of many other modalities are usually not appropriate for application to neutron transport. One generally must obtain an explicit three-dimensional numerical solution of the governing transport equation, with energy-dependent neutron scattering completely taken into account. Treatment planning systems that have been successfully introduced for NCT applications over the past 15 years rely on the Monte Carlo stochastic simulation method for the necessary computations, primarily because of the geometric complexity of human anatomy. However, historically, there has also been interest in the application of deterministic methods, and there have been some practical developments in this area. Most recently, interest has turned toward the creation of treatment planning software that is not limited to any specific therapy modality, with NCT as only one of several applications. A key issue with NCT treatment planning has to do with boron quantification, and whether improved information concerning the spatial biodistribution of boron can be effectively used to improve the treatment planning process. Validation and benchmarking of computations for NCT are also of current developmental interest. Various institutions have their own procedures, but standard validation models are not yet in wide use.

  6. Thiourea derivatives, methods of their preparation and their use in neutron capture therapy of malignant melanoma

    DOEpatents

    Gabel, D.

    1991-06-04

    The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

  7. Boron containing compounds and their preparation and use in neutron capture therapy

    DOEpatents

    Gabel, D.

    1992-09-01

    The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

  8. The accelerator neutron source for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Kasatov, D.; Koshkarev, A.; Kuznetsov, A.; Makarov, A.; Ostreinov, Yu; Shchudlo, I.; Sorokin, I.; Sycheva, T.; Taskaev, S.; Zaidi, L.

    2016-11-01

    The accelerator based epithermal neutron source for Boron Neutron Capture Therapy (BNCT) is proposed, created and used in the Budker Institute of Nuclear Physics. In 2014, with the support of the Russian Science Foundation created the BNCT laboratory for the purpose to the end of 2016 get the neutron flux, suitable for BNCT. For getting 3 mA 2.3 MeV proton beam, was created a new type accelerator - tandem accelerator with vacuum isolation. On this moment, we have a stationary proton beam with 2.3 MeV and current 1.75 mA. Generation of neutrons is carried out by dropping proton beam on to lithium target as a result of threshold reaction 7Li(p,n)7Be. Established facility is a unique scientific installation. It provides a generating of neutron flux, including a monochromatic energy neutrons, gamma radiation, alpha-particles and positrons, and may be used by other research groups for carrying out scientific researches. The article describes an accelerator neutron source, presents and discusses the result of experiments and declares future plans.

  9. Neutron producing target for accelerator based neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Bayanov, B.; Belov, V.; Taskaev, S.

    2006-05-01

    Pilot innovative accelerator based neutron source for neutron capture therapy of cancer is under construction now at the Budker Institute. One of the main elements of the facility is lithium target producing neutrons via threshold 7Li(p, n)7Be reaction at 10 mA proton beam with energies of 1.915 MeV or 2.5 MeV. In the present report, choice of target was substantiated. The main problems of lithium target were determined to be: 7Be radioactive isotope activation, keeping lithium layer solid, presence of photons resulted from proton inelastic scattering on lithium nuclei, and radiation blistering. The results of thermal testing of target prototype, investigation of radiation blistering and several simulations are presented. It becomes clear that water is preferable for cooling this target, and that the lithium target 10 cm in diameter is able to run up to 25 kW proton beam before melting. The conception of optimal target is proposed: thin and easy to detach metal disk 10 cm in diameter, evaporated with thin layer of pure lithium from the side of proton beam exposure: its back is intensively cooled with turbulent water flow to maintain lithium layer solid. Design of target for the neutron source constructed at BINP is shown. Conceptions of radiation protection and neutrons, γ-rays and α- particles diagnostics are presented. The immediate plans on obtaining epithermal neutron beam are declared.

  10. Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

    SciTech Connect

    Herrera, Maria S.; Gonzalez, Sara J.; Minsky, Daniel M.; Kreiner, Andres J.

    2010-08-04

    Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a real patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.

  11. Malignant melanoma cure by selective thermal neutron capture therapy

    SciTech Connect

    Mishima, Y.; Ichihashi, M.; Hatta, S.

    1986-01-01

    Thermal neutrons are easily absorbed by the nonradioactive isotope /sup 10/B, resulting in the emission of alpha particles and lithium atoms, which release an energy of 2.33 MeV for up to a 14-..mu..m-diam melanoma cell. Thus, if /sup 10/B can be selectively accumulated in melanoma, it can be destroyed without injury to the surrounding normal tissues by concentrating high linear energy transfer particles. The authors have synthesized seven melanoma-seeking /sup 10/B compounds, two of which, /sup 10/B12-chlorpromazine(/sup 10/B/sup 12/-CPZ) and /sup 10/B/sub 1/-p-boronophenylalanine(/sup 10/B/sub 1/-BPA), are found to be highly effective. The enhanced melanoma-killing effect of the /sup 10/B compounds is found by in vitro radiobiological analysis. A chemical assay and alpha-track analysis 28 h after systemic administration to melanoma-bearing hamsters reveals a /sup 10/B melanoma/blood ratio of 11.5 and a melanoma/liver ratio of 15. Establishment of a clinical therapeutic method for curing human melanoma without failure is underway by correlating biophysical, biochemical, biological, and therapeutic data analysis. Recently, the authors have also been working to develop neutron capture therapy using /sup 10/B-monoclonal antibodies for melanoma and were able to make some /sup 10/B conjugates with the specific m259-0 antibody.

  12. Neutron tube design study for boron neutron capture therapy application

    SciTech Connect

    Verbeke, J.M.; Lee, Y.; Leung, K.N.; Vujic, J.; Williams, M.D.; Wu, L.K.; Zahir, N.

    1999-05-06

    Radio-frequency (RF) driven ion sources are being developed in Lawrence Berkeley National Laboratory (LBNL) for sealed-accelerator-tube neutron generator application. By using a 5-cm-diameter RF-driven multicusp source H{sup +} yields over 95% have been achieved. These experimental findings will enable one to develop compact neutron generators based on the D-D or D-T fusion reactions. In this new neutron generator, the ion source, the accelerator and the target are all housed in a sealed metal container without external pumping. Recent moderator design simulation studies have shown that 14 MeV neutrons could be moderated to therapeutically useful energy ranges for boron neutron capture therapy (BNCT). The dose near the center of the brain with optimized moderators is about 65% higher than the dose obtained from a typical neutron spectrum produced by the Brookhaven Medical Research Reactor (BMRR), and is comparable to the dose obtained by other accelerator-based neutron sources. With a 120 keV and 1 A deuteron beam, a treatment time of {approx}35 minutes is estimated for BNCT.

  13. Boron containing magnetic nanoparticles for neutron capture therapy--an innovative approach for specifically targeting tumors.

    PubMed

    Tietze, Rainer; Unterweger, Harald; Dürr, Stephan; Lyer, Stefan; Canella, Lea; Kudejova, Petra; Wagner, Franz M; Petry, Winfried; Taccardi, Nicola; Alexiou, Christoph

    2015-12-01

    The selective delivery of (10)B into the tumor tissue remains to be further improved for successful and reliable Boron Neutron Capture Therapy applications. Magnetic Drug Targeting using intraarterially administered superparamagnetic nanoparticles and external magnetic fields already exhibited convincing results in terms of highly efficient and selective drug deposition. Using the same technique for the targeted (10)B delivery is a promising new approach. Here, systematic irradiation experiments of phantom cubes containing different concentrations of boron and nanoparticles as well as varying three-dimensional arrangements have been performed.

  14. Boron neutron capture therapy (BNCT) in Finland: technological and physical prospects after 20 years of experiences.

    PubMed

    Savolainen, Sauli; Kortesniemi, Mika; Timonen, Marjut; Reijonen, Vappu; Kuusela, Linda; Uusi-Simola, Jouni; Salli, Eero; Koivunoro, Hanna; Seppälä, Tiina; Lönnroth, Nadja; Välimäki, Petteri; Hyvönen, Heini; Kotiluoto, Petri; Serén, Tom; Kuronen, Antti; Heikkinen, Sami; Kosunen, Antti; Auterinen, Iiro

    2013-05-01

    Boron Neutron Capture Therapy (BNCT) is a binary radiotherapy method developed to treat patients with certain malignant tumours. To date, over 300 treatments have been carried out at the Finnish BNCT facility in various on-going and past clinical trials. In this technical review, we discuss our research work in the field of medical physics to form the groundwork for the Finnish BNCT patient treatments, as well as the possibilities to further develop and optimize the method in the future. Accordingly, the following aspects are described: neutron sources, beam dosimetry, treatment planning, boron imaging and determination, and finally the possibilities to detect the efficacy and effects of BNCT on patients.

  15. Carboranyl Nucleosides & Oligonucleotides for Neutron Capture Therapy Final Report

    SciTech Connect

    Schinazi, Raymond F.

    2004-12-01

    This proposal enabled us to synthesize and develop boron-rich nucleosides and oligonucleotide analogues for boron neutron capture therapy (BNCT) and the treatment of various malignancies. First, we determined the relationship between structure, cellular accumulation and tissue distribution of 5-o-carboranyl-2'-deoxyuridine (D-CDU) and its derivatives D-ribo-CU and 5-o-carboranyluracil (CU), to potentially target brain and other solid tumors for neutron capture therapy. Synthesized carborane containing nucleoside derivatives of CDU, D- and L-enantiomers of CDU, D-ribo-CU and CU were used. We measured tissue disposition in xenografted mice bearing 9479 human prostate tumors xenografts and in rats bearing 9L gliosarcoma isografts in their flanks and intracranially. The accumulation of D-CDU, 1-({beta}-L-arabinosyl)-5-o-carboranyluracil, D-ribo-CU, and CU were also studied in LnCap human prostate tumor cells and their retention was measured in male nude mice bearing LnCap and 9479 human prostate tumor xenografts. D-CDU, D-ribo-CU and CU levels were measured after administration in mice bearing 9479 human prostate tumors in their flanks. D-CDU achieved high cellular concentrations in LnCap cells and up to 2.5% of the total cellular compound was recovered in the 5'-monophosphorylated form. D-CDU cellular concentrations were similar in LnCap and 9479 tumor xenografts. Studies in tumor bearing animals indicated that increasing the number of hydroxyl moieties in the sugar constituent of the carboranyl nucleosides lead to increased rate and extent of renal elimination, a decrease in serum half-lives and an increased tissue specificity. Tumor/brain ratios were greatest for CDU and D-ribo-CU, while tumor/prostate ratios were greatest with CU. CDU and D-ribo-CU have potential for BNCT of brain malignancies, while CU may be further developed for prostate cancer. A method was developed for the solid phase synthesis of oligonucleotides containing (ocarboran-1-yl

  16. MCNP speed advances for boron neutron capture therapy

    SciTech Connect

    Goorley, J.T.; McKinney, G.; Adams, K.; Estes, G.

    1998-04-01

    The Boron Neutron Capture Therapy (BNCT) treatment planning process of the Beth Israel Deaconess Medical Center-M.I.T team relies on MCNP to determine dose rates in the subject`s head for various beam orientations. In this time consuming computational process, four or five potential beams are investigated. Of these, one or two final beams are selected and thoroughly evaluated. Recent advances greatly decreased the time needed to do these MCNP calculations. Two modifications to the new MCNP4B source code, lattice tally and tracking enhancements, reduced the wall-clock run times of a typical one million source neutrons run to one hour twenty five minutes on a 200 MHz Pentium Pro computer running Linux and using the GNU FORTRAN compiler. Previously these jobs used a special version of MCNP4AB created by Everett Redmond, which completed in two hours two minutes. In addition to this 30% speedup, the MCNP4B version was adapted for use with Parallel Virtual Machine (PVM) on personal computers running the Linux operating system. MCNP, using PVM, can be run on multiple computers simultaneously, offering a factor of speedup roughly the same as the number of computers used. With two 200 MHz Pentium Pro machines, the run time was reduced to forty five minutes, a 1.9 factor of improvement over the single Linux computer. While the time of a single run was greatly reduced, the advantages associated with PVM derive from using computational power not already used. Four possible beams, currently requiring four separate runs, could be run faster when each is individually run on a single machine under Windows NT, rather than using Linux and PVM to run one after another with each multiprocessed across four computers. It would be advantageous, however, to use PVM to distribute the final two beam orientations over four computers.

  17. Dosimetric implications of new compounds for neutron capture therapy (NCT)

    SciTech Connect

    Fairchild, R.G.

    1982-01-01

    Systemic application of radiolabeled or cytotoxic agents should allow targeting of primary and metastatic neoplasms on a cellular level. In fact, drug uptake in non-target cell pools often exceeds toxic levels before sufficient amounts are delivered to tumor. In addition, at the large concentration of molecules necessary for therapy, effects of saturation are often found. Application of NCT can circumvent problems associated with high uptake in competing non-target cell pools, as the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction is activated only within the radiation field. A comparison with other modes of particle therapy indicated that NCT provides significant advantages. It is however, difficult to obtain vehicles for boron transport which demonstrate both the tumor specificity and concentration requisite for NCT. A number of biomolecules have been investigated which show both the necessary concentration and specificity. These include chlorpromazine, thiouracil, porphyrins, amino acids, and nucleosides. However, these analogs have yet to be made available for NCT. Dosimetric implications of binding sites are considered, as well as alternate neutron sources. (ERB)

  18. Computational photography with plenoptic camera and light field capture: tutorial.

    PubMed

    Lam, Edmund Y

    2015-11-01

    Photography is a cornerstone of imaging. Ever since cameras became consumer products more than a century ago, we have witnessed great technological progress in optics and recording mediums, with digital sensors replacing photographic films in most instances. The latest revolution is computational photography, which seeks to make image reconstruction computation an integral part of the image formation process; in this way, there can be new capabilities or better performance in the overall imaging system. A leading effort in this area is called the plenoptic camera, which aims at capturing the light field of an object; proper reconstruction algorithms can then adjust the focus after the image capture. In this tutorial paper, we first illustrate the concept of plenoptic function and light field from the perspective of geometric optics. This is followed by a discussion on early attempts and recent advances in the construction of the plenoptic camera. We will then describe the imaging model and computational algorithms that can reconstruct images at different focus points, using mathematical tools from ray optics and Fourier optics. Last, but not least, we will consider the trade-off in spatial resolution and highlight some research work to increase the spatial resolution of the resulting images.

  19. High-field capture section for SLC positron source

    SciTech Connect

    Hoag, H.A.; Deruyter, H.; Kramer, J.; Yao, C.G.

    1986-05-01

    The positron source for SLC is being installed at the two-thirds point on the SLAC linac. Electron bunches at 33 GeV impinge upon a Tantalum/Tungsten target, producing showers of positrons with energies extending from approximately 2 to 20 MeV, with most positrons at the low end of this range. Positrons with low energies and finite transverse momenta slip phase during the processes of reacceleration and reinjection into the SLC system, increasing the energy spread and reducing the overall yield of the positron source. This reduction in yield has to be minimized by ''capturing'' the positrons with a high-field accelerator section placed as soon after the target as possible. The design, fabrication and RF testing of this accelerator section are described.

  20. Effect of diameter of nanoparticles and capture cross-section library on macroscopic dose enhancement in boron neutron capture therapy

    PubMed Central

    Farhood, Bagher

    2014-01-01

    Purpose The aim of this study is evaluation of the effect of diameter of 10B nanoparticles and various neutron capture cross-section libraries on macroscopic dose enhancement in boron neutron capture therapy (BNCT). Material and methods MCNPX Monte Carlo code was used for simulation of a 252Cf source, a soft tissue phantom and a tumor containing 10B nanoparticles. Using 252Cf as a neutron source, macroscopic dose enhancement factor (MDEF) and total dose rate in tumor in the presence of 100, 200, and 500 ppm of 10B nanoparticles with 25 nm, 50 nm, and 100 nm diameters were calculated. Additionally, the effect of ENDF, JEFF, JENDL, and CENDL neutron capture cross-section libraries on MDEF was evaluated. Results There is not a linear relationship between the average MDEF value and nanoparticles’ diameter but the average MDEF grows with increased concentration of 10B nanoparticles. There is an increasing trend for average MDEF with the tumor distance. The average MDEF values were obtained the same for various neutron capture cross-section libraries. The maximum and minimum doses that effect on the total dose in tumor were neutron and secondary photon doses, respectively. Furthermore, the boron capture related dose component reduced in some extent with increase of diameter of 10B nanoparticles. Conclusions Based on the results of this study, it can be concluded that from physical point of view, various nanoparticle diameters have no dominant effect on average MDEF value in tumor. Furthermore, it is concluded that various neutron capture cross-section libraries are resulted to the same macroscopic dose enhancements. However, it is predicted that taking into account the biological effects for various nanoparticle diameters will result in different dose enhancements. PMID:25834582

  1. Spectromicroscopy of boron for the optimization of boron neutron capture therapy (BNCT) for cancer

    NASA Astrophysics Data System (ADS)

    Gilbert, B.; Redondo, J.; Baudat, P.-A.; Lorusso, G. F.; Andres, R.; Van Meir, E. G.; Brunet, J.-F.; Hamou, M.-F.; Suda, T.; Mercanti, Delio; Ciotti, M. Teresa; Droubay, T. C.; Tonner, B. P.; Perfetti, P.; Margaritondo, M.; DeStasio, Gelsomina

    1998-10-01

    We used synchrotron spectromicroscopy to study the microscopic distribution of boron in rat brain tumour and healthy tissue in the field of boron neutron capture therapy (BNCT). The success of this experimental cancer therapy depends on the preferential uptake of ? in tumour cells after injection of a boron compound (in our case ?, or BSH). With the Mephisto (microscope à emission de photoélectrons par illumination synchrotronique de type onduleur) spectromicroscope, high-magnification imaging and chemical analysis was performed on brain tissue sections from a rat carrying an implanted brain tumour and the results were compared with inductively coupled plasma-atomic emission spectroscopy (ICP-AES) detection of boron in bulk tissue. Boron was found to have been taken up more favourably by regions of tumour rather than healthy tissue, but the resulting boron distribution in the tumour was inhomogeneous. The results demonstrate that Mephisto can perform microchemical analysis of tissue sections, detect and localize the presence of boron with submicron spatial resolution. The application of this technique to boron in brain tissue can therefore be used to evaluate the current efforts to optimize BNC therapy.

  2. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC): application for photodynamic therapy and boron neutron capture therapy.

    PubMed

    Hiramatsu, Ryo; Kawabata, Shinji; Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Ono, Koji; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Hao, Erhong; Vicente, M Graça H

    2015-03-01

    Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days).

  3. Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for Photodynamic Therapy and Boron Neutron Capture Therapy

    PubMed Central

    HIRAMATSU, RYO; KAWABATA, SHINJI; TANAKA, HIROKI; SAKURAI, YOSHINORI; SUZUKI, MINORU; ONO, KOJI; MIYATAKE, SHIN-ICHI; KUROIWA, TOSHIHIKO; HAO, ERHONG; VICENTE, M. GRAÇA H.

    2015-01-01

    Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC’s applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm2) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 1012 n/cm2) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37–43 days). PMID:25546823

  4. Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy.

    PubMed

    Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

    2013-07-01

    Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their (24)Na and (38)Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to (24)Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive (24)Na is mainly generated from (23)Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood (24)Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood (24)Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood (24)Na was determined using a germanium counter. The activity of (24)Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood (24)Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible.

  5. Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy

    PubMed Central

    Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

    2013-01-01

    Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their 24Na and 38Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to 24Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive 24Na is mainly generated from 23Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood 24Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood 24Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood 24Na was determined using a germanium counter. The activity of 24Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood 24Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible. PMID:23392825

  6. Gadolinium as an element for neutron capture therapy

    SciTech Connect

    Brugger, R.M.; Liu, H.B.; Laster, B.H.; Gordon, C.R.; Greenberg, D.D.; Warkentien, L.S.

    1992-12-31

    At BNL, preparations are being made to test in vitro compounds containing Gd and compare their response to the response of GD-DTPA to determine if one or several compounds can be located that enter the cells and enhance the Auger effect. Two similar rotators with positions for cell vials that have been constructed for these tests. The first rotator is made of only paraffin which simulates healthy tissue and provides control curves. The second rotator has 135 ppM of Gd-157 in the paraffin to simulate a Gd loaded tumor. Cells are irradiated in vials in the paraffin rotator and in the Gd-paraffin rotator at the epithermal beam of the Brookhaven Medical Research Reactor (BMRR). This produces an irradiation similar to what a patient would receive In an actual treatment. A combination of irradiations are made with both rotators; with no Gd compound or IdUrd In the cell media, with only Gd compound in the cell media and with both Gd compound and IdUrd in the cell media. The first set shows the effects of gamma rays from the H(n,gamma) reaction and the prompt gamma rays from capture of neutrons by Gd. The second set shows if there is any effect of Gd being in the cell media or inside the cells, i.e., an Auger effect. The third set shows the effect of enhancement by the IdUrd produced by the gamma rays from neutrons captured by either H or Gd. The fourth set combines all of the reactions and enhancements. Preliminary calculations and physical measurements of the doses that the cells will receive In these rotators have been made.

  7. Gadolinium as an element for neutron capture therapy

    SciTech Connect

    Brugger, R.M.; Liu, H.B.; Laster, B.H.; Gordon, C.R.; Greenberg, D.D.; Warkentien, L.S.

    1992-01-01

    At BNL, preparations are being made to test in vitro compounds containing Gd and compare their response to the response of GD-DTPA to determine if one or several compounds can be located that enter the cells and enhance the Auger effect. Two similar rotators with positions for cell vials that have been constructed for these tests. The first rotator is made of only paraffin which simulates healthy tissue and provides control curves. The second rotator has 135 ppM of Gd-157 in the paraffin to simulate a Gd loaded tumor. Cells are irradiated in vials in the paraffin rotator and in the Gd-paraffin rotator at the epithermal beam of the Brookhaven Medical Research Reactor (BMRR). This produces an irradiation similar to what a patient would receive In an actual treatment. A combination of irradiations are made with both rotators; with no Gd compound or IdUrd In the cell media, with only Gd compound in the cell media and with both Gd compound and IdUrd in the cell media. The first set shows the effects of gamma rays from the H(n,gamma) reaction and the prompt gamma rays from capture of neutrons by Gd. The second set shows if there is any effect of Gd being in the cell media or inside the cells, i.e., an Auger effect. The third set shows the effect of enhancement by the IdUrd produced by the gamma rays from neutrons captured by either H or Gd. The fourth set combines all of the reactions and enhancements. Preliminary calculations and physical measurements of the doses that the cells will receive In these rotators have been made.

  8. Commercial Clinical Application of Boron Neutron Capture Therapy

    SciTech Connect

    N /A

    1999-09-03

    CRADA No. 95-CR-09 among the LITCO--now Bechtel BWXT Idaho, LLC; a private company, Neutron Therapies Limited Liability Company, NTL formerly Ionix Corporation; and Washington State University was established in 1996 to further the development of BNCT. NTL has established a laboratory for the synthesis, under US FDA approved current Good Manufacturing Practices (cGMP) guidelines, of key boron intermediates and final boron agents for BNCT. The company has focused initially on the development of the compound GB-10 (Na{sub 2}B{sub 10}H{sub 10}) as the first boron agent of interest. An Investigational New Drug (IND) application for GB-10 has been filed and approved by the FDA for a Phase I human biodistribution trial in patients with non-small cell lung cancer and glioblastoma multiforme at UW under the direction of Professor Keith Stelzer, Principal Investigator (PI). These trials are funded by NTL under a contract with the UW, Department of Radiation Oncology, and the initial phases are nearing completion. Initial results show that boron-10 concentrations on the order of 100 micrograms per gram (100 ppm) can be achieved and maintained in blood with no indication of toxicity.

  9. Thought Field Therapy: A Former Insider's Experience

    ERIC Educational Resources Information Center

    Pignotti, Monica

    2007-01-01

    Thought Field Therapy (TFT) is a novel therapy that employs finger tapping on purported acupressure points. Over the past decade, TFT, promoted on the Internet and through testimonials of fast cures, has gained popularity with therapists, including clinical social workers. Although TFT claims to cure a wide variety of psychological and physical…

  10. A beam-modification assembly for experimental neutron capture therapy of brain tumors

    SciTech Connect

    Slatkin, D.N.; Kalef-Ezra, J.A.; Saraf, S.K.; Joel, D.D.

    1989-01-01

    Recent attempts to treat intracerebral rat gliomas by boron neutron capture therapy (BNCT) have been somewhat disappointing, perhaps in part because of excessive whole-body and nasopharyngeal irradiation. Intracerebral rat gliomas were treated by BNCT with more success using a new beam-modification assembly. 3 refs., 2 figs.

  11. Spermidinium closo-dodecaborate-encapsulating liposomes as efficient boron delivery vehicles for neutron capture therapy.

    PubMed

    Tachikawa, Shoji; Miyoshi, Tatsuro; Koganei, Hayato; El-Zaria, Mohamed E; Viñas, Clara; Suzuki, Minoru; Ono, Koji; Nakamura, Hiroyuki

    2014-10-21

    closo-Dodecaborate-encapsulating liposomes were developed as boron delivery vehicles for neutron capture therapy. The use of spermidinium as a counter cation of closo-dodecaborates was essential not only for the preparation of high boron content liposome solutions but also for efficient boron delivery to tumors.

  12. High-Current Experiments for Accelerator-Based Neutron Capture Therapy Applications

    SciTech Connect

    Gierga, D.P.; Klinkowstein, R.E.; Hughey, B.H.; Shefer, R.E.; Yanch, J.C.; Blackburn, B.W.

    1999-06-06

    Several accelerator-based neutron capture therapy applications are under development. These applications include boron neutron capture therapy for glioblastoma multiform and boron neutron capture synovectomy (BNCS) for rheumatoid arthritis. These modalities use accelerator-based charged-particle reactions to create a suitable neutron source. Neutrons are produced using a high-current, 2-MV terminal tandem accelerator. For these applications to be feasible, high accelerator beam currents must be routinely achievable. An effort was undertaken to explore the operating regime of the accelerator in the milliampere range. In preparation for high-current operation of the accelerator, computer simulations of charged-particle beam optics were performed to establish high-current operating conditions. Herein we describe high beam current simulations and high beam current operation of the accelerator.

  13. Monte Carlo based dosimetry for neutron capture therapy of brain tumors

    NASA Astrophysics Data System (ADS)

    Zaidi, Lilia; Belgaid, Mohamed; Khelifi, Rachid

    2016-11-01

    Boron Neutron Capture Therapy (BNCT) is a biologically targeted, radiation therapy for cancer which combines neutron irradiation with a tumor targeting agent labeled with a boron10 having a high thermal neutron capture cross section. The tumor area is subjected to the neutron irradiation. After a thermal neutron capture, the excited 11B nucleus fissions into an alpha particle and lithium recoil nucleus. The high Linear Energy Transfer (LET) emitted particles deposit their energy in a range of about 10μm, which is of the same order of cell diameter [1], at the same time other reactions due to neutron activation with body component are produced. In-phantom measurement of physical dose distribution is very important for BNCT planning validation. Determination of total absorbed dose requires complex calculations which were carried out using the Monte Carlo MCNP code [2].

  14. Calculation of doublet capture rate for muon capture in deuterium within chiral effective field theory

    NASA Astrophysics Data System (ADS)

    Adam, J.; Tater, M.; Truhlík, E.; Epelbaum, E.; Machleidt, R.; Ricci, P.

    2012-03-01

    The doublet capture rate Λ1 / 2 of the negative muon capture in deuterium is calculated employing the nuclear wave functions generated from accurate nucleon-nucleon (NN) potentials constructed at next-to-next-to-next-to-leading order of heavy-baryon chiral perturbation theory and the weak meson exchange current operator derived within the same formalism. All but one of the low-energy constants that enter the calculation were fixed from pion-nucleon and nucleon-nucleon scattering data. The low-energy constant dˆR (cD), which cannot be determined from the purely two-nucleon data, was extracted recently from the triton β-decay and the binding energies of the three-nucleon systems. The calculated values of Λ1 / 2 show a rather large spread for the used values of the dˆR. Precise measurement of Λ1 / 2 in the future will not only help to constrain the value of dˆR, but also provide a highly nontrivial test of the nuclear chiral EFT framework. Besides, the precise knowledge of the constant dˆR will allow for consistent calculations of other two-nucleon weak processes, such as proton-proton fusion and solar neutrino scattering on deuterons, which are important for astrophysics.

  15. Accelerator Based Neutron Beams for Neutron Capture Therapy

    SciTech Connect

    Yanch, Jacquelyn C.

    2003-04-11

    The DOE-funded accelerator BNCT program at the Massachusetts Institute of Technology has resulted in the only operating accelerator-based epithermal neutron beam facility capable of generating significant dose rates in the world. With five separate beamlines and two different epithermal neutron beam assemblies installed, we are currently capable of treating patients with rheumatoid arthritis in less than 15 minutes (knee joints) or 4 minutes (finger joints) or irradiating patients with shallow brain tumors to a healthy tissue dose of 12.6 Gy in 3.6 hours. The accelerator, designed by Newton scientific Incorporated, is located in dedicated laboratory space that MIT renovated specifically for this project. The Laboratory for Accelerator Beam Applications consists of an accelerator room, a control room, a shielded radiation vault, and additional laboratory space nearby. In addition to the design, construction and characterization of the tandem electrostatic accelerator, this program also resulted in other significant accomplishments. Assemblies for generating epithermal neutron beams were designed, constructed and experimentally evaluated using mixed-field dosimetry techniques. Strategies for target construction and target cooling were implemented and tested. We demonstrated that the method of submerged jet impingement using water as the coolant is capable of handling power densities of up to 6 x 10(sup 7) W/m(sup 2) with heat transfer coefficients of 10(sup 6)W/m(sup 2)-K. Experiments with the liquid metal gallium demonstrated its superiority compared with water with little effect on the neutronic properties of the epithermal beam. Monoenergetic proton beams generated using the accelerator were used to evaluate proton RBE as a function of LET and demonstrated a maximum RBE at approximately 30-40 keV/um, a finding consistent with results published by other researchers. We also developed an experimental approach to biological intercomparison of epithermal beams and

  16. Implications for clinical treatment from the micrometer site dosimetric calculations in boron neutron capture therapy.

    PubMed

    Nichols, Trent L; Kabalka, George W; Miller, Laurence F; McCormack, Michael T; Johnson, Andrew

    2009-07-01

    Boron neutron capture therapy has now been used for several malignancies. Most clinical trials have addressed its use for the treatment of glioblastoma multiforme. A few trials have focused on the treatment of malignant melanoma with brain metastases. Trial results for the treatment of glioblastoma multiforme have been encouraging, but have not achieved the success anticipated. Results of trials for the treatment of malignant melanoma have been very promising, though with too few patients for conclusions to be drawn. Subsequent to these trials, regimens for undifferentiated thyroid carcinoma, hepatic metastases from adenocarcinoma of the colon, and head and neck malignancies have been developed. These tumors have also responded well to boron neutron capture therapy. Glioblastoma is an infiltrative tumor with distant individual tumor cells that might create a mechanism for therapeutic failure though recurrences are often local. The microdosimetry of boron neutron capture therapy can provide an explanation for this observation. Codes written to examine the micrometer scale energy deposition in boron neutron capture therapy have been used to explore the effects of near neighbor cells. Near neighbor cells can contribute a significantly increased dose depending on the geometric relationships. Different geometries demonstrate that tumors which grow by direct extension have a greater near neighbor effect, whereas infiltrative tumors lose this near neighbor dose which can be a significant decrease in dose to the cells that do not achieve optimal boron loading. This understanding helps to explain prior trial results and implies that tumors with small, closely packed cells that grow by direct extension will be the most amenable to boron neutron capture therapy.

  17. Accelerator-based epithermal neutron sources for boron neutron capture therapy of brain tumors.

    PubMed

    Blue, Thomas E; Yanch, Jacquelyn C

    2003-01-01

    This paper reviews the development of low-energy light ion accelerator-based neutron sources (ABNSs) for the treatment of brain tumors through an intact scalp and skull using boron neutron capture therapy (BNCT). A major advantage of an ABNS for BNCT over reactor-based neutron sources is the potential for siting within a hospital. Consequently, light-ion accelerators that are injectors to larger machines in high-energy physics facilities are not considered. An ABNS for BNCT is composed of: (1) the accelerator hardware for producing a high current charged particle beam, (2) an appropriate neutron-producing target and target heat removal system (HRS), and (3) a moderator/reflector assembly to render the flux energy spectrum of neutrons produced in the target suitable for patient irradiation. As a consequence of the efforts of researchers throughout the world, progress has been made on the design, manufacture, and testing of these three major components. Although an ABNS facility has not yet been built that has optimally assembled these three components, the feasibility of clinically useful ABNSs has been clearly established. Both electrostatic and radio frequency linear accelerators of reasonable cost (approximately 1.5 M dollars) appear to be capable of producing charged particle beams, with combinations of accelerated particle energy (a few MeV) and beam currents (approximately 10 mA) that are suitable for a hospital-based ABNS for BNCT. The specific accelerator performance requirements depend upon the charged particle reaction by which neutrons are produced in the target and the clinical requirements for neutron field quality and intensity. The accelerator performance requirements are more demanding for beryllium than for lithium as a target. However, beryllium targets are more easily cooled. The accelerator performance requirements are also more demanding for greater neutron field quality and intensity. Target HRSs that are based on submerged-jet impingement and

  18. An accelerator-based epithermal photoneutron source for boron neutron capture therapy

    SciTech Connect

    Mitchell, Hannah E.

    1996-04-01

    Boron neutron capture therapy is an experimental binary cancer radiotherapy modality in which a boronated pharmaceutical that preferentially accumulates in malignant tissue is first administered, followed by exposing the tissue in the treatment volume to a thermal neutron field. Current usable beams are reactor-based but a viable alternative is the production of an epithermal neutron beam from an accelerator. Current literature cites various proposed accelerator-based designs, most of which are based on proton beams with beryllium or lithium targets. This dissertation examines the efficacy of a novel approach to BNCT treatments that incorporates an electron linear accelerator in the production of a photoneutron source. This source may help to resolve some of the present concerns associated with accelerator sources, including that of target cooling. The photoneutron production process is discussed as a possible alternate source of neutrons for eventual BNCT treatments for cancer. A conceptual design to produce epithermal photoneutrons by high photons (due to bremsstrahlung) impinging on deuterium targets is presented along with computational and experimental neutron production data. A clinically acceptable filtered epithermal neutron flux on the order of 107 neutrons per second per milliampere of electron current is shown to be obtainable. Additionally, the neutron beam is modified and characterized for BNCT applications by employing two unique moderating materials (an Al/AlF3 composite and a stacked Al/Teflon design) at various incident electron energies.

  19. Improvement of dose distribution by central beam shielding in boron neutron capture therapy.

    PubMed

    Sakurai, Yoshinori; Ono, Koji

    2007-12-21

    Since boron neutron capture therapy (BNCT) with epithermal neutron beams started at the Kyoto University Reactor (KUR) in June 2002, nearly 200 BNCT treatments have been carried out. The epithermal neutron irradiation significantly improves the dose distribution, compared with the previous irradiation mainly using thermal neutrons. However, the treatable depth limit still remains. One effective technique to improve the limit is the central shield method. Simulations were performed for the incident neutron energies and the annular components of the neutron source. It was clear that thermal neutron flux distribution could be improved by decreasing the lower energy neutron component and the inner annular component of the incident beam. It was found that a central shield of 4-6 cm diameter and 10 mm thickness is effective for the 12 cm diameter irradiation field. In BNCT at KUR, the depth dose distribution can be much improved by the central shield method, resulting in a relative increase of the dose at 8 cm depth by about 30%. In addition to the depth dose distribution, the depth dose profile is also improved. As the dose rate in the central area is reduced by the additional shielding, the necessary irradiation time, however, increases by about 30% compared to normal treatment.

  20. Boron neutron capture therapy for glioblastoma multiforme: clinical studies in Sweden.

    PubMed

    Capala, Jacek; Stenstam, Britta H; Sköld, Kurt; Munck af Rosenschöld, Per; Giusti, Valerio; Persson, Charlotta; Wallin, Eva; Brun, Arne; Franzen, Lars; Carlsson, Jörgen; Salford, Leif; Ceberg, Crister; Persson, Bertil; Pellettieri, Luigi; Henriksson, Roger

    2003-01-01

    A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radiobiological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol, p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 microg/g (range: 15-32 microg/g) at the time of irradiation (approximately 2-3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0-15.5 Gy(W) and 3.3-6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.

  1. Static and Alternating Field Magnetic Capture and Heating of Iron Oxide Nanoparticles in Simulated Blood Vessels

    NASA Astrophysics Data System (ADS)

    Lee, Joanne Haeun; Shah, Rhythm R.; Brazel, Christopher S.

    2014-11-01

    Targeted drug delivery and localized hyperthermia are being studied as alternatives to conventional cancer treatments, which can affect the whole body and indiscriminately kill healthy cells. Magnetic nanoparticles (MNPs) have potential as drug carriers that can be captured and trigger hyperthermia at the site of the tumor by applying an external magnetic field. This study focuses on comparing the capture efficiency of the magnetic field applied by a static magnet to an alternating current coil. The effect of particle size, degree of dispersion, and the frequency of the AC field on capture and heating were studied using 3 different dispersions: 16 nm maghemite in water, 50 nm maghemite in dopamine, and 20--30 nm magnetite in dimercaptosuccinic acid. A 480G static field captured more MNPs than a similar 480G AC field at either 194 or 428 kHz; however, the AC field also allowed heating. The MNPs in water had a lower capture and heating efficiency than the larger, dopamine-coated MNPs. This finding was supported by dynamic light scattering data showing the particle size distribution and vibrating sample magnetometry data showing that the larger MNPs in the dopamine solution have a higher field of coercivity, exhibit ferrimagnetism and allow for better capture while smaller (16 nm) MNPs exhibit superparamagnetism. The dispersions that captured the best also heated the best. NSF ECE Grant #1358991 supported the first author as an REU student.

  2. Field testing the wildlink capture collar on wolves

    USGS Publications Warehouse

    Mech, L.D.; Gese, E.M.

    1992-01-01

    Seventeen Wildlink capture collars were tested 61 times on 18 gray wolves (Canis lupus) during 1989-1991 in the Superior National Forest of northeastern Minnesota. Overall success rate was 89%, and most failures were attributable to premature battery expiration. When batteries were changed .ltoreq. every 2 months, 17 of 17 tests succeeded. With an upgraded version of the collar in which batteries lasted longer, 17 of 18 tests succeeded. Over the 2-year study, 6 of the 17 collars were lost. For serially recapturing individuals, the Wildlink collar proved useful and reliable if care was taken to replace batteries at proper intervals.

  3. Feasibility of a boron loaded scintillation detector for dose measurements related to boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Kim, Don-Soo; Egan, James J.; Kegel, Gunter H. R.; Desimone, David

    2002-04-01

    The feasibility of the use of a boron loaded scintillation detector in a head phantom for boron neutron capture therapy dose estimates was evaluated. Several monoenergetic neutron groups were produced via the ^7Li(p,n)^7Be reaction in a metallic lithium target using the Van de Graaff accelerator at University of Massachusetts Lowell. The pulse-height spectra were taken from a natural boron loaded (10205-, 304-, 407-, 507-, 570-, 702-, and 780-keV incident neutrons. The results shows that a boron loaded scintillator could be used to distinguish the doses from different radiation sources in boron neutron capture therapy. This detector may be used in the estimation of doses due to fast neutrons, alpha particles and recoil lithium from ^10B(n,α)^7Li, and photons at the same time during neutron irradiation procedures.

  4. Boron analysis and boron imaging in biological materials for Boron Neutron Capture Therapy (BNCT).

    PubMed

    Wittig, Andrea; Michel, Jean; Moss, Raymond L; Stecher-Rasmussen, Finn; Arlinghaus, Heinrich F; Bendel, Peter; Mauri, Pier Luigi; Altieri, Saverio; Hilger, Ralf; Salvadori, Piero A; Menichetti, Luca; Zamenhof, Robert; Sauerwein, Wolfgang A G

    2008-10-01

    Boron Neutron Capture Therapy (BNCT) is based on the ability of the stable isotope 10B to capture neutrons, which leads to a nuclear reaction producing an alpha- and a 7Li-particle, both having a high biological effectiveness and a very short range in tissue, being limited to approximately one cell diameter. This opens the possibility for a highly selective cancer therapy. BNCT strongly depends on the selective uptake of 10B in tumor cells and on its distribution inside the cells. The chemical properties of boron and the need to discriminate different isotopes make the investigation of the concentration and distribution of 10B a challenging task. The most advanced techniques to measure and image boron are described, both invasive and non-invasive. The most promising approach for further investigation will be the complementary use of the different techniques to obtain the information that is mandatory for the future of this innovative treatment modality.

  5. [Development of the method of magnetic neutron capture therapy of cancer].

    PubMed

    Kuznetsov, A A; Podoĭnitsyn, S N; Filippov, V I; Komissarova, L Kh

    2005-01-01

    The method of magnetic neutron capture therapy (MNTC) of cancer can be described as a combination of two methods: the targeted delivery of drugs using magnetic carriers and the proper neutron capture therapy which consists in tumor irradiation with thermal neutrons following the delivery of 10B compounds to the tumor site. Two-component ultradispersed particles containing Fe and C were tested as magnetic adsorbents of boron phenylalanine and borax. The quantities of absorbed borax proved sufficient for high concentration of boron atoms at the tumor site. The kinetics of boron release to saline substantiates the application of Fe-B (10%) ultradispersed particles for efficient MNTC. Both particle types have high magnetization and magnetic homogeneity, can form stable magnetic suspensions, and have low toxicity.

  6. Boron neutron capture therapy as new treatment for clear cell sarcoma: trial on different animal model.

    PubMed

    Andoh, Tooru; Fujimoto, Takuya; Sudo, Tamotsu; Suzuki, Minoru; Sakurai, Yoshinori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Takeuchi, Tamotsu; Sonobe, Hiroshi; Epstein, Alan L; Fukumori, Yoshinobu; Ono, Koji; Ichikawa, Hideki

    2014-06-01

    Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS.

  7. [Possibilities of boron neutron capture therapy in the treatment of malignant brain tumors].

    PubMed

    Kanygin, V V; Kichigin, A I; Gubanova, N V; Taskaev, S Yu

    2015-01-01

    Boron neutron capture therapy (BNCT) that is of the highest attractiveness due to its selective action directly on malignant tumor cells is a promising approach to treating cancers. Clinical interest in BNCT focuses in neuro-oncology on therapy for gliomas, glioblastoma in particular, and BNCT may be used in brain metastatic involvement. This needs an epithermal neutron source that complies with the requirements for BNCT, as well as a 10B-containing agent that will selectively accumulate in tumor tissue. The introduction of BNCT into clinical practice to treat patients with glial tumors will be able to enhance therapeutic efficiency.

  8. NCTPlan application for neutron capture therapy dosimetric planning at MEPhI nuclear research reactor.

    PubMed

    Elyutina, A S; Kiger, W S; Portnov, A A

    2011-12-01

    The results of modeling of two therapeutic beams HEC-1 and HEC-4 at the NRNU "MEPhI" research nuclear reactor exploitable for preclinical treatments are reported. The exact models of the beams are constructed as an input to the NCTPlan code used for planning Neutron Capture Therapy (NCT) procedure. The computations are purposed to improve the accuracy of prediction of a dose absorbed in tissue with the account of all components of radiation.

  9. Power Burst Facility/Boron Neutron Capture Therapy program for cancer treatment, Volume 4, No. 7

    SciTech Connect

    Ackermann, A.L.

    1990-07-01

    This report discusses the monthly progress of the Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNLT) program for cancer treatment. Highlights of the PBF/BNCT Program during July 1990 include progress within the areas of: Gross boron analysis in tissue, blood, and urine; noninvasive boron quantitative determination; analytical radiation transport and interaction modeling for BNCT; large animal model studies; neutron source and facility preparation; administration and common support and PBF operations.

  10. Power Burst Facility/Boron Neutron Capture Therapy Program for cancer treatment

    SciTech Connect

    Ackermann, A.L.; Dorn, R.V. III.

    1990-08-01

    This report discusses monthly progress in the Power Boron Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program for Cancer Treatment. Highlights of the PBF/BNCT Program during August 1990 include progress within the areas of: Gross Boron Analysis in Tissue, Blood, and Urine, boron microscopic (subcellular) analytical development, noninvasive boron quantitative determination, analytical radiation transport and interaction modeling for BNCT, large animal model studies, neutron source and facility preparation, administration and common support and PBF operations.

  11. Tissue composition effect on dose distribution in neutron brachytherapy/neutron capture therapy

    PubMed Central

    Khosroabadi, Mohsen; Farhood, Bagher; Ghorbani, Mahdi; Hamzian, Nima; Moghaddam, Homa Rezaei; Davenport, David

    2016-01-01

    Aim The aim of this study is to assess the effect of the compositions of various soft tissues and tissue-equivalent materials on dose distribution in neutron brachytherapy/neutron capture therapy. Background Neutron brachytherapy and neutron capture therapy are two common radiotherapy modalities. Materials and methods Dose distributions were calculated around a low dose rate 252Cf source located in a spherical phantom with radius of 20.0 cm using the MCNPX code for seven soft tissues and three tissue-equivalent materials. Relative total dose rate, relative neutron dose rate, total dose rate, and neutron dose rate were calculated for each material. These values were determined at various radial distances ranging from 0.3 to 15.0 cm from the source. Results Among the soft tissues and tissue-equivalent materials studied, adipose tissue and plexiglass demonstrated the greatest differences for total dose rate compared to 9-component soft tissue. The difference in dose rate with respect to 9-component soft tissue varied with compositions of the materials and the radial distance from the source. Furthermore, the total dose rate in water was different from that in 9-component soft tissue. Conclusion Taking the same composition for various soft tissues and tissue-equivalent media can lead to error in treatment planning in neutron brachytherapy/neutron capture therapy. Since the International Commission on Radiation Units and Measurements (ICRU) recommends that the total dosimetric uncertainty in dose delivery in radiotherapy should be within ±5%, the compositions of various soft tissues and tissue-equivalent materials should be considered in dose calculation and treatment planning in neutron brachytherapy/neutron capture therapy. PMID:26900352

  12. Lung gene therapy-How to capture illumination from the light already present in the tunnel.

    PubMed

    Xia, Emily; Munegowda, Manjunatha Ankathatti; Cao, Huibi; Hu, Jim

    2014-09-01

    Gene therapy has been considered as the most ideal medical intervention for genetic diseases because it is intended to target the cause of diseases instead of disease symptoms. Availability of techniques for identification of genetic mutations and for in vitro manipulation of genes makes it practical and attractive. After the initial hype in 1990s and later disappointments in clinical trials for more than a decade, light has finally come into the tunnel in recent years, especially in the field of eye gene therapy where it has taken big strides. Clinical trials in gene therapy for retinal degenerative diseases such as Leber's congenital amaurosis (LCA) and choroideremia demonstrated clear therapeutic efficacies without apparent side effects. Although these successful examples are still rare and sporadic in the field, they provide the proof of concept for harnessing the power of gene therapy to treat genetic diseases and to modernize our medication. In addition, those success stories illuminate the path for the development of gene therapy treating other genetic diseases. Because of the differences in target organs and cells, distinct barriers to gene delivery exist in gene therapy for each genetic disease. It is not feasible for authors to review the current development in the entire field. Thus, in this article, we will focus on what we can learn from the current success in gene therapy for retinal degenerative diseases to speed up the gene therapy development for lung diseases, such as cystic fibrosis.

  13. Design of a boron neutron capture enhanced fast neutron therapy assembly

    SciTech Connect

    Wang, Zhonglu

    2006-12-01

    The use of boron neutron capture to boost tumor dose in fast neutron therapy has been investigated at several fast neutron therapy centers worldwide. This treatment is termed boron neutron capture enhanced fast neutron therapy (BNCEFNT). It is a combination of boron neutron capture therapy (BNCT) and fast neutron therapy (FNT). It is believed that BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiform (GBM). A boron neutron capture enhanced fast neutron therapy assembly has been designed for the Fermilab Neutron Therapy Facility (NTF). This assembly uses a tungsten filter and collimator near the patient's head, with a graphite reflector surrounding the head to significantly increase the dose due to boron neutron capture reactions. The assembly was designed using Monte Carlo radiation transport code MCNP version 5 for a standard 20x20 cm2 treatment beam. The calculated boron dose enhancement at 5.7-cm depth in a water-filled head phantom in the assembly with a 5x5 cm2 collimation was 21.9% per 100-ppm 10B for a 5.0-cm tungsten filter and 29.8% for a 8.5-cm tungsten filter. The corresponding dose rate for the 5.0-cm and 8.5-cm thick filters were 0.221 and 0.127 Gy/min, respectively; about 48.5% and 27.9% of the dose rate of the standard 10x10 cm2 fast neutron treatment beam. To validate the design calculations, a simplified BNCEFNT assembly was built using four lead bricks to form a 5x5 cm2 collimator. Five 1.0-cm thick 20x20 cm2 tungsten plates were used to obtain different filter thicknesses and graphite bricks/blocks were used to form a reflector. Measurements of the dose enhancement of the simplified assembly in a water-filled head phantom were performed using a pair of tissue-equivalent ion chambers. One of the ion chambers is loaded with 1000-ppm natural boron (184-ppm 10B) to measure dose due to boron neutron capture. The measured

  14. CT gas lift captures last of field reserves

    SciTech Connect

    Tran, T.B.; Miller, J.; Woodell, M.E.; Johnson, H.

    1996-06-01

    Texaco Exploration and Production Inc.`s (TEPI) Brookeland Field in Newton County, Texas, produces from 30, mostly dual-horizontal, wells in the Austin Chalk reservoir. The wells are typically drilled vertically and casing is set to the top of the Austin Chalk at about 10,000 ft. Building at 15{degree}/100 ft, 4,000-ft laterals are drilled to the northwest and southeast to intersect the natural fractures of the Austin Chalk. The horizontal sections of the wellbore are openhole completions that average 700 b/d of oil and 5 MMcfd of gas. Within 1 year of initial production, the wells require compression to sustain flow and conventional gas lift is used when the wells load up with fluid. Typically, when production declines to 200 Mcfd and 100 b/d of fluid, the gas lift injection point is at 8,000 ft and average gas lift usage is 500 Mcfd. Coiled tubing-conveyed artificial lift was suggested, but first other concerns had to be addressed. The long, horizontal lateral sections functioned as a natural gas and fluid separator, resulting in a distinct slug flow pattern. During a 24-hour period, slug flow caused the wells to produce 100% gas or 100% fluid. For cost reasons TEPI chose conventional, field-installed coiled tubing (CT) gas lift equipment over spoolable equipment. Texaco then formed a team alliance with McMurry-Macco Lift Systems and Dowell to evaluate and complete trial wells with coiled tubing gas lift equipment. This paper reviews the case history of the field, the design considerations of the coiled tubing gas lift, and the surface support equipment used.

  15. Nominal effective radiation doses delivered during clinical trials of boron neutron capture therapy

    SciTech Connect

    Capala, J.; Diaz, A.Z.; Chanana, A.D.

    1997-12-31

    Boron neutron capture therapy (BNCT) is a binary system that, in theory, should selectively deliver lethal, high linear energy transfer (LET) radiation to tumor cells dispersed within normal tissues. It is based on the nuclear reaction 10-B(n, {alpha})7-Li, which occurs when the stable nucleus of boron-10 captures a thermal neutron. Due to the relatively high cross-section of the 10-B nucleus for thermal neutron capture and short ranges of the products of this reaction, tumor cells in the volume exposed to thermal neutrons and containing sufficiently high concentration of 10-B would receive a much higher radiation dose than the normal cells contained within the exposed volume. Nevertheless, radiation dose deposited in normal tissue by gamma and fast neutron contamination of the neutron beam, as well as neutron capture in nitrogen, 14-N(n,p)14-C, hydrogen, 1-H(n,{gamma})2-H, and in boron present in blood and normal cells, limits the dose that can be delivered to tumor cells. It is, therefore, imperative for the success of the BNCT the dosed delivered to normal tissues be accurately determined in order to optimize the irradiation geometry and to limit the volume of normal tissue exposed to thermal neutrons. These are the major objectives of BNCT treatment planning.

  16. Numerical characterization of a tomographic system for online dose measurements in Boron Neutron Capture Therapy

    SciTech Connect

    Minsky, D. M.; Valda, A. A.; Somacal, H.; Burlon, A. A.; Kreiner, A. J.

    2007-02-12

    A tomographic system for online dose measurements in Boron Neutron Capture Therapy (BNCT) based on the measurement of a specific 478 keV {gamma}-ray emitted after the neutron capture in boron is being developed. In the present work we study by means of Monte Carlo numerical simulations the effects of the finite spatial resolution and the limited number of counts, i. e. the statistical noise, on the reconstructed image contrast of numerical phantoms. These phantoms, of simple geometry, mimic the tumor (specific) and the normal tissue (non specific) boron concentrations. The simulated projection data were reconstructed using the expectation-maximization maximum-likelihood algorithm. These studies will help in the improvement of BNCT dosimetry.

  17. Early clinical experience of boron neutron capture therapy for glioblastoma multiforme

    SciTech Connect

    Joel, D.D.; Bergland, R.; Capala, J.

    1995-12-31

    Boron neutron capture therapy (BNCT) is a binary treatment modality that can selectively irradiate tumor tissue. BNCT uses drugs containing a stable isotope of boron. {sup 10}B, to sensitize tumor cells to irradiation by low energy (thermal) neutrons. The interaction of the {sup 10}B with a thermal neutron (neutron capture) causes the {sup 10}B nucleus to split, releasing an alpha particle and a lithium nucleus. These products of the {sup 10}B(n, {alpha}){sup 7}Li reaction are very damaging to cells but have a combined path length in tissue of approximately 14 {mu}m, or roughly the diameter of one or two cells. Thus, most of the ionizing energy imparted to tissue is localized to {sup 10}B-loaded cells.

  18. Boron neutron capture therapy of malignant brain tumors at the Brookhaven Medical Research Reactor

    SciTech Connect

    Joel, D.D.; Coderre, J.A.; Chanana, A.D.

    1996-12-31

    Boron neutron capture therapy (BNCT) is a bimodal form of radiation therapy for cancer. The first component of this treatment is the preferential localization of the stable isotope {sup 10}B in tumor cells by targeting with boronated compounds. The tumor and surrounding tissue is then irradiated with a neutron beam resulting in thermal neutron/{sup 10}B reactions ({sup 10}B(n,{alpha}){sup 7}Li) resulting in the production of localized high LET radiation from alpha and {sup 7}Li particles. These products of the neutron capture reaction are very damaging to cells, but of short range so that the majority of the ionizing energy released is microscopically confined to the vicinity of the boron-containing compound. In principal it should be possible with BNCT to selectively destroy small nests or even single cancer cells located within normal tissue. It follows that the major improvements in this form of radiation therapy are going to come largely from the development of boron compounds with greater tumor selectivity, although there will certainly be advances made in neutron beam quality as well as the possible development of alternative sources of neutron beams, particularly accelerator-based epithermal neutron beams.

  19. Tomographic image of prompt gamma ray from boron neutron capture therapy: A Monte Carlo simulation study

    SciTech Connect

    Yoon, Do-Kun; Jung, Joo-Young; Suk Suh, Tae; Jo Hong, Key

    2014-02-24

    Purpose of paper is to confirm the feasibility of acquisition of three dimensional single photon emission computed tomography image from boron neutron capture therapy using Monte Carlo simulation. Prompt gamma ray (478 keV) was used to reconstruct image with ordered subsets expectation maximization method. From analysis of receiver operating characteristic curve, area under curve values of three boron regions were 0.738, 0.623, and 0.817. The differences between length of centers of two boron regions and distance of maximum count points were 0.3 cm, 1.6 cm, and 1.4 cm.

  20. Drug delivery system design and development for boron neutron capture therapy on cancer treatment.

    PubMed

    Sherlock Huang, Lin-Chiang; Hsieh, Wen-Yuan; Chen, Jiun-Yu; Huang, Su-Chin; Chen, Jen-Kun; Hsu, Ming-Hua

    2014-06-01

    We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,l-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content.

  1. Dose estimation for internal organs during boron neutron capture therapy for body-trunk tumors.

    PubMed

    Sakurai, Y; Tanaka, H; Suzuki, M; Masunaga, S; Kinashi, Y; Kondo, N; Ono, K; Maruhashi, A

    2014-06-01

    Radiation doses during boron neutron capture therapy for body-trunk tumors were estimated for various internal organs, using data from patients treated at Kyoto University Research Reactor Institute. Dose-volume histograms were constructed for tissues of the lung, liver, kidney, pancreas, and bowel. For pleural mesothelioma, the target total dose to the normal lung tissues on the diseased side is 5Gy-Eq in average for the whole lung. It was confirmed that the dose to the liver should be carefully considered in cases of right lung disease.

  2. The formulation of polyhedral boranes for the boron neutron capture therapy of cancer.

    PubMed

    Calabrese, Gianpiero; Nesnas, John J; Barbu, Eugen; Fatouros, Dimitris; Tsibouklis, John

    2012-02-01

    The early promise of boron neutron capture therapy as a method for the treatment of cancer has been inhibited by the inherent toxicity associated with therapeutically useful doses of ¹⁰B-containing pharmacophores, the need for target-tissue specificity and the challenges imposed by biological barriers. Although developments in the synthetic chemistry of polyhedral boranes have addressed issues of toxicity to a considerable extent, the optimisation of the transport and the delivery of boronated agents to the site of action--the subject of this review--is a challenge that is addressed by the development of innovative formulation strategies.

  3. Single step synthesis of nanostructured boron nitride for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Singh, Bikramjeet; Singh, Paviter; Kumar, Manjeet; Thakur, Anup; Kumar, Akshay

    2015-05-01

    Nanostructured Boron Nitride (BN) has been successfully synthesized by carbo-thermic reduction of Boric Acid (H3BO3). This method is a relatively low temperature synthesis route and it can be used for large scale production of nanostructured BN. The synthesized nanoparticles have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and differential thermal analyzer (DTA). XRD analysis confirmed the formation of single phase nanostructured Boron Nitride. SEM analysis showed that the particles are spherical in shape. DTA analysis showed that the phase is stable upto 900 °C and the material can be used for high temperature applications as well boron neutron capture therapy (BNCT).

  4. Monte Carlo calculations of lung dose in ORNL phantom for boron neutron capture therapy.

    PubMed

    Krstic, D; Markovic, V M; Jovanovic, Z; Milenkovic, B; Nikezic, D; Atanackovic, J

    2014-10-01

    Monte Carlo simulations were performed to evaluate dose for possible treatment of cancers by boron neutron capture therapy (BNCT). The computational model of male Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the lung. Calculations have been performed by means of the MCNP5/X code. In this simulation, two opposite neutron beams were considered, in order to obtain uniform neutron flux distribution inside the lung. The obtained results indicate that the lung cancer could be treated by BNCT under the assumptions of calculations.

  5. Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

    PubMed

    Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Fukase, Naomasa; Takeuchi, Tamotsu; Sonobe, Hiroshi; Inoue, Masayoshi; Hirose, Tkanori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Kawamoto, Teruya; Fukumori, Yoshinobu; Yamamoto, Satomi; Atagi, Shinji; Sakurai, Yoshinori; Kurosaka, Masahiro; Ono, Koji; Ichikawa, Hideki; Suzuki, Minoru

    2015-12-01

    Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT.

  6. Tandem-ESQ for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT)

    SciTech Connect

    Kreiner, A. J.; Kwan, J. W.; Henestroza, E.; Burlon, A. A.; Di Paolo, H.; Minsky, D.; Debray, M.; Valda, A.; Somacal, H. R.

    2007-02-12

    A folded tandem, with 1.25 MV terminal voltage, combined with an ElectroStatic Quadrupole (ESQ) chain is being proposed as a machine for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT). The machine is shown to be capable of accelerating a 30 mA proton beam to 2.5 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the on the 7Li(p,n)7Be reaction, to perform BNCT treatment for deep seated tumors in less than an hour.

  7. Experiments to increase the parameters of the vacuum insulation tandem accelerator for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Kasatov, D. A.; Kolesnikov, J. A.; Koshkarev, A. M.; Kuznetsov, A. S.; Makarov, A. N.; Sokolova, E. O.; Sorokin, I. N.; Sycheva, T. V.; Taskaev, S. Yu.; Shchudlo, I. M.

    2016-12-01

    An epithermal neutron source that is based on a vacuum insulation tandem accelerator (VITA) and lithium target was created in the Budker Institute of Nuclear Physics for the development of boron neutron capture therapy (BNCT). A stationary proton beam with 2 MeV energy and 1.6 mA current has been obtained. To carry out BNCT, it is necessary to increase the beam parameters up to 2.3 MeV and 3 mA. Ways to increase the parameters of the proton beam have been proposed and discussed in this paper. The results of the experiments are presented.

  8. Boron neutron capture therapy and radiation synovectomy research at the Massachusetts Institute of Technology Research Reactor

    SciTech Connect

    Zamenhof, R.G.; Nwanguma, C.I.; Wazer, D.E.; Saris, S.; Madoc-Jones, H. ); Sledge, C.B.; Shortkroff, S. )

    1992-04-01

    In this paper, current research in boron neutron capture therapy (BNCT) and radiation synovectomy at the Massachusetts Institute of Technology Research Reactor is reviewed. In the last few years, major emphasis has been placed on the development of BNCT primarily for treatment of brain tumors. This has required a concerted effort in epithermal beam design and construction as well as the development of analytical capabilities for {sup 10}B analysis and patient treatment planning. Prompt gamma analysis and high-resolution track-etch autoradiography have been developed to meet the needs, respectively, for accurate bulk analysis and for quantitative imaging of {sup 10}B in tissue at subcellular resolutions. Monte Carlo-based treatment planning codes have been developed to ensure optimized and individualized patient treatments. In addition, the development of radiation synovectomy as an alternative therapy to surgical intervention is joints that are affected by rheumatoid arthritis is described.

  9. Boron Neutron Capture Therapy (BNCT) Dose Calculation using Geometrical Factors Spherical Interface for Glioblastoma Multiforme

    SciTech Connect

    Zasneda, Sabriani; Widita, Rena

    2010-06-22

    Boron Neutron Capture Therapy (BNCT) is a cancer therapy by utilizing thermal neutron to produce alpha particles and lithium nuclei. The superiority of BNCT is that the radiation effects could be limited only for the tumor cells. BNCT radiation dose depends on the distribution of boron in the tumor. Absorbed dose to the cells from the reaction 10B (n, {alpha}) 7Li was calculated near interface medium containing boron and boron-free region. The method considers the contribution of the alpha particle and recoiled lithium particle to the absorbed dose and the variation of Linear Energy Transfer (LET) charged particles energy. Geometrical factor data of boron distribution for the spherical surface is used to calculate the energy absorbed in the tumor cells, brain and scalp for case Glioblastoma Multiforme. The result shows that the optimal dose in tumor is obtained for boron concentrations of 22.1 mg {sup 10}B/g blood.

  10. Final Stage in the Design of a Boron Neutron Capture Therapy facility at CEADEN, Cuba

    NASA Astrophysics Data System (ADS)

    Cabal, F. Padilla; Martín, G.

    2008-08-01

    A neutron beam simulation study is carried out to determine the most suitable neutron energy for treatment of shallow and deep-seated brain tumors in the context of Boron Neutron Capture Therapy (BNCT). Two figures-of-merit, the therapeutic gain and the neutron fluence are utilized as beam assessment parameters. An irradiation cavity is used instead of a parallel beam port for the therapy. Calculations are performed using the MCNP5 code. After the optimization of our beam-shaper a study of the dose distribution in the head, neck, tyroids, lungs and upper and middle spine had been made. The therapeutic gain is increased while the current required for one hour treatment is decreased in comparison with the trading prototypes of NG used for BNCT

  11. Boron neutron capture therapy for malignant melanoma: first clinical case report in China

    PubMed Central

    Yong, Zhong; Song, Zewen; Zhou, Yongmao; Liu, Tong; Zhang, Zizhu; Zhao, Yanzhong; Chen, Yang; Jin, Congjun; Chen, Xiang; Lu, Jianyun; Han, Rui; Li, Pengzhou; Sun, Xulong; Wang, Guohui; Shi, Guangqing; Zhu, Shaihong

    2016-01-01

    A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals. PMID:28174492

  12. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors

    SciTech Connect

    Soloway, A.H.; Barth, R.F.

    1990-01-01

    Boron neutron capture therapy offers the potentiality for treating brain tumors currently resistant to treatment. The success of this form of therapy is directly dependent upon the delivery of sufficient numbers of thermal-neutrons to tumor cells which possess high concentrations of B-10. The objective of this project is to develop chemical methodology to synthesize boron-containing compounds with the potential for becoming incorporated into rapidly-dividing malignant brain tumor cells and excluded from normal components of the brain and surrounding tissues, to develope biological methods for assessing the potential of the compound by use of cell culture or intratumoral injection, to develop analytical methodology for measuring boron in cells and tissue using direct current plasma atomic emission spectroscopy (DCP-AES) and alpha track autoradiography, to develop biochemical and HPLC procedures for evaluating compound uptake and tissue half-life, and to develop procedures required to assess both in vitro and vivo efficacy of BNCT with selected compounds.

  13. Final Stage in the Design of a Boron Neutron Capture Therapy facility at CEADEN, Cuba

    SciTech Connect

    Cabal, F. Padilla; Martin, G.

    2008-08-11

    A neutron beam simulation study is carried out to determine the most suitable neutron energy for treatment of shallow and deep-seated brain tumors in the context of Boron Neutron Capture Therapy (BNCT). Two figures-of-merit, the therapeutic gain and the neutron fluence are utilized as beam assessment parameters. An irradiation cavity is used instead of a parallel beam port for the therapy. Calculations are performed using the MCNP5 code. After the optimization of our beam-shaper a study of the dose distribution in the head, neck, tyroids, lungs and upper and middle spine had been made. The therapeutic gain is increased while the current required for one hour treatment is decreased in comparison with the trading prototypes of NG used for BNCT.

  14. Neutron dosimetry, moderated energy spectrum, and neutron capture therapy for californium-252 medical sources

    NASA Astrophysics Data System (ADS)

    Rivard, Mark Joseph

    Examination of neutron dosimetry for 252Cf has been conducted using calculative and experimental means. Monte Carlo N-Particle (MCNP) transport code was used in a distributed computing environment as a parallel virtual machine (PVM) to determine the absorbed neutron dose and neutron energy spectrum from 252Cf in a variety of clinically relevant materials. Herein, a Maxwellian spectrum was used to model the 252Cf neutron emissions within these materials. 252Cf mixed-field dosimetry of Applicator Tube (AT) type sources was measured using 1.0 and 0.05 cm3 tissue-equivalent ion chambers and a miniature GM counter. A dosimetry protocol was formulated similar that of ICRU 45. The 252Cf AT neutron dosimetry was determined in the cylindrical coordinate system formalism recommended by the AAPM Task Group 43. These results demonstrated the overwhelming dependence of dosimetry on the source geometry factor as there was no significant neutron attenuation within the source or encapsulation. Gold foils and TLDs were used to measure the thermal flux in the vicinity of 252Cf AT sources to compare with the results calculated using MCNP. As the fast neutron energy spectrum did not markedly changed at increasing distances from the AT source, neutron dosimetry results obtained with paired ion chambers using fixed sensitivity factors agreed well with MCNP results and those in the literature. Calculations of moderated 252Cf neutron energy spectrum with various loadings of 10B and 157Gd were performed, in addition to analysis of neutron capture therapy dosimetry with these isotopes. Radiological concerns such as personnel exposure and shielding of 252Cf emissions were examined. Feasibility of a high specific-activity 252Cf HDR source was investigated through radiochemical and metallurgical studies using stand-ins such as Tb, Gd and 249Cf. Issues such as capsule burst strength due to helium production for a variety of proposed HDR sources were addressed. A recommended 252Cf source

  15. Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy.

    PubMed

    Schaffran, Tanja; Jiang, Nan; Bergmann, Markus; Küstermann, Ekkehard; Süss, Regine; Schubert, Rolf; Wagner, Franz M; Awad, Doaa; Gabel, Detlef

    2014-01-01

    The potential of boron-containing lipids with three different structures, which were intended for use in boron neutron capture therapy, was investigated. All three types of boron lipids contained the anionic dodecaborate cluster as the headgroup. Their effects on two different tumor models in mice following intravenous injection were tested; for this, liposomes with boron lipid, distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing a polyethylene glycol lipid for steric protection, were administered intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell carcinoma and BALB/c mice for CT26/WT colon carcinoma). With the exception of one lipid (B-THF-14), the lipids were well tolerated, and no other animal was lost due to systemic toxicity. The lipid which led to death was not found to be much more toxic in cell culture than the other boron lipids. All of the lipids that were well tolerated showed hemorrhage in both tumor models within a few hours after administration. The hemorrhage could be seen by in vivo magnetic resonance and histology, and was found to occur within a few hours. The degree of hemorrhage depended on the amount of boron administered and on the tumor model. The observed unwanted effect of the lipids precludes their use in boron neutron capture therapy.

  16. Static magnetic field therapy: dosimetry considerations.

    PubMed

    Colbert, Agatha P; Markov, Marko S; Souder, James S

    2008-06-01

    The widespread use of static magnetic field (SMF) therapy as a self-care physical intervention has led to the conduct of numerous randomized controlled trials (RCTs). A recent systematic review of SMF trials for pain reduction concluded that the evidence does not support the use of permanent magnets for pain relief. We argue that this conclusion is unwarranted if the SMF dosage was inadequate or inappropriate for the clinical condition treated. The purpose of this communication is to (1) provide a rationale and an explanation for each of 10 essential SMF dosing parameters that should be considered when conducting trials of SMF therapy, and (2) advocate for the conduct of Phase I studies to optimize SMF dosimetry for each condition prior to implementing a large-scale RCT. A previous critical review of SMF dosimetry in 56 clinical studies found that reporting SMF dosages in a majority of those studies was of such poor quality that the magnetic field exposure at the target tissue could not be characterized. Without knowing what magnetic field actually reached the target, it is impossible to judge dosage adequacy. In order to quantify SMF exposure at the site of pathology (target tissue/s), that site must be clearly named; the distance of the permanent magnet surface from the target must be delineated; the physical parameters of the applied permanent magnet must be described; and the dosing regimen must be precisely reported. If the SMF dosimetry is inadequate, any inferences drawn from reported negative findings are questionable.

  17. Development of JCDS, a computational dosimetry system at JAEA for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Kumada, H.; Yamamoto, K.; Matsumura, A.; Yamamoto, T.; Nakagawa, Y.

    2007-06-01

    Clinical trials of boron neutron capture therapy (BNCT) are being carried out using several research reactors throughout the world. In Japan, many medical groups perform clinical trials of BNCT using Japan Research Reactor No.4 (JRR-4) in Japan Atomic Energy Agency (JAEA). JAEA has developed a treatment planning system, JCDS, in order to evaluate radiation dose given to a patient in the BNCT. JCDS employs a voxel calculation method to compute the radiation dose given to a patient. An initial version of JCDS created a voxel model, dividing a space into 1 × 1 × 1 cm3voxel cells. JCDS was improved to create a detailed voxel model consisting of minute voxel cells such as 2 × 2 × 2 mm3voxel cells. Verification of accuracy of calculations with the detailed voxel mode demonstrated that the detailed voxel model enables JCDS to evaluate more accurately the radiation doses to a patient undergoing BNCT. Furthermore, the calculation code of JCDS is being incorporated into the PHITS system as a Monte-Carlo transport code. By employing the PHITS system in the dose evaluation, total doses given to a patient by combined modality therapy such as BNCT and X-ray therapy can be estimated accurately. Here, an outline and the performances of the latest version of JCDS are presented, and a future system integrated with JCDS is introduced.

  18. Precision calculation for nucleon capture by deuteron with Effective Field Theory

    SciTech Connect

    Bayegan, S.; Sadeghi, H.

    2005-05-06

    We calculate the cross section for radiative capture of neutron by deuteron n + d {yields} 3H+{gamma} using Effective Field Theory (EFT). The calculation includes N2LO order and we compare our results with available calculated data below E = 0.2 MeV.

  19. Design of targeted, capture-based, next generation sequencing tests for precision cancer therapy.

    PubMed

    Hagemann, Ian S; Cottrell, Catherine E; Lockwood, Christina M

    2013-12-01

    In cancer medicine, next generation sequencing (NGS) has emerged as a practical method to generate patient- and tumor-specific genetic data for optimal selection of targeted therapies. Targeted sequencing allows clinical testing to focus on cancer-related genes, thus maximizing the test's sensitivity and specificity for actionable variants. In this review, we summarize the current regulatory environment surrounding clinical NGS, including regulations and professional opinions established by the College of American Pathologists, the Centers for Disease Control and Prevention, the Clinical Laboratory Improvement Amendments, the Clinical and Laboratory Standards Institute, the Association for Molecular Pathology, the New York State Department of Health, and the American College of Medical Genetics. We outline practical considerations for the design of targeted NGS assays, with an emphasis on capture-based methods. Finally, we discuss components of the validation process for clinical NGS assays as well as challenges that still remain for clinical NGS.

  20. Boron analysis for neutron capture therapy using particle-induced gamma-ray emission.

    PubMed

    Nakai, Kei; Yamamoto, Yohei; Okamoto, Emiko; Yamamoto, Tetsuya; Yoshida, Fumiyo; Matsumura, Akira; Yamada, Naoto; Kitamura, Akane; Koka, Masashi; Satoh, Takahiro

    2015-12-01

    The neutron source of BNCT is currently changing from reactor to accelerator, but peripheral facilities such as a dose-planning system and blood boron analysis have still not been established. To evaluate the potential application of particle-induced gamma-ray emission (PIGE) for boron measurement in clinical boron neutron capture therapy, boronophenylalanine dissolved within a cell culture medium was measured using PIGE. PIGE detected 18 μgB/mL f-BPA in the culture medium, and all measurements of any given sample were taken within 20 min. Two hours of f-BPA exposure was required to create a boron distribution image. However, even though boron remained in the cells, the boron on the cell membrane could not be distinguished from the boron in the cytoplasm.

  1. Rational design of gold nanoparticles functionalized with carboranes for application in Boron Neutron Capture Therapy.

    PubMed

    Ciani, Laura; Bortolussi, Silva; Postuma, Ian; Cansolino, Laura; Ferrari, Cinzia; Panza, Luigi; Altieri, Saverio; Ristori, Sandra

    2013-12-31

    In this paper we propose a bottom-up approach to obtain new boron carriers built with ortho-carborane functionalized gold nanoparticles (GNPs) for applications in Boron Neutron Capture Therapy. The interaction between carboranes and the gold surface was assured by one or two SH-groups directly linked to the boron atoms of the B10C2 cage. This allowed obtaining stable, nontoxic systems, though optimal biological performance was hampered by low solubility in aqueous media. To improve cell uptake, the hydrophilic character of carborane functionalized GNPs was enhanced by further coverage with an appropriately tailored diblock copolymer (PEO-b-PCL). This polymer also contained pendant carboranes to provide anchoring to the pre-functionalized GNPs. In vitro tests, carried out on osteosarcoma cells, showed that the final vectors possessed excellent biocompatibility joint to the capacity of concentrating boron atoms in the target, which is encouraging evidenced to pursue applications in vivo.

  2. Optimal Neutron Source & Beam Shaping Assembly for Boron Neutron Capture Therapy

    SciTech Connect

    J. Vujic; E. Greenspan; W.E. Kastenber; Y. Karni; D. Regev; J.M. Verbeke, K.N. Leung; D. Chivers; S. Guess; L. Kim; W. Waldron; Y. Zhu

    2003-04-30

    There were three objectives to this project: (1) The development of the 2-D Swan code for the optimization of the nuclear design of facilities for medical applications of radiation, radiation shields, blankets of accelerator-driven systems, fusion facilities, etc. (2) Identification of the maximum beam quality that can be obtained for Boron Neutron Capture Therapy (BNCT) from different reactor-, and accelerator-based neutron sources. The optimal beam-shaping assembly (BSA) design for each neutron source was also to e obtained. (3) Feasibility assessment of a new neutron source for NCT and other medical and industrial applications. This source consists of a state-of-the-art proton or deuteron accelerator driving and inherently safe, proliferation resistant, small subcritical fission assembly.

  3. Dodecaborate lipid liposomes as new vehicles for boron delivery system of neutron capture therapy.

    PubMed

    Ueno, Manabu; Ban, Hyun Seung; Nakai, Kei; Inomata, Ryu; Kaneda, Yasufumi; Matsumura, Akira; Nakamura, Hiroyuki

    2010-05-01

    Closo-dodecaborate lipid liposomes were developed as new vehicles for boron delivery system (BDS) of neutron capture therapy. The current approach is unique because the liposome shell itself possesses cytocidal potential in combination with neutron irradiation. The liposomes composed of closo-dodecaborate lipids DSBL and DPBL displayed high cytotoxicity with thermal neutron irradiation. The closo-dodecaborate lipid liposomes were taken up into the cytoplasm by endocytosis without degradation of the liposomes. Boron concentration of 22.7 ppm in tumor was achieved by injection with DSBL-25% PEG liposomes at 20mg B/kg. Promising BNCT effects were observed in the mice injected with DSBL-25% PEG liposomes: the tumor growth was significantly suppressed after thermal neutron irradiation (1.8 x 10(12)neutrons/cm(2)).

  4. A Sealed-Accelerator-Tube Neutron Generator for Boron Neutron Capture Therapy Application

    SciTech Connect

    Leung, K.-N.; Leung, K.N.; Lee, Y.; Verbeke, J.M.; Vurjic, J.; Williams, M.D.; Wu, L.K.; Zahir, N.

    1998-06-01

    Radio-frequency (RF) driven ion sources are being developed in Lawrence Berkeley National Laboratory (LBNL) for sealed-accelerator-tube neutron generator applications. By using a 2.5-cm-diameter RF-driven multicusp source and a computer designed 100 keV accelerator column, peak extractable hydrogen current exceeding 1 A from a 3-mm-diameter aperture, together with H{sup +} yields over 94% have been achieved. These experimental findings together with recent moderator design will enable one to develop compact 14 MeV neutron generators based on the D-T fusion reaction. In this new neutron generator, the ion source, the accelerator and the target are all housed in a sealed metal container without pumping. With a 120 keV and 1 A deuteron beam, it is estimated that a treatment time of {approx} 45 minutes is needed for boron neutron capture therapy.

  5. [Development of high boron content liposomes and their promising antitumor effect for neutron capture therapy].

    PubMed

    Nakamura, Hiroyuki

    2013-01-01

      High accumulation and selective delivery of boron into tumor tissue are the most important requirements to achieve the efficient cell-killing effect of boron neutron capture therapy (BNCT) that relies on the nuclear reaction of two essentially nontoxic species, boron-10 ((10)B) and thermal neutrons in boron-loaded tissues. Recent development of boron cluster lipids and their liposomal boron delivery system (BDS) are summarized in this article. Boron compounds that have no affinity to tumor can potentially be delivered to tumor tissues by liposomes, therefore, liposomal BDS would be one of the most attractive approaches for efficient BNCT of various cancers. There are two approaches for BDS: encapsulation of boron compounds into liposomes and incorporation of boron-conjugated lipids into the liposomal bilayer. The combination of both approaches has a potential for reduction of the total dose of liposomes without reducing the efficacy of BNCT.

  6. Carborane-conjugated 2-quinolinecarboxamide ligands of the translocator protein for boron neutron capture therapy.

    PubMed

    Cappelli, Andrea; Valenti, Salvatore; Mancini, Alessandra; Giuliani, Germano; Anzini, Maurizio; Altieri, Saverio; Bortolussi, Silva; Ferrari, Cinzia; Clerici, Anna Maria; Zonta, Cecilia; Carraro, Fabio; Filippi, Irene; Giorgi, Gianluca; Donati, Alessandro; Ristori, Sandra; Vomero, Salvatore; Concas, Alessandra; Biggio, Giovanni

    2010-12-15

    Potential boron neutron capture therapy (BNCT) agents have been designed on the basis of the evidence about translocator protein (TSPO) overexpression on the outer mitochondrial membrane of tumor cells. The structure of the first TSPO ligand bearing a carborane cage (compound 2d) has been modified in order to find a suitable candidate for in vivo studies. The designed compounds were synthesized and evaluated for their potential interaction with TSPO and tumor cells. In vitro biological evaluation showed in the case of fluoromethyl derivative 4b a nanomolar TSPO affinity very similar to that of 2d, a significantly lower cytotoxicity, and a slightly superior performance as boron carrier toward breast cancer cells. Moreover, compound 4b could be used as a ¹⁹F magnetic resonance imaging (MRI) agent as well as labeled with ¹¹C or ¹⁸F to obtain positron emission tomography (PET) radiotracers in order to apply the "see and treat" strategy in BNCT.

  7. Cell cycle dependence of boron uptake from two boron compounds used for clinical neutron capture therapy.

    PubMed

    Yoshida, F; Matsumura, A; Shibata, Y; Yamamoto, T; Nakauchi, H; Okumura, M; Nose, T

    2002-12-10

    In neutron capture therapy, it is important that the boron is selectively uptaken by tumor cells. In the present study, we used flow cytometry to sort the cells in the G0/G1 phase and those in the G2/M phase, and the boron concentration in each fraction was measured with inductively coupled plasma atomic emission spectroscopy. The results revealed that sodium borocaptate and boronophenylalanine (BPA), were associated with higher rates of boron uptake in the G2/M than in the G0/G1 phase. However, the difference was more prominent in the case of BPA. The G2/M:G0/G1 ratio decreased as a function of exposure time in BPA containing culture medium, thereby indicating the cell cycle dependency of BPA uptake. Such heterogeneity of boron uptake by tumor cells should be considered for microdosimetry.

  8. Hybrid data capture for monitoring patients on highly active antiretroviral therapy (HAART) in urban Botswana.

    PubMed Central

    Bussmann, Hermann; Wester, C. William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G.

    2006-01-01

    Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care. PMID:16501730

  9. Single step synthesis of nanostructured boron nitride for boron neutron capture therapy

    SciTech Connect

    Singh, Bikramjeet; Singh, Paviter; Kumar, Akshay; Kumar, Manjeet; Thakur, Anup

    2015-05-15

    Nanostructured Boron Nitride (BN) has been successfully synthesized by carbo-thermic reduction of Boric Acid (H{sub 3}BO{sub 3}). This method is a relatively low temperature synthesis route and it can be used for large scale production of nanostructured BN. The synthesized nanoparticles have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and differential thermal analyzer (DTA). XRD analysis confirmed the formation of single phase nanostructured Boron Nitride. SEM analysis showed that the particles are spherical in shape. DTA analysis showed that the phase is stable upto 900 °C and the material can be used for high temperature applications as well boron neutron capture therapy (BNCT)

  10. Boron neutron capture therapy of ocular melanoma and intracranial glioma using p-boronophenylalanine

    SciTech Connect

    Coderre, J.A.; Greenberg, D.; Micca, P.L.; Joel, D.D.; Saraf, S. ); Packer, S. . Div. of Ophthalmology)

    1990-01-01

    During conventional radiotherapy, the dose that can be delivered to the tumor is limited by the tolerance of the surrounding normal tissue within the treatment volume. Boron Neutron Capture Therapy (BNCT) represents a promising modality for selective tumor irradiation. The key to effective BNCT is selective localization of {sup 10}B in the tumor. We have shown that the synthetic amino acid p-boronophenylalanine (BPA) will selectively deliver boron to melanomas and other tumors such as gliosarcomas and mammary carcinomas. Systemically delivered BPA may have general utility as a boron delivery agent for BNCT. In this paper, BNCT with BPA is used in treatment of experimentally induced gliosarcoma in rats and nonpigmented melanoma in rabbits. The tissue distribution of boron is described, as is response to the BNCT. 6 refs., 4 figs., 1 tab.

  11. Combination of boron and gadolinium compounds for neutron capture therapy. An in vitro study.

    PubMed

    Matsumura, A; Zhang, T; Nakai, K; Endo, K; Kumada, H; Yamamoto, T; Yoshida, F; Sakurai, Y; Yamamoto, K; Nose, T

    2005-03-01

    In neutron capture therapy, the therapeutic effect of the boron compound is based on alpha particles produced by the B(n, alpha) reaction while with the gadolinium compound the main radiation effect is from gamma rays derived from the Gd(n, gamma) reaction. The uptake and distribution within the tumor may be different among these compounds. Thus, the combination of the boron and gadolinium compounds may be beneficial for enhancing the radiation dose to the tumor. Chinese hamster fibroblast V79 cells were used. For the neutron targeting compounds, 10B (BSH) at 0, 5, 10, and 15 ppm, and 157Gd (Gd-BOPTA) at 0, 800, 1600, 2400, 3200, and 4800 ppm, were combined. The neutron irradiation was performed with thermal neutrons for 30 min. (neutron flux: 0.84 x 10(8) n/cm2/s in free air). The combination of the boron and gadolinium compounds showed an additive effect when the gadolinium concentration was lower than 1600 ppm. This additive effect decreased as a function of gadolinium concentration at 2400 ppm and resulted in no additive effect at more than 3200 ppm of gadolinium. In conclusion, the combination of the boron and gadolinium compounds can enhance the therapeutic effect with an optimum concentration ratio. When the gadolinium concentration is too high, it may weaken the boron neutron capture reaction due to the high cross-section of gadolinium compound against neutrons.

  12. Preliminary treatment planning and dosimetry for a clinical trial of neutron capture therapy using a fission converter epithermal neutron beam.

    PubMed

    Kiger, W S; Lu, X Q; Harling, O K; Riley, K J; Binns, P J; Kaplan, J; Patel, H; Zamenhof, R G; Shibata, Y; Kaplan, I D; Busse, P M; Palmer, M R

    2004-11-01

    A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard-MIT using a fission converter epithermal neutron beam. This epithermal neutron beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.0 g/m(2) body surface area over 90 min followed by irradiation with epithermal neutrons. Treatments were planned using NCTPlan and an accelerated version of the Monte Carlo radiation transport code MCNP 4B. Treatments were delivered in two fractions with two or three fields. Field order was reversed between fractions to equalize the average blood boron concentration between fields. The initial dose in the dose escalation study was 7.0 RBEGy, prescribed as the mean dose to the whole brain volume. This prescription dose was increased by 10% to 7.7 RBEGy in the second cohort of patients. A pharmacokinetic model was used to predict the blood boron concentration for determination of the required beam monitor units with good accuracy; differences between prescribed and delivered doses were 1.5% or less. Estimates of average tumor doses ranged from 33.7 to 83.4 RBEGy (median 57.8 RBEGy), a substantial improvement over our previous trial where the median value of the average tumor dose was 25.8 RBEGy.

  13. DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV.

    PubMed

    Kondo, Natsuko; Sakurai, Yoshinori; Hirota, Yuki; Tanaka, Hiroki; Watanabe, Tsubasa; Nakagawa, Yosuke; Narabayashi, Masaru; Kinashi, Yuko; Miyatake, Shin-ichi; Hasegawa, Masatoshi; Suzuki, Minoru; Masunaga, Shin-ichiro; Ohnishi, Takeo; Ono, Koji

    2016-03-01

    Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4-/- p53-/- and Lig4+/+ p53-/- to irradiation using a thermal neutron beam in the presence or absence of (10)B-para-boronophenylalanine (BPA). The Lig4-/- p53-/- cell line had a higher sensitivity than the Lig4+/+ p53-/-cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that (10)B uptake was higher in the Lig4+/+ p53-/- than in the Lig4-/- p53-/- cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.

  14. Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head and Neck Cancer

    SciTech Connect

    Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna; Saarilahti, Kauko; Atula, Timo; Collan, Juhani; Salli, Eero; Kortesniemi, Mika; Uusi-Simola, Jouni; Maekitie, Antti; Seppaenen, Marko; Minn, Heikki; Kotiluoto, Petri; Auterinen, Iiro; Savolainen, Sauli; Kouri, Mauri; Joensuu, Heikki

    2007-10-01

    Purpose: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. Methods and Materials: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria and adverse effects using the National Cancer Institute common toxicity grading v3.0. Intravenously administered boronophenylalanine-fructose (BPA-F, 400 mg/kg) was used as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Ten patients received BNCT twice; 2 were treated once. Ten (83%) patients responded to BNCT, and 2 (17%) had tumor growth stabilization for 5.5 and 7.6 months. The median duration of response was 12.1 months; six responses were ongoing at the time of analysis or death (range, 4.9-19.2 months). Four (33%) patients were alive without recurrence with a median follow-up of 14.0 months (range, 12.8-19.2 months). The most common acute adverse effects were mucositis, fatigue, and local pain; 2 patients had a severe (Grade 3) late adverse effect (xerostomia, 1; dysphagia, 1). Conclusions: Boron neutron capture therapy is effective and safe in the treatment of inoperable, locally advanced head and neck carcinomas that recur at previously irradiated sites.

  15. Electronic data capture platform for clinical research based on mobile phones and near field communication technology.

    PubMed

    Morak, Jürgen; Schwetz, Verena; Hayn, Dieter; Fruhwald, Friedrich; Schreier, Gunter

    2008-01-01

    Electronic data capture systems support data acquisition for clinical research and enable the evaluation of new investigational medical devices. In case of evaluating a device the most challenging part is the user interface i.e. the solution how to acquire the data within a clinical setting and to synchronize them with a web-based data centre. The aim of this paper is to describe the development of an electronic data capture system with a mobile data input solution based on mobile phones and Near Field Communication technology. This system was evaluated within a real clinical setting and demonstrated high usability, security and reliability.

  16. A new analytical formula for neutron capture gamma dose calculations in double-bend mazes in radiation therapy

    PubMed Central

    Ghiasi, Hosein; Mesbahi, Asghar

    2012-01-01

    Background Photoneutrons are produced in radiation therapy with high energy photons. Also, capture gamma rays are the byproduct of neutrons interactions with wall material of radiotherapy rooms. Aim In the current study an analytical formula was proposed for capture gamma dose calculations in double bend mazes in radiation therapy rooms. Materials and methods A total of 40 different layouts with double-bend mazes and a 18 MeV photon beam of Varian 2100 Clinac were simulated using MCNPX Monte Carlo (MC) code. Neutron capture gamma ray dose equivalent was calculated by the MC method along the maze and at the maze entrance door of all the simulated rooms. Then, all MC resulted data were fitted to an empirical formula for capture gamma dose calculations. Wu–McGinley analytical formula for capture gamma dose equivalent at the maze entrance door in single-bend mazes was also used for comparison purposes. Results For capture gamma dose equivalents at the maze entrance door, the difference of 2–11% was seen between MC and the derived equation, while the difference of 36–87% was found between MC and the Wu–McGinley methods. Conclusion Our results showed that the derived formula results were consistent with the MC results for all of 40 different geometries. However, as a new formula, further evaluations are required to validate its use in practical situations. Finally, its application is recommend for capture gamma dose calculations in double-bend mazes to improve shielding calculations. PMID:24377027

  17. Epithermal neutron beams from the 7 Li(p,n) reaction near the threshold for neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Porras, I.; Praena, J.; Arias de Saavedra, F.; Pedrosa, M.; Esquinas, P.; L. Jiménez-Bonilla, P.

    2016-11-01

    Two applications for neutron capture therapy of epithermal neutron beams calculated from the 7Li ( p , n reaction are discussed. In particular, i) for a proton beam of 1920 keV of a 30 mA, a neutron beam of adequate features for BNCT is found at an angle of 80° from the forward direction; and ii) for a proton beam of 1910 keV, a neutron beam is obtained at the forward direction suitable for performing radiobiology experiments for the determination of the biological weighting factors of the fast dose component in neutron capture therapy.

  18. Characteristics of a heavy water photoneutron source in boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Danial, Salehi; Dariush, Sardari; M. Salehi, Jozani

    2013-07-01

    Bremsstrahlung photon beams produced by medical linear accelerators are currently the most commonly used method of radiation therapy for cancerous tumors. Photons with energies greater than 8-10 MeV potentially generate neutrons through photonuclear interactions in the accelerator's treatment head, patient's body, and treatment room ambient. Electrons impinging on a heavy target generate a cascade shower of bremsstrahlung photons, the energy spectrum of which shows an end point equal to the electron beam energy. By varying the target thickness, an optimum thickness exists for which, at the given electron energy, maximum photon flux is achievable. If a source of high-energy photons i.e. bremsstrahlung, is conveniently directed to a suitable D2O target, a novel approach for production of an acceptable flux of filterable photoneturons for boron neutron capture therapy (BNCT) application is possible. This study consists of two parts. 1. Comparison and assessment of deuterium photonuclear cross section data. 2. Evaluation of the heavy water photonuclear source.

  19. Potential of using boric acid as a boron drug for boron neutron capture therapy for osteosarcoma.

    PubMed

    Hsu, C F; Lin, S Y; Peir, J J; Liao, J W; Lin, Y C; Chou, F I

    2011-12-01

    Osteosarcoma is a malignant tumor commonly found in human and animals. The ability of boric acid (BA) to accumulate in osteosarcoma due to the mechanism of the bone formation of cancer cells would make boron neutron capture therapy (BNCT) an alternative therapy for osteosarcoma. This study evaluated the feasibility of using BA as the boron drug for BNCT of bone cancer. The cytotoxicity of BA to L929 cells exceeded that of UMR-106 cells. With 25 μg (10)B/mL medium of BA treatment, the boron concentration in UMR-106 cells was higher than that in L929 cells. The biodistribution and pharmacokinetics of BA in Sprague-Dawley (SD) rats were studied by administrating 25 mg (10)B/kg body weight to SD rats. Blood boron level decreased rapidly within one hour after BA injection. Boron concentration in the long bone was 4-6 time higher than that of blood. Results of this study suggest that BA may be a potential drug for BNCT for osteosarcoma.

  20. Design of a californium-based epithermal neutron beam for neutron capture therapy.

    PubMed

    Yanch, J C; Kim, J K; Wilson, M J

    1993-08-01

    The potential of the spontaneously fissioning isotope, 252Cf, to provide epithermal neutrons for use in boron neutron capture therapy (BNCT) has been investigated using Monte Carlo simulation. The Monte Carlo code MCNP was used to design an assembly composed of a 26 cm long, 11 cm radius cylindrical D2O moderator followed by a 64 cm long Al filter. Lithium filters are placed between the moderator and the filter and between the Al and the patient. A reflector surrounding the moderator/filter assembly is required in order to maintain adequate therapy flux at the patient position. An ellipsoidal phantom composed of skull- and brain-equivalent material was used to determine the dosimetric effect of this beam. It was found that both advantage depths and advantage ratios compare very favourably with reactor and accelerator epithermal neutron sources. The dose rate obtainable, on the other hand, is 4.1 RBE cGy min-1, based on a very large (1.0 g) source of 252Cf. This dose rate is two to five times lower than those provided by existing reactor beams and can be viewed as a drawback of using 252Cf as a neutron source. Radioisotope sources, however, do offer the advantage of in-hospital installation.

  1. Studies on depth-dose-distribution controls by deuteration and void formation in boron neutron capture therapy.

    PubMed

    Sakurai, Yoshinori

    2004-08-07

    Physical studies on (i) replacement of heavy water for body water (deuteration), and (ii) formation of a void in human body (void formation) were performed as control techniques for dose distribution in a human head under neutron capture therapy. Simulation calculations were performed for a human-head-size cylindrical phantom using a two-dimensional transport calculation code for mono-energetic incidences of higher-energy epi-thermal neutrons (1.2-10 keV), lower-energy epi-thermal neutrons (3.1-23 eV) and thermal neutrons (1 meV to 0.5 eV). The deuteration was confirmed to be effective both in thermal neutron incidence and in epi-thermal neutron incidence from the viewpoints of improvement of the thermal neutron flux distribution and elimination of the secondary gamma rays. For the void formation, a void was assumed to be 4 cm in diameter and 3 cm in depth at the surface part in this study. It was confirmed that the treatable depth was improved almost 2 cm for any incident neutron energy in the case of the 10 cm irradiation field diameter. It was made clear that the improvement effect was larger in isotropic incidence than in parallel incidence, in the case that an irradiation field size was delimited fitting into a void diameter.

  2. Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound

    SciTech Connect

    Mishima, Y.; Ichihashi, M.; Tsuji, M.; Hatta, S.; Ueda, M.; Honda, C.; Suzuki, T.

    1989-05-01

    As pigment cells undergo melanoma genesis, accentuated melanogenesis concurrently occurs in principle. Subsequent to the understanding of intrinsic factors controlling both processes, we found our selective melanoma neutron capture therapy (NCT) using 10B-dopa (melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA), followed by 10B(n, alpha)7Li reaction, induced by essentially harmless thermal neutrons, which releases energy of 2.33 MeV to 14 mu, the diameter of melanoma cells. In vitro/in vivo radiobiological analysis revealed the highly enhanced melanoma killing effect of 10B1-BPA. Chemical and prompt gamma ray spectrometry assays of 10B accumulated within melanoma cells after 10B1-BPA administration in vitro and in vivo show high affinity, e.g., 10B melanoma/blood ratio of 11.5. After successfully eradicating melanoma transplanted into hamsters with NCT, we advanced to preclinical studies using spontaneously occurring melanoma in Duroc pig skin. We cured three melanoma cases, 4.6 to 12 cm in diameter, by single neutron capture treatment. Complete disappearance of melanoma was obtained without substantial side effects. Acute and subacute toxicity as well as pharmacodynamics of 10B1-BPA have been studied in relation to therapeutic dosage requirements. Clinical radiation dosimetry using human phantom has been carried out. Further preclinical studies using human melanoma transplanted into nude mouse have been a useful model for obtaining optimal results for each melanoma type. We recently treated the first human melanoma patient with our NCT, using essentially the method for Duroc pig melanoma, and obtained similar regression time course leading to cure.

  3. Clinical potential of boron neutron capture therapy for locally recurrent inoperable previously irradiated head and neck cancer.

    PubMed

    Lim, Diana; Quah, Daniel S C; Leech, Michelle; Marignol, Laure

    2015-12-01

    This review compares the safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of previously irradiated, inoperable locoregional recurrent HNC patients and compares BNCT against the standard treatment of platinum-based chemotherapy. Our analysis of published clinical trials highlights efficacy of BNCT associated with mild side effects. However, the use of BNCT should be explored in stratified randomised trials.

  4. Laboratory and Field Age of Aqueous Grape Juice Bait and Capture of Zaprionus indianus (Diptera: Drosophilidae).

    PubMed

    Epsky, Nancy D; Gill, Micah A

    2017-03-08

    Volatile chemicals produced by actively fermenting aqueous grape juice bait have been found to be highly attractive to the African fig fly, Zaprionus indianus Gupta. This is a highly dynamic system and time period of fermentation is an important factor in bait efficacy. A series of field tests were conducted that evaluated effects of laboratory versus field fermentation and sampling period (days after placement [DAP]) on bait effectiveness as the first step in identifying the chemicals responsible for attraction. Tests of traps with bait that had been aged in the laboratory for 0, 3, 6, and 9 d and then sampled 3 DAP found higher capture in traps with 0- and 3-d-old baits than in traps with 6- or 9-d-old baits. To further define the time period that produced the most attractive baits, a subsequent test evaluated baits aged for 0, 2, 4, and 6 d in the laboratory and sampled after 1-4 DAP, with traps sampled and bait discarded at the end of each DAP period. The highest capture was in traps with 4-d-old bait sampled 1 DAP, with the second best capture in traps with 0-d-old bait sampled 3 DAP. However, there tended to be fewer flies as DAP increased, indicating potential loss of identifiable flies owing to decomposition in the actively fermenting solutions. When traps were sampled and bait recycled daily, the highest capture was in 2- and 4-d-old baits sampled 1 DAP and in 0-d-old baits sampled 2-4 DAP. Similar patterns were observed for capture of nontarget drosophilids.

  5. Convection enhanced delivery of carboranylporphyrins for neutron capture therapy of brain tumors.

    PubMed

    Kawabata, Shinji; Yang, Weilian; Barth, Rolf F; Wu, Gong; Huo, Tianyao; Binns, Peter J; Riley, Kent J; Ongayi, Owendi; Gottumukkala, Vijay; Vicente, M Graça H

    2011-06-01

    Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive 10B is irradiated with low energy thermal neutrons to produce α-particles (10B[n,α] Li). Carboranylporphyrins are a class of substituted porphyrins containing multiple carborane clusters. Three of these compounds, designated H2TBP, H2TCP, and H2DCP, have been evaluated in the present study. The goals were two-fold. First, to determine their biodistribution following intracerebral (i.c.) administration by short term (30 min) convection enhanced delivery (CED) or sustained delivery over 24 h by Alzet™ osmotic pumps to F98 glioma bearing rats. Second, to determine the efficacy of H2TCP and H2TBP as boron delivery agents for BNCT in F98 glioma bearing rats. Tumor boron concentrations immediately after i.c. pump delivery were high and they remained so at 24 h. The corresponding normal brain concentrations were low and the blood and liver concentrations were undetectable. Based on these data, therapy studies were initiated at the Massachusetts Institute of Technology (MIT) Research Reactor (MITR) with H2TCP and H2TBP 24 h after CED or pump delivery. Mean survival times (MST) ± standard deviations of animals that had received H2TCP or H2TBP, followed by BNCT, were of 35 ± 4 and 44 ± 10 days, compared to 23 ± 3 and 27 ± 3 days, respectively, for untreated and irradiated controls. However, since the tumor boron concentrations of the carboranylporphyrins were 3-5× higher than intravenous (i.v.) boronophenylalanine (BPA), we had expected that the MSTs would have been greater. Histopathologic examination of brains of BNCT treated rats revealed that there were large numbers of porphyrin-laden macrophages, as well as extracellular accumulations of porphyrins, indicating that the seemingly high tumor boron concentrations did not represent the true tumor cellular uptake. Nevertheless, our data are the first to show that carboranyl porphyrins can be

  6. The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model

    PubMed Central

    Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

    2015-01-01

    Purpose Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa. PMID:26325195

  7. Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential.

    PubMed

    Sköld, K; Gorlia, T; Pellettieri, L; Giusti, V; H-Stenstam, B; Hopewell, J W

    2010-07-01

    The purpose of this study was to assess the potential of boron neutron capture therapy (BNCT), with a 6-h infusion of the boron carrier l-boronophenylalanine as a fructose preparation (BPA-f), as first-line radiotherapy for newly diagnosed glioblastoma multiforme (GBM). Patient survival data from a Phase II study using BNCT were compared with retrospective data from the two arms of a Phase III study using conventional radiotherapy (RT) in the reference arm and using RT plus concomitant and adjuvant medication with temozolomide (TMZ) in the experimental arm, and were also compared with small subgroups of these patients for whom the methylation status of the MGMT (O(6)-methylguanine-DNA methyltransferase) DNA repair gene was known. Differences in the baseline characteristics, salvage therapy after recurrence and levels of severe adverse events were also considered. The results indicate that BNCT offers a treatment that is at least as effective as conventional RT alone. For patients with an unmethylated MGMT DNA repair gene, a possible clinical advantage of BNCT over RT/TMZ was suggested. BNCT is a single-day treatment, which is of convenience to patients, with mild side effects, which would offer an initial 6 weeks of good-quality life during the time when patients would otherwise be undergoing daily treatments with RT and TMZ. It is suggested that the use of BNCT with a 6-h infusion of BPA-f should be explored in a stratified randomised Phase II trial in which patients with the unmethylated MGMT DNA repair gene are offered BNCT in the experimental arm and RT plus TMZ in the reference arm.

  8. Capture and emission of electrons in quantum wells under applied electric field

    NASA Astrophysics Data System (ADS)

    Vinter, B.; Luc, F.; Bois, P.; Thibaudeau, L.; Rosencher, E.

    1994-06-01

    Important characteristics of Quantum Well Infrared Photodetectors are determined almost entirely by the photoionization rate of electrons out of the Quantum Well (QW) and the recapture into the QWs. To elucidate these processes microscopically we have made structures in which the QWs are isolated from one contact by a completely blocking barrier, so that the steady state current vanishes. The transient current induced by photoionization out of the QWs gives a direct measurement of the photoionization cross section and the escape probability of a photoexcited electron. We have found that the variation of the latter with the electric field may be described by a simple barrier lowering model combined with statistical fluctuation of the QW width. The capture process has been studied by impedance spectroscopy in samples containing only one well. The capture velocity thus measured is found to decrease with increasing applied electric field but within experimental uncertainties it does not depend on the width of the well for well widths between 3 and 7.5 nm. Theoretical results on optical phonon mediated transitions in the applied field from barrier to well states show a generally good agreement with experiment at low fields but less dependence on the field.

  9. Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy

    NASA Astrophysics Data System (ADS)

    Singh, Bikramjeet; Kaur, Gurpreet; Singh, Paviter; Singh, Kulwinder; Kumar, Baban; Vij, Ankush; Kumar, Manjeet; Bala, Rajni; Meena, Ramovatar; Singh, Ajay; Thakur, Anup; Kumar, Akshay

    2016-10-01

    Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT.

  10. Dynamic infrared imaging for biological and medical applications in Boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Santa Cruz, Gustavo A.; González, Sara J.; Dagrosa, Alejandra; Schwint, Amanda E.; Carpano, Marina; Trivillin, Verónica A.; Boggio, Esteban F.; Bertotti, José; Marín, Julio; Monti Hughes, Andrea; Molinari, Ana J.; Albero, Miguel

    2011-05-01

    Boron Neutron Capture Therapy (BNCT) is a treatment modality, currently focused on the treatment of cancer, which involves a tumor selective 10B compound and a specially tuned neutron beam to produce a lethal nuclear reaction. BNCT kills target cells with microscopic selectivity while sparing normal tissues from potentially lethal doses of radiation. In the context of the Argentine clinical and research BNCT projects at the National Atomic Energy Commission and in a strong collaboration with INVAP SE, we successfully implemented Dynamic Infrared Imaging (DIRI) in the clinical setting for the observation of cutaneous melanoma patients and included DIRI as a non invasive methodology in several research protocols involving small animals. We were able to characterize melanoma lesions in terms of temperature and temperature rate-of-recovery after applying a mild cold thermal stress, distinguishing melanoma from other skin pigmented lesions. We observed a spatial and temporal correlation between skin acute reactions after irradiation, the temperature pattern and the dose distribution. We studied temperature distribution as a function of tumor growth in mouse xenografts, observing a significant correlation between tumor temperature and drug uptake; we investigated temperature evolution in the limbs of Wistar rats for a protocol of induced rheumatoid arthritis (RA), DIRI being especially sensitive to RA induction even before the development of clinical signs and studied surface characteristics of tumors, precancerous and normal tissues in a model of oral cancer in the hamster cheek pouch.

  11. Verification of the computational dosimetry system in JAERI (JCDS) for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Kumada, H.; Yamamoto, K.; Matsumura, A.; Yamamoto, T.; Nakagawa, Y.; Nakai, K.; Kageji, T.

    2004-08-01

    Clinical trials for boron neutron capture therapy (BNCT) by using the medical irradiation facility installed in Japan Research Reactor No. 4 (JRR-4) at Japan Atomic Energy Research Institute (JAERI) have been performed since 1999. To carry out the BNCT procedure based on proper treatment planning and its precise implementation, the JAERI computational dosimetry system (JCDS) which is applicable to dose planning has been developed in JAERI. The aim of this study was to verify the performance of JCDS. The experimental data with a cylindrical water phantom were compared with the calculation results using JCDS. Data of measurements obtained from IOBNCT cases at JRR-4 were also compared with retrospective evaluation data with JCDS. In comparison with phantom experiments, the calculations and the measurements for thermal neutron flux and gamma-ray dose were in a good agreement, except at the surface of the phantom. Against the measurements of clinical cases, the discrepancy of JCDS's calculations was approximately 10%. These basic and clinical verifications demonstrated that JCDS has enough performance for the BNCT dosimetry. Further investigations are recommended for precise dose distribution and faster calculation environment.

  12. GPU-based prompt gamma ray imaging from boron neutron capture therapy

    SciTech Connect

    Yoon, Do-Kun; Jung, Joo-Young; Suk Suh, Tae; Jo Hong, Key; Sil Lee, Keum

    2015-01-15

    Purpose: The purpose of this research is to perform the fast reconstruction of a prompt gamma ray image using a graphics processing unit (GPU) computation from boron neutron capture therapy (BNCT) simulations. Methods: To evaluate the accuracy of the reconstructed image, a phantom including four boron uptake regions (BURs) was used in the simulation. After the Monte Carlo simulation of the BNCT, the modified ordered subset expectation maximization reconstruction algorithm using the GPU computation was used to reconstruct the images with fewer projections. The computation times for image reconstruction were compared between the GPU and the central processing unit (CPU). Also, the accuracy of the reconstructed image was evaluated by a receiver operating characteristic (ROC) curve analysis. Results: The image reconstruction time using the GPU was 196 times faster than the conventional reconstruction time using the CPU. For the four BURs, the area under curve values from the ROC curve were 0.6726 (A-region), 0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). Conclusions: The tomographic image using the prompt gamma ray event from the BNCT simulation was acquired using the GPU computation in order to perform a fast reconstruction during treatment. The authors verified the feasibility of the prompt gamma ray image reconstruction using the GPU computation for BNCT simulations.

  13. Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer.

    PubMed

    Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito; Hiratsuka, Junichi; Yoshimura, Kenichi; Niimi, Miyuki; Kimura, Yoshihiro; Ariyoshi, Yasunori; Haginomori, Shin-Ichi; Sakurai, Yoshinori; Kinashi, Yuko; Masunaga, Shin-Ichiro; Fukushima, Masanori; Ono, Koji; Maruhashi, Akira

    2014-01-01

    We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10-12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7-40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted.

  14. Neutron Tube Design Study for Boron Neutron Capture TherapyApplication

    SciTech Connect

    Verbeke, J.M.; Lee, Y.; Leung, K.N.; Vujic, J.; Williams, M.D.; Wu, L.K.; Zahir, N.

    1998-01-04

    Radio-frequency (RF) driven ion sources are being developed in Lawrence Berkeley National Laboratory (LBNL) for sealed-accelerator-tube neutron generator application. By using a 5-cm-diameter RF-driven multicusp source H{sup +} yields over 95% have been achieved. These experimental findings will enable one to develop compact neutron generators based on the D-D or D-T fusion reactions. In this new neutron generator, the ion source, the accelerator and the target are all housed in a sealed metal container without external pumping. Recent moderator design simulation studies have shown that 14 MeV neutrons could be moderated to therapeutically useful energy ranges for boron neutron capture therapy (BNCT). The dose near the center of the brain with optimized moderators is about 65% higher than the dose obtained from a typical neutron spectrum produced by the Brookhaven Medical Research Reactor (BMRR), and is comparable to the dose obtained by other accelerator-based neutron sources. With a 120 keV and 1 A deuteron beam, a treatment time of {approx}35 minutes is estimated for BNCT.

  15. Boron neutron capture therapy of a murine mammary carcinoma using a lipophilic carboranyltetraphenylporphyrin.

    PubMed

    Miura, M; Morris, G M; Micca, P L; Lombardo, D T; Youngs, K M; Kalef-Ezra, J A; Hoch, D A; Slatkin, D N; Ma, R; Coderre, J A

    2001-04-01

    The first control of a malignant tumor in vivo by porphyrin- mediated boron neutron capture therapy (BNCT) is described. In mice bearing implanted EMT-6 mammary carcinomas, boron uptake using a single injection of either p-boronophenylalanine (BPA) or mercaptoundecahydrododecaborane (BSH) was compared with either a single injection or multiple injections of the carboranylporphyrin CuTCPH. The BSH and BPA doses used were comparable to the highest doses of these compounds previously administered in a single injection to rodents. For BNCT, boron concentrations averaged 85 microg (10)B/g in the tumor and 4 microg (10)B/g in blood 2 days after the last of six injections (over 32 h) that delivered a total of 190 microg CuTCPH/g body weight. During a single 15, 20, 25 or 30 MW-min exposure to the thermalized neutron beam of the Brookhaven Medical Research Reactor, a tumor received average absorbed doses of approximately 39, 52, 66 or 79 Gy, respectively. A long-term (>200 days) tumor control rate of 71% was achieved at a dose of 66 Gy with minimal damage to the leg. Equivalent long-term tumor control by a single exposure to 42 Gy X rays was achieved, but with greater damage to the irradiated leg.

  16. Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.

    PubMed

    Yanagië, H; Tomita, T; Kobayashi, H; Fujii, Y; Nonaka, Y; Saegusa, Y; Hasumi, K; Eriguchi, M; Kobayashi, T; Ono, K

    1997-01-01

    Immunoliposomes were prepared by conjugating anti-carcinoembryonic antigen (CEA) monoclonal antibody with liposomes containing [10B]compound. These immunoliposomes were shown to bind selectively to human pancreatic carcinoma cells (AsPC-1) bearing CEA on their surface. The cytotoxic effects of locally injected [10B]compound, multilamellar liposomes containing [10B]compound or [10B]immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with [10B]solution, 10B-containing liposomes or [10B]immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Injection of [10B]immunoliposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. Histopathologically, hyalinization and necrosis were found in 10B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. Boron neutron capture therapy (BNCT) with intratumoral injection of immunoliposomes is able to destroy malignant cells in the marginal portion between normal tissues and cancer tissues from the side of 4He generation.

  17. Sublethal and potentially lethal damage repair on thermal neutron capture therapy

    SciTech Connect

    Utsumi, H.; Ichihashi, M.; Kobayashi, T.; Elkind, M.M. )

    1989-07-01

    Tonicity shock or caffeine postirradiation treatment makes evident fast-type potentially lethal damage (PLD). Caffeine expresses fast-type PLD more efficiently than tonicity shock in X-irradiated B-16 mouse melanoma cells, compared with V79 Chinese hamster cells. The survival curves of thermal neutrons for either V79 or B-16 cells exhibit no shoulder. Neither V79 nor B-16 cells show the sublethal damage (SLD) repair of thermal neutrons. Caffeine-sensitive fast-type PLD repairs exist in X-irradiated B-16 cells, as well as V79 cells. The fast-type PLD repair of B-16 cells exposed to thermal neutrons alone is rather less than that of X-irradiated cells. Furthermore, an extremely low level of fast-type PLD repair of B-16 cells with 10B1-paraboronophenylalanine (BPA) preincubation (20 hours) followed by thermal neutron irradiation indicated that 10B(n,alpha)7Li reaction effectively eradicates actively growing melanoma cells. The plateau-phase B-16 cells are well able to repair the slow-type PLD of X-rays. However, cells can not repair the slow-type PLD induced by thermal neutron irradiation with or without 10B1-BPA preincubation. These results suggest that thermal neutron capture therapy can effectively kill radioresistant melanoma cells in both proliferating and quiescent phases.

  18. Inborn errors in metabolism and 4-boronophenylalanine-fructose-based boron neutron capture therapy.

    PubMed

    Laakso, Juha; Ruokonen, Inkeri; Lapatto, Risto; Kallio, Merja

    2003-11-01

    Infusions of boronophenylalanine-fructose complex (BPA-F), at doses up to 900 mg/kg of BPA and 860 mg/kg of fructose, have been used to deliver boron to cancer tissue for boron neutron capture therapy (BNCT). In patients with phenylketonuria (PKU), phenylalanine accumulates, which is harmful in the long run. PKU has been an exclusion criterion for BPA-F-mediated BNCT. Fructose is harmful to individuals with hereditary fructose intolerance (HFI) in amounts currently used in BNCT. The harmful effects are mediated through induction of hypoglycemia and acidosis, which may lead to irreversible organ damage or even death. Consequently, HFI should be added as an exclusion criterion for BNCT if fructose-containing solutions are used in boron carriers. Non-HFI subjects may also develop symptoms, such as gastrointestinal pain, if the fructose infusion rate is high. We therefore recommend monitoring of glucose levels and correcting possible hypoglycemia promptly. Except for some populations with extremely low PKU prevalence, HFI and PKU prevalences are similar, approximately 1 or 2 per 20,000.

  19. Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy

    PubMed Central

    Singh, Bikramjeet; Kaur, Gurpreet; Singh, Paviter; Singh, Kulwinder; Kumar, Baban; Vij, Ankush; Kumar, Manjeet; Bala, Rajni; Meena, Ramovatar; Singh, Ajay; Thakur, Anup; Kumar, Akshay

    2016-01-01

    Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT. PMID:27759052

  20. Verification of the computational dosimetry system in JAERI (JCDS) for boron neutron capture therapy.

    PubMed

    Kumada, H; Yamamoto, K; Matsumura, A; Yamamoto, T; Nakagawa, Y; Nakai, K; Kageji, T

    2004-08-07

    Clinical trials for boron neutron capture therapy (BNCT) by using the medical irradiation facility installed in Japan Research Reactor No. 4 (JRR-4) at Japan Atomic Energy Research Institute (JAERI) have been performed since 1999. To carry out the BNCT procedure based on proper treatment planning and its precise implementation, the JAERI computational dosimetry system (JCDS) which is applicable to dose planning has been developed in JAERI. The aim of this study was to verify the performance of JCDS. The experimental data with a cylindrical water phantom were compared with the calculation results using JCDS. Data of measurements obtained from IOBNCT cases at JRR-4 were also compared with retrospective evaluation data with JCDS. In comparison with phantom experiments, the calculations and the measurements for thermal neutron flux and gamma-ray dose were in a good agreement, except at the surface of the phantom. Against the measurements of clinical cases, the discrepancy of JCDS's calculations was approximately 10%. These basic and clinical verifications demonstrated that JCDS has enough performance for the BNCT dosimetry. Further investigations are recommended for precise dose distribution and faster calculation environment.

  1. A fundamental study on hyper-thermal neutrons for neutron capture therapy.

    PubMed

    Sakurai, Y; Kobayashi, T; Kanda, K

    1994-12-01

    The utilization of hyper-thermal neutrons, which have an energy spectrum with a Maxwellian distribution at a higher temperature than room temperature (300 K), was studied in order to improve the thermal neutron flux distribution at depth in a living body for neutron capture therapy. Simulation calculations were carried out using a Monte Carlo code 'MCNP-V3' in order to investigate the characteristics of hyper-thermal neutrons, i.e. (i) depth dependence of the neutron energy spectrum, and (ii) depth distribution of the reaction rate in a water phantom for materials with 1/v neutron absorption. It is confirmed that hyper-thermal neutron irradiation can improve the thermal neutron flux distribution in the deeper areas in a living body compared with thermal neutron irradiation. When hyper-thermal neutrons with a 3000 K Maxwellian distribution are incident on a body, the reaction rates of 1/v materials such as 14N, 10B etc are about twice that observed for incident thermal neutrons at 300 K, at a depth of 5 cm. The limit of the treatable depth for tumours having 30 ppm 10B is expected to be about 1.5 cm greater by utilizing hyper-thermal neutrons at 3000 K compared with the incidence of thermal neutrons at 300 K.

  2. Calculation of dose components in head phantom for boron neutron capture therapy.

    PubMed

    da Silva, Ademir X; Crispim, Verginia R

    2002-11-01

    Application of neutrons to cancer treatment has been a subject of considerable clinical and research interest since the discovery of the neutron by Chadwick in 1932 (3). Boron neutron capture therapy (BNCT) is a technique of radiation oncology which is used in treating brain cancer (glioblastoma multiform) or melanoma and that consists of preferentially loading a compound containing 10B into the tumor location, followed by the irradiation of the patient with a beam of neutron. Dose distribution for BNCT is mainly based on Monte Carlo simulations. In this work, the absorbed dose spatial distribution resultant from an idealized neutron beam incident upon ahead phantom is investigated using the Monte Carlo N-particles code, MCNP 4B. The phantom model used is based on the geometry of a circular cylinder on which sits an elliptical cylinder capped by half an ellipsoid representing the neck and head, both filled with tissue-equivalent material. The neutron flux and the contribution of individual absorbed dose components, as a function of depths and of radial distance from the beam axis (dose profiles) in phantom model, is presented and discussed. For the studied beam the maximum thermal neutron flux is at a depth of 2 cm and the maximum gamma dose at a depth of 4 cm.

  3. Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model

    SciTech Connect

    David W. Nigg

    2012-08-01

    Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA–BNCT, boronophenylalanine (BPA) ? neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA–BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks posttreatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA–BNCT, 2.7 ± 1.8 for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mgfell significantly to 19 ± 16 mg for BPA–BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA–BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA– BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.

  4. Lithium Nitride Synthesized by in situ Lithium Deposition and Ion Implantation for Boron Neutron Capture Therapy

    NASA Astrophysics Data System (ADS)

    Ishitama, Shintaro; Baba, Yuji; Fujii, Ryo; Nakamura, Masaru; Imahori, Yoshio

    Li3N synthesis on Li deposition layer was conducted without H2O and O2 by in situ lithium deposition in high vacuum chamber of 10-6 Pa and ion implantation techniques and the thermo-chemical stability of the Li3N/Li/Cu tri-layered target for Boron Neutron Capture Therapy (BNCT) under laser heating and air exposure was characterized by X-ray photoelectron spectroscopy (XPS). Following conclusions were derived; (1) Li3N/Li/Cu tri-layered target with very low oxide and carbon contamination was synthesized by in situ lithium vacuum deposition and N2+ ion implantation without H2O and O2 additions, (2) The starting temperature of evaporation of Li3N/Li/Cu tri-layered target increased by 120K compared to that of the Li/Cu target and (3) Remarkable oxidation and carbon contamination were observed on the surface of Li3N/Li/Cu after air exposure and these contaminated compositions was not removed by Ar+ heavy sputtering.

  5. Brain tumour and infiltrations dosimetry of boron neutron capture therapy combined with 252Cf brachytherapy.

    PubMed

    Brandão, Sâmia F; Campos, Tarcísio P R

    2012-04-01

    This article presents a dosimetric investigation of boron neutron capture therapy (BNCT) combined with (252)Cf brachytherapy for brain tumour control. The study was conducted through computational simulation in MCNP5 code, using a precise and discrete voxel model of a human head, in which a hypothetical brain tumour was incorporated. A boron concentration ratio of 1:5 for healthy-tissue: tumour was considered. Absorbed and biologically weighted dose rates and neutron fluency in the voxel model were evaluated. The absorbed dose rate results were exported to SISCODES software, which generates the isodose surfaces on the brain. Analyses were performed to clarify the relevance of boron concentrations in occult infiltrations far from the target tumour, with boron concentration ratios of 1:1 up to 1:50 for healthy-tissue:infiltrations and healthy-tissue:tumour. The average biologically weighted dose rates at tumour area exceed up to 40 times the surrounding healthy tissue dose rates. In addition, the biologically weighted dose rates from boron have the main contribution at the infiltrations, especially far from primary tumour. In conclusion, BNCT combined with (252)Cf brachytherapy is an alternative technique for brain tumour treatment because it intensifies dose deposition at the tumour and at infiltrations, sparing healthy brain tissue.

  6. Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy.

    PubMed

    Singh, Bikramjeet; Kaur, Gurpreet; Singh, Paviter; Singh, Kulwinder; Kumar, Baban; Vij, Ankush; Kumar, Manjeet; Bala, Rajni; Meena, Ramovatar; Singh, Ajay; Thakur, Anup; Kumar, Akshay

    2016-10-19

    Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT.

  7. Accelerator-based neutron source for boron neutron capture therapy (BNCT) and method

    DOEpatents

    Yoon, Woo Y.; Jones, James L.; Nigg, David W.; Harker, Yale D.

    1999-01-01

    A source for boron neutron capture therapy (BNCT) comprises a body of photoneutron emitter that includes heavy water and is closely surrounded in heat-imparting relationship by target material; one or more electron linear accelerators for supplying electron radiation having energy of substantially 2 to 10 MeV and for impinging such radiation on the target material, whereby photoneutrons are produced and heat is absorbed from the target material by the body of photoneutron emitter. The heavy water is circulated through a cooling arrangement to remove heat. A tank, desirably cylindrical or spherical, contains the heavy water, and a desired number of the electron accelerators circumferentially surround the tank and the target material as preferably made up of thin plates of metallic tungsten. Neutrons generated within the tank are passed through a surrounding region containing neutron filtering and moderating materials and through neutron delimiting structure to produce a beam or beams of epithermal neutrons normally having a minimum flux intensity level of 1.0.times.10.sup.9 neutrons per square centimeter per second. Such beam or beams of epithermal neutrons are passed through gamma ray attenuating material to provide the required epithermal neutrons for BNCT use.

  8. Accelerator-based neutron source for boron neutron capture therapy (BNCT) and method

    DOEpatents

    Yoon, W.Y.; Jones, J.L.; Nigg, D.W.; Harker, Y.D.

    1999-05-11

    A source for boron neutron capture therapy (BNCT) comprises a body of photoneutron emitter that includes heavy water and is closely surrounded in heat-imparting relationship by target material; one or more electron linear accelerators for supplying electron radiation having energy of substantially 2 to 10 MeV and for impinging such radiation on the target material, whereby photoneutrons are produced and heat is absorbed from the target material by the body of photoneutron emitter. The heavy water is circulated through a cooling arrangement to remove heat. A tank, desirably cylindrical or spherical, contains the heavy water, and a desired number of the electron accelerators circumferentially surround the tank and the target material as preferably made up of thin plates of metallic tungsten. Neutrons generated within the tank are passed through a surrounding region containing neutron filtering and moderating materials and through neutron delimiting structure to produce a beam or beams of epithermal neutrons normally having a minimum flux intensity level of 1.0{times}10{sup 9} neutrons per square centimeter per second. Such beam or beams of epithermal neutrons are passed through gamma ray attenuating material to provide the required epithermal neutrons for BNCT use. 3 figs.

  9. Gyrotron-driven high current ECR ion source for boron-neutron capture therapy neutron generator

    NASA Astrophysics Data System (ADS)

    Skalyga, V.; Izotov, I.; Golubev, S.; Razin, S.; Sidorov, A.; Maslennikova, A.; Volovecky, A.; Kalvas, T.; Koivisto, H.; Tarvainen, O.

    2014-12-01

    Boron-neutron capture therapy (BNCT) is a perspective treatment method for radiation resistant tumors. Unfortunately its development is strongly held back by a several physical and medical problems. Neutron sources for BNCT currently are limited to nuclear reactors and accelerators. For wide spread of BNCT investigations more compact and cheap neutron source would be much more preferable. In present paper an approach for compact D-D neutron generator creation based on a high current ECR ion source is suggested. Results on dense proton beams production are presented. A possibility of ion beams formation with current density up to 600 mA/cm2 is demonstrated. Estimations based on obtained experimental results show that neutron target bombarded by such deuteron beams would theoretically yield a neutron flux density up to 6·1010 cm-2/s. Thus, neutron generator based on a high-current deuteron ECR source with a powerful plasma heating by gyrotron radiation could fulfill the BNCT requirements significantly lower price, smaller size and ease of operation in comparison with existing reactors and accelerators.

  10. Toward prompt gamma spectrometry for monitoring boron distributions during extra corporal treatment of liver metastases by boron neutron capture therapy: a Monte Carlo simulation study.

    PubMed

    Khelifi, R; Nievaart, V A; Bode, P; Moss, R L; Krijger, G C

    2009-07-01

    A Monte Carlo calculation was carried out for boron neutron capture therapy (BNCT) of extra corporal liver phantom. The present paper describes the basis for a subsequent clinical application of the prompt gamma spectroscopy set-up aimed at in vivo monitoring of boron distribution. MCNP code was used first to validate the homogeneity in thermal neutron field in the liver phantom and simulate the gamma ray detection system (collimator and detector) in the treatment room. The gamma ray of 478 keV emitted by boron in small specific region can be detected and a mathematical formalism was used for the tomography image reconstruction.

  11. Chiral effective field theory predictions for muon capture on deuteron and {3}He.

    PubMed

    Marcucci, L E; Kievsky, A; Rosati, S; Schiavilla, R; Viviani, M

    2012-02-03

    The muon-capture reactions {2}H(μ{-},ν{μ})nn and {3}He(μ{-},ν{μ}){3}H are studied with nuclear potentials and charge-changing weak currents, derived in chiral effective field theory. The low-energy constants (LECs) c{D} and c{E}, present in the three-nucleon potential and (c{D}) axial-vector current, are constrained to reproduce the A=3 binding energies and the triton Gamow-Teller matrix element. The muon-capture rates on deuteron and {3}He are predicted to be 399±3  sec{-1} and 1494±21  sec{-1}, respectively. The spread accounts for the cutoff sensitivity, as well as uncertainties in the LECs and electroweak radiative corrections. By comparing the calculated and precisely measured rates on {3}He, a value for the induced pseudoscalar form factor is obtained in good agreement with the chiral perturbation theory prediction.

  12. Experimental verification of improved depth-dose distribution using hyper-thermal neutron incidence in neutron capture therapy.

    PubMed

    Sakurai, Y; Kobayashi, T

    2001-01-01

    We have proposed the utilization of 'hyper-thermal neutrons' for neutron capture therapy (NCT) from the viewpoint of the improvement in the dose distribution in a human body. In order to verify the improved depth-dose distribution due to hyper-thermal neutron incidence, two experiments were carried out using a test-type hyper-thermal neutron generator at a thermal neutron irradiation field in Kyoto University Reactor (KUR), which is actually utilized for NCT clinical irradiation. From the free-in-air experiment for the spectrum-shift characteristics, it was confirmed that the hyper-thermal neutrons of approximately 860 K at maximum could be obtained by the generator. From the phantom experiment, the improvement effect and the controllability for the depth-dose distribution were confirmed. For example, it was found that the relative neutron depth-dose distribution was about 1 cm improved with the 860 K hyper-thermal neutron incidence, compared to the normal thermal neutron incidence.

  13. Accelerator-Based Boron Neutron Capture Therapy and the Development of a Dedicated Tandem-Electrostatic-Quadrupole

    SciTech Connect

    Kreiner, A. J.; Di Paolo, H.; Burlon, A. A.; Valda, A. A.; Debray, M. E.; Somacal, H. R.; Minsky, D. M.; Kesque, J. M.; Giboudot, Y.; Levinas, P.; Fraiman, M.; Romeo, V.

    2007-10-26

    There is a generalized perception that the availability of suitable particle accelerators installed in hospitals, as neutron sources, may be crucial for the advancement of Boron Neutron Capture Therapy (BNCT). Progress on an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator for Accelerator-Based (AB)-BNCT is described here. The project goal is a machine capable of delivering 30 mA of 2.5 MeV protons to be used in conjunction with a neutron production target based on the {sup 7}Li(p,n){sup 7}Be reaction slightly beyond its resonance at 2.25 MeV. A folded tandem, with 1.25 MV terminal voltage, combined with an ESQ chain is being designed and constructed. A 30 mA proton beam of 2.5 MeV are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the {sup 7}Li(p,n){sup 7}Be reaction, to perform BNCT treatment for deep-seated tumors in less than an hour. The first design and construction of an ESQ module is discussed and its electrostatic fields are investigated theoretically and experimentally. Also new beam transport calculations through the accelerator are presented.

  14. Modification of the University of Washington Neutron Radiotherapy Facility for optimization of neutron capture enhanced fast-neutron therapy.

    PubMed

    Nigg, D W; Wemple, C A; Risler, R; Hartwell, J K; Harker, Y D; Laramore, G E

    2000-02-01

    A modified neutron production target assembly has been developed to provide improved performance of the proton-cyclotron-based neutron radiotherapy facility at the University of Washington for applications involving neutron capture enhanced fast-neutron therapy. The new target produces a neutron beam that yields essentially the same fast-neutron physical depth-dose distribution as is produced by the current UW clinical system, but that also has an increased fraction of BNCT enhancement relative to the total therapeutic dose. The modified target is composed of a 5-millimeter layer of beryllium, followed by a 2.5-millimeter layer of tungsten, with a water-cooled copper backing. Measurements of the free-field neutron spectrum of the beam produced by the new target were performed using activation foils with a direct spectral unfolding technique. Water phantom measurements were performed using a tissue-equivalent ion chamber to characterize the fast-neutron depth-dose curve and sodium activation in soda-lime glass beads to characterize the thermal-neutron flux (and thus the expected neutron capture dose enhancement) as a function of depth. The results of the various measurements were quite consistent with expectations based on the design calculations for the modified target. The spectrum of the neutron beam produced by the new target features an enhanced low-energy flux component relative to the spectrum of the beam produced by the standard UW target. However, it has essentially the same high-energy neutron flux, with a reduced flux component in the mid-range of the energy spectrum. As a result, the measured physical depth-dose curve in a large water phantom has the same shape compared to the case of the standard UW clinical beam, but approximately twice the level of BNCT enhancement per unit background neutron dose at depths of clinical interest. In-vivo clinical testing of BNCT-enhanced fast-neutron therapy for canine lung tumors using the new beam was recently

  15. Effect of Boron Neutron Capture Therapy (BNCT) on Normal Liver Regeneration: Towards a Novel Therapy for Liver Metastases

    SciTech Connect

    Jorge E. Cardoso; Elisa M. Heber; David W. Nigg; Osvaldo Calzetta; Herman Blaumann; Juan Longhino; Maria E. Itoiz; Eduardo Bumaschny; Emiliano Pozzi; Amanda E.Schwint; Verónica A. Trivillin

    2007-10-01

    The “TAORMINA project” developed a new method for Boron Neutron Capture Therapy (BNCT) of human multifocal unresectable liver metastases based on whole liver ex-situ BNCT mediated by boronophenylalanine (BPA), followed by whole liver autograft. This technique involved a high risk, prolonged anhepatic phase. The Roffo Institute liver surgeons (JEC) herein propose a novel technique to pursue ex-situ liver BNCT studies with a drastically lower surgical risk for the patient. The technique would involve, sequentially, ex-situ BNCT of left liver segments II and III, partial liver autograft, and induction of partial atrophy of the untreated right liver. The working hypothesis is that the atrophy of the right, untreated, diseased liver would stimulate regeneration of the left, treated, “cured” liver to yield a healthy liver mass, allowing for the resection of the remaining portion of diseased liver. This technique does not involve an anhepatic phase and would thus pose a drastically lower surgical risk to the patient but requires sine qua non that BNCT should not impair the regenerative capacity of normal hepatocytes. The aim of the present study was to assess the effect of therapeutic doses of BNCT mediated by BPA, GB-10 (Na2 10B10H10) or (GB- 10 + BPA) on normal liver regeneration in the Wistar rat employing partial hepatectomy as a regenerative stimulus. BNCT did not cause alterations in the outcome of normal liver regeneration, regenerated liver function or histology. We provide proof of principle to support the development of a novel, promising BNCT technique for the treatment of liver metastases.

  16. Coming of Age: The Evolving Field of Adventure Therapy

    ERIC Educational Resources Information Center

    Bandoroff, Scott, Ed.; Newes, Sandra, Ed.

    2006-01-01

    "Coming of Age" brings together a group of articles arising from the third International Adventure Therapy Conference held in Victoria, British Columbia, in April 2003. Together, they offer an overview of the field of Adventure Therapy in the new millennium, boasting a strong collection from the field's leading international figures:…

  17. Boron neutron capture therapy of brain tumors: an emerging therapeutic modality.

    PubMed

    Barth, R F; Soloway, A H; Goodman, J H; Gahbauer, R A; Gupta, N; Blue, T E; Yang, W; Tjarks, W

    1999-03-01

    Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10, a stable isotope, is irradiated with low-energy thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. For BNCT to be successful, a large number of 10B atoms must be localized on or preferably within neoplastic cells, and a sufficient number of thermal neutrons must be absorbed by the 10B atoms to sustain a lethal 10B (n, alpha) lithium-7 reaction. There is a growing interest in using BNCT in combination with surgery to treat patients with high-grade gliomas and possibly metastatic brain tumors. The present review covers the biological and radiobiological considerations on which BNCT is based, boron-containing low- and high-molecular weight delivery agents, neutron sources, clinical studies, and future areas of research. Two boron compounds currently are being used clinically, sodium borocaptate and boronophenylalanine, and a number of new delivery agents are under investigation, including boronated porphyrins, nucleosides, amino acids, polyamines, monoclonal and bispecific antibodies, liposomes, and epidermal growth factor. These are discussed, as is optimization of their delivery. Nuclear reactors currently are the only source of neutrons for BNCT, and the fission reaction within the core produces a mixture of lower energy thermal and epithermal neutrons, fast or high-energy neutrons, and gamma-rays. Although thermal neutron beams have been used clinically in Japan to treat patients with brain tumors and cutaneous melanomas, epithermal neutron beams now are being used in the United States and Europe because of their superior tissue-penetrating properties. Currently, there are clinical trials in progress in the United States, Europe, and Japan using a combination of debulking surgery and then BNCT to treat patients with glioblastomas. The American and European studies are Phase I trials using boronophenylalanine and sodium borocaptate, respectively

  18. A nude rat model for neutron capture therapy of human intracerebral melanoma

    SciTech Connect

    Barth, R.F.; Matalka, K.Z.; Bailey, M.Q.; Staubus, A.E.; Soloway, A.H.; Moeschberger, M.L. ); Coderre, J.A. ); Rofstad, E.K. )

    1994-03-30

    The present study was carried out to determine the efficacy of Boron Neutron Capture Therapy (BNCT) for intracerebral melanoma using nude rats, the human melanoma cell line MRA 27, and boronophenylalanine as the capture agent. MRA 27 cells (2 [times] 10[sup 5]) were implanted intracerebrally, and 30 days later, 120 mg of [sup 10]B-L-BPA were injected intraperitoneally into nude rats. Thirty days following implantation, tumor bearing rats were irradiated at the Brookhaven Medical Research Reactor. Six hours following administration of BPA, tumor, blood, and normal brain boron-10 levels were 23.7, 9.4, and 8.4 [mu]g/g respectively. Median survival time of untreated rats was 44 days compared to 76 days and 93 days for those receiving physical doses of 2.73 Gy and 3.64 Gy, respectively. Rats that have received both [sup 10]B-BPA and physical doses of 1.82, 2.73, or 3.64 Gy had median survival times of 170, 182, and 262 days, respectively. Forty percent of rats that had received the highest tumor dose (10.1 Gy) survived for > 300 days and in a replicate experiment 21% of the rats were longterm survivors (>220 days). Animals that received 12 Gy in a single dose or 18 Gy fractionated (2 Gy [times] 9) of gamma photons from a [sup 137]Cs source had median survival times of 86 and 79 days, respectively, compared to 47 days for untreated animals. Histopathologic examination of the brains of longterm surviving rats, euthanized at 8 or 16 months following BNCT, showed no residual tumor, but dense accumulations of melanin laden macrophages and minimal gliosis were observed. Significant prolongations in median survival time were noted in nude rats with intracerebral human melanoma that had received BNCT, thereby suggesting therapeutic efficacy. Large animal studies should be carried out to further assess BNCT of intracerebral melanoma before any human trials are contemplated. 49 refs., 7 figs., 2 tabs.

  19. Dose homogeneity in boron neutron capture therapy using an epithermal neutron beam.

    PubMed

    Konijnenberg, M W; Dewit, L G; Mijnheer, B J; Raaijmakers, C P; Watkins, P R

    1995-06-01

    Simulation models based on the neutron and photon Monte Carlo code MCNP were used to study the therapeutic possibilities of the HB11 epithermal neutron beam at the High Flux Reactor in Petten. Irradiations were simulated in two types of phantoms filled with water or tissue-equivalent material for benchmark treatment planning calculations. In a cuboid phantom the influence of different field sizes on the thermal-neutron-induced dose distribution was investigated. Various shapes of collimators were studied to test their efficacy in optimizing the thermal-neutron distribution over a planning target volume and healthy tissues. Using circular collimators of 8, 12 and 15 cm diameter it was shown that with the 15-cm field a relatively larger volume within 85% of the maximum neutron-induced dose was obtained than with the 8- or 12-cm-diameter field. However, even for this large field the maximum diameter of this volume was 7.5 cm. In an ellipsoid head phantom the neutron-induced dose was calculated assuming the skull to contain 10 ppm 10B, the brain 5 ppm 10B and the tumor 30 ppm 10B. It was found that with a single 15-cm-diameter circular beam a very inhomogenous dose distribution in a typical target volume was obtained. Applying two equally weighted opposing 15-cm-diameter fields, however, a dose homogeneity within +/- 10% in this planning target volume was obtained. The dose in the surrounding healthy brain tissue is 30% at maximum of the dose in the center of the target volume. Contrary to the situation for the 8-cm field, combining four fields of 15 cm diameter gave no large improvement of the dose homogeneity over the target volume or a lower maximum dose in the healthy brain. Dose-volume histograms were evaluated for the planning target volume as well as for the healthy brain to compare different irradiation techniques, yielding a graphical confirmation of the above conclusions. Therapy with BNCT on brain tumors must be performed either with an 8-cm four-field

  20. Double electron capture between an α particle and a helium atom in the presence of an intense laser field

    NASA Astrophysics Data System (ADS)

    Li, Shu-Min; Miao, Yan-Gang; Zhou, Zi-Fang; Chen, Ji; Liu, Yao-Yang

    1998-05-01

    In the first Born approximation, the symmetrical double-electron-capture collision between an α particle and a helium atom in the presence of an intense laser field is studied. The capture cross section is promoted considerably and is an increasing function of the ratio of the laser amplitude to frequency. With increasing impact energy, the dressing modification becomes notable.

  1. Immunomagnetically Captured Thermophilic Sulfate-Reducing Bacteria from North Sea Oil Field Waters

    PubMed Central

    Christensen, Bjørn; Torsvik, Terje; Lien, Torleiv

    1992-01-01

    Immunomagnetic beads (IMB) were used to recover thermophilic sulfate-reducing bacteria from oil field waters from oil production platforms in the Norwegian sector of the North Sea. IMB coated with polyclonal antibodies against whole-cell antigens of the thermophilic Thermodesulfobacterium mobile captured strains GFA1, GFA2, and GFA3. GFA1 was serologically and morphologically identical to T. mobile. GFA2 and GFA3 were spore forming and similar to the Desulfotomaculum strains T90A and T93B previously isolated from North Sea oil field waters by a classical enrichment procedure. Western blots (immunoblots) of whole cells showed that GFA2, GFA3, T90A, and T93B are different serotypes of the same Desulfotomaculum species. Monoclonal antibodies (MAb) against T. mobile type strain cells were produced and used as capture agents on IMB. These MAb, named A4F4, were immunoglobulin M; they were specific to T. mobile and directed against lipopolysaccharides. The prevailing cells immunocaptured with MAb A4F4 were morphologically and serologically similar to T. mobile type strain cells. T. mobile was not detected in these oil field waters by classical enrichment procedures. Furthermore, extraction with antibody-coated IMB allowed pure strains to be isolated directly from primary enrichment cultures without prior time-consuming subculturing and consecutive transfers to selective media. Images PMID:16348693

  2. Optimization of Boron Neutron Capture Therapy for the Treatment of Undifferentiated Thyroid Cancer

    SciTech Connect

    Dagrosa, Maria Alejandra; Thomasz, Lisa M.Sc.; Longhino, Juan; Perona, Marina; Calzetta, Osvaldo; Blaumann, Herman; Rebagliati, Raul Jimenez; Cabrini, Romulo; Kahl, Steven; Juvenal, Guillermo Juan; Pisarev, Mario Alberto

    2007-11-15

    Purpose: To analyze the possible increase in efficacy of boron neutron capture therapy (BNCT) for undifferentiated thyroid carcinoma (UTC) by using p-boronophenylalanine (BPA) plus 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX (BOPP) and BPA plus nicotinamide (NA) as a radiosensitizer of the BNCT reaction. Methods and Materials: Nude mice were transplanted with a human UTC cell line (ARO), and after 15 days they were treated as follows: (1) control, (2) NCT (neutrons alone), (3) NCT plus NA (100 mg/kg body weight [bw]/day for 3 days), (4) BPA (350 mg/kg bw) + neutrons, (5) BPA + NA + neutrons, and (6) BPA + BOPP (60 mg/kg bw) + neutrons. The flux of the mixed (thermal + epithermal) neutron beam was 2.8 x 10{sup 8} n/cm{sup 2}/sec for 83.4 min. Results: Neutrons alone or with NA caused some tumor growth delay, whereas in the BPA, BPA + NA, and BPA + BOPP groups a 100% halt of tumor growth was observed in all mice at 26 days after irradiation. When the initial tumor volume was 50 mm{sup 3} or less, complete remission was found with BPA + NA (2 of 2 mice), BPA (1 of 4), and BPA + BOPP (7 of 7). After 90 days of complete regression, recurrence of the tumor was observed in BPA + NA (2 of 2) and BPA + BOPP (1 of 7). The determination of apoptosis in tumor samples by measurements of caspase-3 activity showed an increase in the BNCT (BPA + NA) group at 24 h (p < 0.05 vs. controls) and after the first week after irradiation in the three BNCT groups. Terminal transferase dUTP nick end labeling analysis confirmed these results. Conclusions: Although NA combined with BPA showed an increase of apoptosis at early times, only the group irradiated after the combined administration of BPA and BOPP showed a significantly improved therapeutic response.

  3. First application of dynamic infrared imaging in boron neutron capture therapy for cutaneous malignant melanoma

    SciTech Connect

    Santa Cruz, G. A.; Gonzalez, S. J.; Bertotti, J.; Marin, J.

    2009-10-15

    Purpose: The purpose of this study is to assess the potential of dynamic infrared imaging (DIRI) as a functional, noninvasive technique for evaluating the skin acute toxicity and tumor control within the framework of the Argentine boron neutron capture therapy (BNCT) program for cutaneous malignant melanoma. Methods: Two patients enrolled in the Argentine phase I/II BNCT clinical trial for cutaneous malignant melanoma were studied with DIRI. An uncooled infrared camera, providing a video output signal, was employed to register the temperature evolution of the normal skin and tumor regions in patients subjected to a mild local cooling (cold stimulus). In order to study the spatial correlation between dose and acute skin reactions, three-dimensional representations of the superficial dose delivered to skin were constructed and cameralike projections of the dose distribution were coregistered with visible and infrared images. Results: The main erythematous reaction was observed clinically between the second and fifth week post-BNCT. Concurrently, with its clinical onset, a reactive increase above the basal skin temperature was observed with DIRI in the third week post-BNCT within regions that received therapeutic doses. Melanoma nodules appeared as highly localized hyperthermic regions. 2 min after stimulus, these regions reached a temperature plateau and increased in size. Temperature differences with respect to normal skin up to 10 deg. C were observed in the larger nodules. Conclusions: Preliminary results suggest that DIRI, enhanced by the application of cold stimuli, may provide useful functional information associated with the metabolism and vasculature of tumors and inflammatory processes related to radiation-induced changes in the skin as well. These capabilities are aimed at complementing the clinical observations and standard imaging techniques, such as CT and Doppler ultrasound.

  4. Boron uptake measurements in a rat model for Boron Neutron Capture Therapy of lung tumours.

    PubMed

    Bortolussi, S; Bakeine, J G; Ballarini, F; Bruschi, P; Gadan, M A; Protti, N; Stella, S; Clerici, A; Ferrari, C; Cansolino, L; Zonta, C; Zonta, A; Nano, R; Altieri, S

    2011-02-01

    Lung carcinoma is the leading cause of cancer mortality in the Western countries. Despite the introduction over the last few years of new therapeutic agents, survival from lung cancer has shown no discernible improvement in the last 20 years. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely. The selective boron uptake in the tumour with respect to healthy tissues makes Boron Neutron Capture Therapy a potentially advantageous option in the treatment of tumours that affect whole vital organs, and that are surgically inoperable. To study the possibility of applying BNCT to the treatment of diffuse pulmonary tumours, an animal model for boron uptake measurements in lung metastases was developed. Both healthy and tumour-bearing rats were infused with Boronophenylalanine (BPA) and sacrificed at different time intervals after drug administration. The lungs were extracted, and prepared for boron analysis by neutron autoradiography and α-spectroscopy. The boron concentrations in tumour and normal lung were plotted as a function of the time elapsed after BPA administration. The concentration in tumour is almost constant within the error bars for all the time intervals of the experiment (1-8 h), while the curve in normal lung decreases after 4 h from BPA infusion. At 4 h, the ratio of boron concentration in tumour to boron concentration in healthy lung is higher than 3, and it stays above this level up to 8 h. Also the images of boron distribution in the samples, obtained by neutron autoradiography, show a selective absorption in the metastases.

  5. Exploring Boron Neutron Capture Therapy for non-small cell lung cancer.

    PubMed

    Farías, Rubén O; Bortolussi, Silva; Menéndez, Pablo R; González, Sara J

    2014-12-01

    Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high LET radiation. It consists in the enrichment of tumour with (10)B and in the successive irradiation of the target with low energy neutrons producing charged particles that mainly cause non-repairable damages to the cells. The feasibility to treat Non Small Cells Lung Cancer (NSCLC) with BNCT was explored. This paper proposes a new approach to determine treatment plans, introducing the possibility to choose the irradiation start and duration to maximize the tumour dose. A Tumour Control Probability (TCP) suited for lung BNCT as well as other high dose radiotherapy schemes was also introduced. Treatment plans were evaluated in localized and disseminated lung tumours. Semi-ideal and real energy spectra beams were employed to assess the best energy range and the performance of non-tailored neutron sources for lung tumour treatments. The optimal neutron energy is within [500 eV-3 keV], lower than the 10 keV suggested for the treatment of deep-seated tumours in the brain. TCPs higher than 0.6 and up to 0.95 are obtained for all cases. Conclusions drawn from [Suzuki et al., Int Canc Conf J 1 (4) (2012) 235-238] supporting the feasibility of BNCT for shallow lung tumours are confirmed, however discussions favouring the treatment of deeper lesions and disseminated disease are also opened. Since BNCT gives the possibility to deliver a safe and potentially effective treatment for NSCLC, it can be considered a suitable alternative for patients with few or no treatment options.

  6. Biodistribution of sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) in an oral cancer model.

    PubMed

    Garabalino, Marcela A; Heber, Elisa M; Monti Hughes, Andrea; González, Sara J; Molinari, Ana J; Pozzi, Emiliano C C; Nievas, Susana; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Bauer, William; Trivillin, Verónica A; Schwint, Amanda E

    2013-08-01

    Boron neutron capture therapy (BNCT) is based on selective accumulation of ¹⁰B carriers in tumor followed by neutron irradiation. We previously proved the therapeutic success of BNCT mediated by the boron compounds boronophenylalanine and sodium decahydrodecaborate (GB-10) in the hamster cheek pouch oral cancer model. Based on the clinical relevance of the boron carrier sodium borocaptate (BSH) and the knowledge that the most effective way to optimize BNCT is to improve tumor boron targeting, the specific aim of this study was to perform biodistribution studies of BSH in the hamster cheek pouch oral cancer model and evaluate the feasibility of BNCT mediated by BSH at nuclear reactor RA-3. The general aim of these studies is to contribute to the knowledge of BNCT radiobiology and optimize BNCT for head and neck cancer. Sodium borocaptate (50 mg ¹⁰B/kg) was administered to tumor-bearing hamsters. Groups of 3-5 animals were killed humanely at nine time-points, 3-12 h post-administration. Samples of blood, tumor, precancerous pouch tissue, normal pouch tissue and other clinically relevant normal tissues were processed for boron measurement by optic emission spectroscopy. Tumor boron concentration peaked to therapeutically useful boron concentration values of 24-35 ppm. The boron concentration ratio tumor/normal pouch tissue ranged from 1.1 to 1.8. Pharmacokinetic curves showed that the optimum interval between BSH administration and neutron irradiation was 7-11 h. It is concluded that BNCT mediated by BSH at nuclear reactor RA-3 would be feasible.

  7. Macroscopic geometric heterogeneity effects in radiation dose distribution analysis for boron neutron capture therapy.

    PubMed

    Moran, J M; Nigg, D W; Wheeler, F J; Bauer, W F

    1992-01-01

    Calculations of radiation flux and dose distributions for boron neutron capture therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This paper describes such a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for the tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for this model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous-tissue model. Comparison of the results showed that peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10%-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models.

  8. Boron neutron capture therapy (BNCT): implications of neutron beam and boron compound characteristics.

    PubMed

    Wheeler, F J; Nigg, D W; Capala, J; Watkins, P R; Vroegindeweij, C; Auterinen, I; Seppälä, T; Bleuel, D

    1999-07-01

    The potential efficacy of boron neutron capture therapy (BNCT) for malignant glioma is a significant function of epithermal-neutron beam biophysical characteristics as well as boron compound biodistribution characteristics. Monte Carlo analyses were performed to evaluate the relative significance of these factors on theoretical tumor control using a standard model. The existing, well-characterized epithermal-neutron sources at the Brookhaven Medical Research Reactor (BMRR), the Petten High Flux Reactor (HFR), and the Finnish Research Reactor (FiR-1) were compared. Results for a realistic accelerator design by the E. O. Lawrence Berkeley National Laboratory (LBL) are also compared. Also the characteristics of the compound p-Boronophenylaline Fructose (BPA-F) and a hypothetical next-generation compound were used in a comparison of the BMRR and a hypothetical improved reactor. All components of dose induced by an external epithermal-neutron beam fall off quite rapidly with depth in tissue. Delivery of dose to greater depths is limited by the healthy-tissue tolerance and a reduction in the hydrogen-recoil and incident gamma dose allow for longer irradiation and greater dose at a depth. Dose at depth can also be increased with a beam that has higher neutron energy (without too high a recoil dose) and a more forward peaked angular distribution. Of the existing facilities, the FiR-1 beam has the better quality (lower hydrogen-recoil and incident gamma dose) and a penetrating neutron spectrum and was found to deliver a higher value of Tumor Control Probability (TCP) than other existing beams at shallow depth. The greater forwardness and penetration of the HFR the FiR-1 at greater depths. The hypothetical reactor and accelerator beams outperform at both shallow and greater depths. In all cases, the hypothetical compound provides a significant improvement in efficacy but it is shown that the full benefit of improved compound is not realized until the neutron beam is fully

  9. A benchmark analysis of radiation flux distribution for Boron Neutron Capture Therapy of canine brain tumors

    SciTech Connect

    Moran, J.M.

    1992-02-01

    Calculations of radiation flux and dose distributions for Boron Neutron Capture Therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly-heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This work describes a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador Retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador Retriever head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for the model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous tissue model. Comparison of the results showed that the peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models.

  10. An international dosimetry exchange for boron neutron capture therapy. Part I: Absorbed dose measurements.

    PubMed

    Binns, P J; Riley, K J; Harling, O K; Kiger, W S; Munck af Rosenschöld, P M; Giusti, V; Capala, J; Sköld, K; Auterinen, I; Serén, T; Kotiluoto, P; Uusi-Simola, J; Marek, M; Viererbl, L; Spurny, F

    2005-12-01

    An international collaboration was organized to undertake a dosimetry exchange to enable the future combination of clinical data from different centers conducting neutron capture therapy trials. As a first step (Part I) the dosimetry group from the Americas, represented by MIT, visited the clinical centers at Studsvik (Sweden), VTT Espoo (Finland), and the Nuclear Research Institute (NRI) at Rez (Czech Republic). A combined VTT/NRI group reciprocated with a visit to MIT. Each participant performed a series of dosimetry measurements under equivalent irradiation conditions using methods appropriate to their clinical protocols. This entailed in-air measurements and dose versus depth measurements in a large water phantom. Thermal neutron flux as well as fast neutron and photon absorbed dose rates were measured. Satisfactory agreement in determining absorbed dose within the experimental uncertainties was obtained between the different groups although the measurement uncertainties are large, ranging between 3% and 30% depending upon the dose component and the depth of measurement. To improve the precision in the specification of absorbed dose amongst the participants, the individually measured dose components were normalized to the results from a single method. Assuming a boron concentration of 15 microg g(-1) that is typical of concentrations realized clinically with the boron delivery compound boronophenylalanine-fructose, systematic discrepancies in the specification of the total biologically weighted dose of up to 10% were apparent between the different groups. The results from these measurements will be used in future to normalize treatment plan calculations between the different clinical dosimetry protocols as Part II of this study.

  11. Probabilistic study of well capture zones distribution at the Lauswiesen field site.

    PubMed

    Riva, M; Guadagnini, L; Guadagnini, A; Ptak, T; Martac, E

    2006-11-20

    The delineation of well capture zones is of utmost environmental and engineering relevance as pumping wells are commonly used both for drinking water supply needs, where protection zones have to be defined, and for investigation and remediation of contaminated aquifers. We analyze the probabilistic nature of well capture zones within the well field located at the "Lauswiesen" experimental site. The test site is part of an alluvial heterogeneous aquifer located in the Neckar river valley, close to the city of Tübingen in South-West Germany. We explore the effect of different conceptual models of the structure of aquifer heterogeneities on the delineation of three-dimensional probabilistic well catchment and time-related capture zones, in the presence of migration of conservative solutes. The aquifer is modeled as a three-dimensional, doubly stochastic composite medium, where distributions of geo-materials and hydraulic properties are uncertain. We study the relative importance of uncertain facies geometry and uncertain hydraulic conductivity and porosity on predictions of catchment and solute time of travel to the pumping well by focusing on cases in which (1) the facies distribution is random, but the hydraulic properties of each material are fixed, and (2) both facies geometry and material properties vary stochastically. The problem is tackled within a conditional numerical Monte Carlo framework. Results are provided in terms of probabilistic demarcations of the three-dimensional well catchment and time-related capture zones. Our findings suggest that the uncertainty associated with the prediction of the location of the outer boundary of well catchment at the "Lauswiesen" site is significantly affected by the conceptual model adopted to incorporate the heterogeneous nature of the aquifer domain in a predictive framework. Taking into account randomness of both lithofacies distribution and materials hydraulic conductivity allows recognizing the existence of

  12. Experimental evaluation of boron neutron capture therapy of human breast carcinoma implanted on nude mice

    NASA Astrophysics Data System (ADS)

    Bose, Satya Ranjan

    2000-06-01

    An in-pool small animal irradiation neutron tube (SAINT) facility was designed, constructed and installed at the University of Virginia Nuclear Research Reactor (UVAR). Thermal neutron flux profiles were measured by foil activation analysis (gold) and verified with DORT and MCNP computer code models. The gamma-ray absorbed dose in the neutron-gamma mixed field was determined from TLD measurements. The SAINT thermal neutron flux was used to investigate the well characterized human breast cancer cell line MCF-7B on both in-vitro samples and in- vivo animal subjects. Boronophenylalanine (BPA enriched in 95% 10B) was used as a neutron capturing agent. The in-vitro response of MCF-7B human breast carcinoma cells to BPA in a mixed field of neutron-gamma radiation or pure 60Co gamma radiation was investigated. The best result (lowest surviving fraction) was observed in cell cultures pre-incubated with BPA and given the neutron irradiation. The least effective treatment consisted of 60Co irradiation only. Immunologically deficient nude mice were inoculated subcutaneously with human breast cancer MCF-7B cells and estradiol pellets (to support tumor growth). The tumor volume in the mouse control group increased over time, as expected. The group of mice exposed only to neutron treatment exhibited initial tumor volume reduction lasting until 35 days following the treatment, followed by renewed tumor growth. Both groups given BPA plus neutron treatment showed continuous reduction in tumor volume over the 55-day observation period. The group given the higher BPA concentration showed the best tumor reduction response. The results on both in-vitro and in-vivo studies showed increased cell killing with BPA, substantiating the incorporation of BPA into the tumor or cell line. Therefore, BNCT may be a possible choice for the treatment of human breast carcinoma. However, prior to the initiation of any clinical studies, it is necessary to determine the therapeutic efficacy in a large

  13. Synthesis of Sugar-Boronic Acid Derivatives: A Class of Potential Agents for Boron Neutron Capture Therapy.

    PubMed

    Imperio, Daniela; Del Grosso, Erika; Fallarini, Silvia; Lombardi, Grazia; Panza, Luigi

    2017-04-07

    To date, sugar analogues that contain boronic acids as substitutes for hydroxyl groups are a class of compounds nearly unknown in the literature. The challenging synthesis of two sugar-boronic acid analogues is described, and data are retrieved on their solution behavior, stability, and toxicity. As these compounds were expected to mimic the behavior of carbohydrates, they were tested in regards to their future development as potential boron neutron capture therapy agents.

  14. Clinical trials of boron neutron capture therapy [in humans] [at Beth Israel Deaconess Medical Center][at Brookhaven National Laboratory

    SciTech Connect

    Wallace, Christine

    2001-05-29

    Assessment of research records of Boron Neutron Capture Therapy was conducted at Brookhaven National Laboratory and Beth Israel Deaconess Medical Center using the Code of Federal Regulations, FDA Regulations and Good Clinical Practice Guidelines. Clinical data were collected from subjects' research charts, and differences in conduct of studies at both centers were examined. Records maintained at Brookhaven National Laboratory were not in compliance with regulatory standards. Beth Israel's records followed federal regulations. Deficiencies discovered at both sites are discussed in the reports.

  15. Biological efficacy of boronated low-density lipoprotein for boron neutron capture therapy as measured in cell culture.

    PubMed

    Laster, B H; Kahl, S B; Popenoe, E A; Pate, D W; Fairchild, R G

    1991-09-01

    Low-density lipoproteins (LDLs) are known to be internalized by the cell through receptor-mediated mechanisms. There is evidence that LDLs may be taken up avidly by tumor cells to provide cholesterol for the synthesis of cell membranes. Thus, the possibility exists that LDLs may provide an ideal vehicle for the transport of boron to tumor cells for boron neutron capture therapy. A boronated analogue of LDL has recently been synthesized for possible application in boron neutron capture therapy. The analogue was tested in cell culture for uptake and biological efficacy in the thermal neutron beam at the Brookhaven Medical Research Reactor. It was found that boron concentrations 10 times higher than that required in tumors for boron neutron capture therapy were easily obtained and that the amount of uptake was consistent with a receptor-mediated binding mechanism. The measured intracellular concentration of approximately 240 micrograms 10B/g cells is significantly higher than that obtained with any other boron compound previously evaluated for possible clinical application.

  16. Borocaptate sodium: a potential boron delivery compound for boron neutron capture therapy evaluated in dogs with spontaneous intracranial tumors.

    PubMed Central

    Kraft, S L; Gavin, P R; DeHaan, C E; Leathers, C W; Bauer, W F; Miller, D L; Dorn, R V

    1992-01-01

    Borocaptate sodium (Na2B12H11SH) is a boron-carrying compound under consideration for use in boron neutron capture therapy. The biodistribution of boron from borocaptate sodium administration will partly determine boron neutron capture therapy efficacy and normal tissue radiation tolerance. The biodistribution of boron was determined in 30 dogs with spontaneous intracranial tumors at 2, 6, or 12 hr after intravenous borocaptate sodium infusion. Blood and tissue boron concentrations were measured using inductively coupled plasma atomic emission spectroscopy. Mean tumor boron concentration (mean +/- standard error) was 35.9 +/- 4.6 (n = 15), 22.5 +/- 6.0 (n = 9), and 7.0 +/- 1.1 micrograms of boron per g (n = 6) at 2, 6, and 12 hr, respectively, after borocaptate sodium infusion. Peritumor boron concentrations were elevated above that of normal brain in half of the dogs. Normal brain boron concentration (mean +/- standard error) was 4.0 +/- 0.5, 2.0 +/- 0.4, and 2.0 +/- 0.3 micrograms of boron per g at 2, 6, and 12 hr after infusion, respectively. Some cranial and systemic tissues, and blood, had high boron concentration relative to tumor tissue. Geometric dose sparing should partly offset these relatively high normal tissue and blood concentrations. Borocaptate sodium biodistribution is favorable because tumor boron concentrations of recommended magnitude for boron neutron capture therapy were obtained and there was a high tumor-to-normal brain boron concentration ratio. PMID:1465427

  17. Effect of piezoelectric field of threading dislocations on electron transport and capture in nitride semiconductors

    NASA Astrophysics Data System (ADS)

    Romanov, Dmitri; Auner, Gregory

    2001-03-01

    In nitride semiconductor structures, stress is known to induce considerable electric fields due to piezoelectric effect. We consider an AlN layer grown on a sapphire substrate and containing a number of threading dislocations. Most them are edge dislocations running in the growth direction. The strain field of such a dislocation results in electric field aligned with the dislocation axis and having alternate directions in the areas of compression and tension. These electric fields make for anisotropic electron diffusion in the layer. They also change the rates of electron capture by impurities, depending on the distance to the dislocation core. We apply these results to photoexcited electrons in a GaN/AlN quantum dot system where the dot nucleation occurred preferably in the tension regions near the dislocations [1]. The biased diffusion leads to photoinduced polarization of the dot-containing layer even in the absence of external electric field. [1] J.L. Rouviere, J. Simon, N. Pelekanos, B. Daudin, and G. Feuillet, Appl. Phys. Lett., 75, 2632-2634 (1999)

  18. Monte Carlo based treatment planning systems for Boron Neutron Capture Therapy in Petten, The Netherlands

    NASA Astrophysics Data System (ADS)

    Nievaart, V. A.; Daquino, G. G.; Moss, R. L.

    2007-06-01

    Boron Neutron Capture Therapy (BNCT) is a bimodal form of radiotherapy for the treatment of tumour lesions. Since the cancer cells in the treatment volume are targeted with 10B, a higher dose is given to these cancer cells due to the 10B(n,α)7Li reaction, in comparison with the surrounding healthy cells. In Petten (The Netherlands), at the High Flux Reactor, a specially tailored neutron beam has been designed and installed. Over 30 patients have been treated with BNCT in 2 clinical protocols: a phase I study for the treatment of glioblastoma multiforme and a phase II study on the treatment of malignant melanoma. Furthermore, activities concerning the extra-corporal treatment of metastasis in the liver (from colorectal cancer) are in progress. The irradiation beam at the HFR contains both neutrons and gammas that, together with the complex geometries of both patient and beam set-up, demands for very detailed treatment planning calculations. A well designed Treatment Planning System (TPS) should obey the following general scheme: (1) a pre-processing phase (CT and/or MRI scans to create the geometric solid model, cross-section files for neutrons and/or gammas); (2) calculations (3D radiation transport, estimation of neutron and gamma fluences, macroscopic and microscopic dose); (3) post-processing phase (displaying of the results, iso-doses and -fluences). Treatment planning in BNCT is performed making use of Monte Carlo codes incorporated in a framework, which includes also the pre- and post-processing phases. In particular, the glioblastoma multiforme protocol used BNCT_rtpe, while the melanoma metastases protocol uses NCTPlan. In addition, an ad hoc Positron Emission Tomography (PET) based treatment planning system (BDTPS) has been implemented in order to integrate the real macroscopic boron distribution obtained from PET scanning. BDTPS is patented and uses MCNP as the calculation engine. The precision obtained by the Monte Carlo based TPSs exploited at Petten

  19. Technical aspects of boron neutron capture therapy at the BNL Medical Research Reactor

    SciTech Connect

    Holden, N.E.; Rorer, D.C.; Patti, F.J.; Liu, H.B.; Reciniello, R.; Chanana, A.D.

    1997-07-01

    The Brookhaven Medical Research Reactor, BMRR, is a 3 MW heterogeneous, tank-type, light water cooled and moderated, graphite reflected reactor, which was designed for biomedical studies. Early BNL work in Boron Neutron Capture Therapy (BNCT) used a beam of thermal neutrons for experimental treatment of brain tumors. Research elsewhere and at BNL indicated that higher energy neutrons would be required to treat deep seated brain tumors. Epithermal neutrons would be thermalized as they penetrated the brain and peak thermal neutron flux densities would occur at the depth of brain tumors. One of the two BMRR thermal port shutters was modified in 1988 to include plates of aluminum and aluminum oxide to provide an epithermal port. Lithium carbonate in polyethylene was added in 1991 around the bismuth port to reduce the neutron flux density coming from outside the port. To enhance the epithermal neutron flux density, the two vertical thimbles A-3 (core edge) and E-3 (in core) were replaced with fuel elements. There are now four fuel elements of 190 grams each and 28 fuel elements of 140 grams each for a total of 4.68 kg of {sup 235}U in the core. The authors have proposed replacing the epithermal shutter with a fission converter plate shutter. It is estimated that the new shutter would increase the epithermal neutron flux density by a factor of seven and the epithermal/fast neutron ratio by a factor of two. The modifications made to the BMRR in the past few years permit BNCT for brain tumors without the need to reflect scalp and bone flaps. Radiation workers are monitored via a TLD badge and a self-reading dosimeter during each experiment. An early concern was raised about whether workers would be subject to a significant dose rate from working with patients who have been irradiated. The gamma ray doses for the representative key personnel involved in the care of the first 12 patients receiving BNCT are listed. These workers did not receive unusually high exposures.

  20. Boron neutron capture therapy of brain tumors: past history, current status, and future potential.

    PubMed

    Barth, R F; Soloway, A H; Brugger, R M

    1996-01-01

    Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. High-grade astrocytomas, glioblastoma multiforme, and metastatic brain tumors constitute a major group of neoplasms for which there is no effective treatment. There is growing interest in using BNCT in combination with surgery to treat patients with primary, and possibly metastatic brain tumors. For BNCT to be successful, a large number of 10B atoms must be localized on or preferably within neoplastic cells, and a sufficient number of thermal neutrons must reach and be absorbed by the 10B atoms to sustain a lethal 10B(n, alpha)7 Li reaction. Two major questions will be addressed in this review. First, how can a large number of 10B atoms be delivered selectively to cancer cells? Second, how can a high fluence of neutrons be delivered to the tumor? Two boron compounds currently are being used clinically, sodium borocaptate (BSH) and boronophenylalanine (BPA), and a number of new delivery agents are under investigation, including boronated porphyrins, nucleosides, amino acids, polyamines, monoclonal and bispecific antibodies, liposomes, and epidermal growth factor. These will be discussed, and potential problems associated with their use as boron delivery agents will be considered. Nuclear reactors, currently, are the only source of neutrons for BNCT, and the fission process within the core produces a mixture of lower-energy thermal and epithermal neutrons, fast or high (> 10,000 eV) energy neutrons, and gamma rays. Although thermal neutron beams have been used clinically in Japan to treat patients with brain tumors and cutaneous melanomas, epithermal neutron beams should be more useful because of their superior tissue-penetrating properties. Beam sources and characteristics will be discussed in the context of current and future BNCT trials. Finally, the past and present

  1. Postmodernism and its application to the field of occupational therapy.

    PubMed

    Weinblatt, N; Avrech-Bar, M

    2001-06-01

    This article presents both the general concept of postmodernism and its reflection in a wide array of fields of interest. In particular, the paper reviews the postmodernist perspective as it appears in healthcare and medicine. This leads to a postmodernist analysis of the profession of occupational therapy, the main conclusion being that occupational therapy combines elements of modernism and postmodernism. This gives occupational therapy clinicians the luxury of enjoying the best of both worlds.

  2. NIFTI and DISCOS: New concepts for a compact accelerator neutron source for boron neutron capture therapy applications

    SciTech Connect

    Powell, J.; Ludewig, H.; Todosow, M.; Reich, M.

    1995-06-01

    Two new concepts, NIFTI and DISCOS, are described. These concepts enable the efficient production of epithermal neutrons for BNCT (Boron Neutron Capture Therapy) medical treatment, utilizing a low current, low energy proton beam impacting on a lithium target. The NIFTI concept uses fluoride compounds, such as lead or beryllium fluoride, to efficiently degrade high energy neutrons from the lithium target to the lower energies required for BNCT. The fluoride compounds are in turn encased in an iron layer that strongly impedes the transmission of neutrons with energies above 24 KeV. Lower energy neutrons readily pass through this iron filter, which has a deep window in its scattering cross section at 24 KeV. The DISCOS concept uses a rapidly rotating, high g disc to create a series of thin ({approximately} 1 micron thickness) liquid lithium targets in the form of continuous films or sheets of discrete droplets--through which the proton beam passes. The average energy lost by a proton as it passes through a single target is small, approximately 10 KeV. Between the targets, the proton beam is re-accelerated by an applied DC electric field. The DISCOS approach enables the accelerator--target facility to operate with a beam energy only slightly above the threshold value for neutron production--resulting in an output beam of low-energy epithermal neutrons--while achieving a high yield of neutrons per milliamp of proton beam current. Parametric trade studies of the NIFTI and DISCOS concepts are described. These include analyses of a broad range of NIFTI designs using the Monte carlo MCNP neutronics code, as well as mechanical and thermal-hydraulic analyses of various DISCOS designs.

  3. Chiral effective field theory predictions for muon capture on deuteron and $^3$He

    SciTech Connect

    Laura E. Marcucci, A. Kievsky, S. Rosati, R. Schiavilla, M. Viviani

    2012-01-01

    The muon-capture reactions {sup 2}H({mu}{sup -}, {nu}{sub {mu}})nn and {sup 3}He({mu}{sup -},{nu}{sub {mu}}){sup 3}H are studied with nuclear strong-interaction potentials and charge-changing weak currents, derived in chiral effective field theory. The low-energy constants (LEC's) c{sub D} and c{sub E}, present in the three-nucleon potential and (c{sub D}) axial-vector current, are constrained to reproduce the A=3 binding energies and the triton Gamow-Teller matrix element. The vector weak current is related to the isovector component of the electromagnetic current via the conserved-vector-current constraint, and the two LEC's entering the contact terms in the latter are constrained to reproduce the A=3 magnetic moments. The muon capture rates on deuteron and {sup 3}He are predicted to be 399 {+-} 3 sec{sup -1} and 1494 {+-} 21 sec{sup -1}, respectively, where the spread accounts for the cutoff sensitivity as well as uncertainties in the LEC's and electroweak radiative corrections. By comparing the calculated and precisely measured rates on {sup 3}He, a value for the induced pseudoscalar form factor is obtained in good agreement with the chiral perturbation theory prediction.

  4. Advances in analytical techniques for neutron capture therapy: thin layer chromatography matrix and track etch thin layer chromatography methods for boron-10 analysis

    SciTech Connect

    Schremmer, J.M.; Noonan, D.J.

    1987-09-01

    A new track etch autoradiographic technique for quantitating boron-10 containing compounds used for neutron capture therapy is described. Instead of applying solutions of Cs2B12H11SH and its oxidation products directly to solid-state nuclear track detectors, diethylaminoethyl cellulose thin layer chromatography (TLC) plates are utilized as sample matrices. The plates are juxtaposed with Lexan polycarbonate detectors and irradiated in a beam of thermal neutrons. The detectors are then chemically etched, and the resultant tracks counted with an optoelectronic image analyzer. Sensitivity to boron-10 in solution reaches the 1 pg/microliter level, or 1 ppb. In heparinized blood samples, 100 pg boron-10/microliter are detected. This TLC matrix method has the advantage that sample plates can be reanalyzed under different reactor conditions to optimize detector response to the boron-10 carrier material. Track etch/TLC allows quantitation of the purity of boron neutron capture therapy compounds by utilizing the above method with TLC plates developed in solvent systems that resolve Cs2B12H11SH and its oxidative analogs. Detectors irradiated in juxtaposition to the thin layer chromatograms are chemically etched, and the tracks are counted in the sample lane from the origin of the plate to the solvent front. A graphic depiction of the number of tracks per field yields a quantitative analysis of compound purity.

  5. Biomaterials and Magnetic fields for Cancer Therapy

    NASA Technical Reports Server (NTRS)

    Ramachandran, Narayanan; Mazuruk, Konstanty

    2003-01-01

    The field of biomaterials has emerged as an important topic in the purview of NASA s new vision of research activities in the Microgravity Research Division. Although this area has an extensive track record in the medical field as borne out by the routine use of polymeric sutures, implant devices, and prosthetics, novel applications such as tissue engineering, artificial heart valves and controlled drug delivery are beginning to be developed. Besides the medical field, biomaterials and bio-inspired technologies are finding use in a host of emerging interdisciplinary fields such as self-healing and self-assembling structures, biosensors, fuel systems etc. The field of magnetic fluid technology has several potential applications in medicine. One of the emerging fields is the area of controlled drug delivery, which has seen its evolution from the basic oral delivery system to pulmonary to transdermal to direct inoculations. In cancer treatment by chemotherapy for example, targeted and controlled drug delivery has received vast scrutiny and substantial research and development effort, due to the high potency of the drugs involved and the resulting requirement to keep the exposure of the drugs to surrounding healthy tissue to a minimum. The use of magnetic particles in conjunction with a static magnetic field allows smart targeting and retention of the particles at a desired site within the body with the material transport provided by blood perfusion. Once so located, the therapeutical aspect (radiation, chemotherapy, hyperthermia, etc.) of the treatment, now highly localized, can be implemented.

  6. A coupled deterministic/stochastic method for computing neutron capture therapy dose rates

    NASA Astrophysics Data System (ADS)

    Hubbard, Thomas Richard

    Neutron capture therapy (NCT) is an experimental method of treating brain tumors and other cancers by: (1) injecting or infusing the patient with a tumor-seeking, neutron target-labeled drug; and (2) irradiating the patient in an intense epithermal neutron fluence. The nuclear reaction between the neutrons and the target nuclei (e.g. sp{10}B(n,alpha)sp7Lirbrack releases energy in the form of high-LET (i.e. energy deposited within the range of a cell diameter) reaction particles which selectively kill the tumor cell. The efficacy of NCT is partly dependent on the delivery of maximum thermal neutron fluence to the tumor and the minimization of radiation dose to healthy tissue. Since the filtered neutron source (e.g. research reactor) usually provides a broad energy spectrum of highly-penetrating neutron and gamma-photon radiation, detailed transport calculations are necessary in order to plan treatments that use optimal treatment facility configurations and patient positioning. Current computational methods for NCT use either discrete ordinates calculation or, more often, Monte Carlo simulation to predict neutron fluences in the vicinity of the tumor. These methods do not, however, accurately calculate the transport of radiation throughout the entire facility or the deposition of dose in all the various parts of the body due to shortcomings of using either method alone. A computational method, specifically designed for NCT problems, has been adapted from the MASH methodology and couples a forward discrete ordinates (Ssb{n}) calculation with an adjoint Monte Carlo run to predict the dose at any point within the patient. The transport from the source through the filter/collimator is performed with a forward DORT run, and this is then coupled to adjoint MORSE results at a selected coupling parallelepiped which surrounds human phantom. Another routine was written to allow the user to generate the MORSE models at various angles and positions within the treatment room. The

  7. Boron-Containing Compounds for Liposome-Mediated Tumor Localization and Application to Neutron Capture Therapy

    SciTech Connect

    Hawthorne, M. Frederick

    2005-04-07

    Medical application of boron neutron capture therapy (BNCT) has been significantly hindered by the slow development of boron drug-targeting methodologies for the selective delivery of high boron concentration sto malignant cells. We have successfully sought to fill this need by creating liposomes suitable as in vivo boron delivery vehicles for BNCT. Delivery of therapeutic quantities of boron to tumors in murine models has been achieved with small unilamellar boron-rich liposomes. Subsequently, attempts have been made to improve delivery efficiency of liposomes encapsulating boron-containing water-soluble species into their hollow core by incorporating lipophilic boron compounds as addenda to the liposome bilayer, incorporating boron compounds as structural components of the bilayer (which however, poses the risk of sacrificing some stability), and combinations thereof. Regardless of the method, approximately 90% of the total liposome mass remains therapeutically inactive and comprised of the vehicle's construction materials, while less than 5% is boron for neutron targeting. Following this laboratory's intensive study, the observed tumor specificity of certain liposomes has been attributed to their diminutive size of these liposomes (30-150 nm), which enables these small vesicles to pass through the porous, immature vasculature of rapidly growing tumor tissue. We surmised that any amphiphilic nanoparticle of suitable size could possess some tumor selectivity. Consequently, the discovery of a very boron-rich nanoparticle delivery agent with biodistribution performance similar to unilamellar liposomes became one of our goals. Closomers, a new class of polyhedral borane derivatives, attracted us as an alternative BNCT drug-delivery system. We specifically envisioned dodeca (nido-carboranyl)-substituted closomers as possibly having a great potential role in BNCT drug delivery. They could function as extraordinarily boron-rich BNCT drugs since they are amphiphilic

  8. A theoretical model for the production of Ac-225 for cancer therapy by neutron capture transmutation of Ra-226.

    PubMed

    Melville, G; Melville, P

    2013-02-01

    Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation by bombarding Ra-226 with high-energy neutrons from a neutron source to produce Ra-225 and hence Ac-225, which can be used as a generator to produce Bi-213 for use in 'Targeted Alpha Therapy' for cancer. This paper examines the possibility of producing Ac-225 by neutron capture using a theoretical model in which neutron energy is convoluted with the corresponding neutron cross sections of Ra-226. The total integrated yield can then be obtained. This study shows that an intense beam of high-energy neutrons could initiate neutron capture on Ra-226 to produce Ra-225 and hence practical amounts of Ac-225 and a useful reduction of Ra-226.

  9. A rat model for the treatment of melanoma metastatic to the brain by means of neutron capture therapy

    SciTech Connect

    Matalka, K.Z.; Bailey, M.Q.; Barth, R.F.; Staubus, A.E.; Adams, D.M.; Soloway, A.H.; James, S.M.; Goodman, J.H. ); Coderre, J.A.; Fairchild, R.G. ); Rofstad, E.K. )

    1991-01-01

    Melanoma metastatic to the brain is a serious clinical problem for which there currently is no satisfactory treatment. Boron neutron capture therapy (BNCT) has been shown by Mishima et al. to be clinically effective in the treatment of cutaneous melanoma using {sup 10}B-enriched boronophenylalaine (BPA) as the capture agent. In the present pilot study we have observed a significant prolongation in survival time of nude rats bearing intracerebral implants of the human melanoma cell line MRA 27 following administration of BPA and neutron irradiation. These findings suggest therapeutic efficacy, but unequivocal proof depends upon confirmation in a more definitive experiment using large numbers of animals with both solitary and multiple implants of melanoma. If our preliminary results are confirmed, then this will lay the groundwork for a clinical study of BNCT for the treatment of melanoma metastatic to the brain. 7 refs., 2 figs., 2 tabs.

  10. Tumor growth suppression by gadolinium-neutron capture therapy using gadolinium-entrapped liposome as gadolinium delivery agent.

    PubMed

    Dewi, Novriana; Yanagie, Hironobu; Zhu, Haito; Demachi, Kazuyuki; Shinohara, Atsuko; Yokoyama, Kazuhito; Sekino, Masaki; Sakurai, Yuriko; Morishita, Yasuyuki; Iyomoto, Naoko; Nagasaki, Takeshi; Horiguchi, Yukichi; Nagasaki, Yukio; Nakajima, Jun; Ono, Minoru; Kakimi, Kazuhiro; Takahashi, Hiroyuki

    2013-07-01

    Neutron capture therapy (NCT) is a promising non-invasive cancer therapy approach and some recent NCT research has focused on using compounds containing gadolinium as an alternative to currently used boron-10 considering several advantages that gadolinium offers compared to those of boron. In this study, we evaluated gadolinium-entrapped liposome compound as neutron capture therapy agent by in vivo experiment on colon-26 tumor-bearing mice. Gadolinium compound were injected intravenously via tail vein and allowed to accumulate into tumor site. Tumor samples were taken for quantitative analysis by ICP-MS at 2, 12, and 24 h after gadolinium compound injection. Highest gadolinium concentration was observed at about 2 h after gadolinium compound injection with an average of 40.3 μg/g of wet tumor tissue. We performed neutron irradiation at JRR-4 reactor facility of Japan Atomic Energy Research Institute in Tokaimura with average neutron fluence of 2×10¹² n/cm². The experimental results showed that the tumor growth suppression of gadolinium-injected irradiated group was revealed until about four times higher compared to the control group, and no significant weight loss were observed after treatment suggesting low systemic toxicity of this compound. The gadolinium-entrapped liposome will become one of the candidates for Gd delivery system on NCT.

  11. Neutron capture therapy with deep tissue penetration using capillary neutron focusing

    DOEpatents

    Peurrung, Anthony J.

    1997-01-01

    An improved method for delivering thermal neutrons to a subsurface cancer or tumor which has been first doped with a dopant having a high cross section for neutron capture. The improvement is the use of a guide tube in cooperation with a capillary neutron focusing apparatus, or neutron focusing lens, for directing neutrons to the tumor, and thereby avoiding damage to surrounding tissue.

  12. A NEW SINGLE-CRYSTAL FILTERED THERMAL NEUTRON SOURCE FOR NEUTRON CAPTURE THERAPY RESEARCH AT THE UNIVERSITY OF MISSOURI

    SciTech Connect

    John D. Brockman; David W. Nigg; M. Frederick Hawthorne

    2008-09-01

    Parameter studies, design calculations and initial neutronic performance measurements have been completed for a new thermal neutron beamline to be used for neutron capture therapy cell and small-animal radiobiology studies at the University of Missouri Research Reactor. The beamline features the use of single-crystal silicon and bismuth sections for neutron filtering and for reduction of incident gamma radiation. The calculated and measured thermal neutron flux produced at the irradiation location is on the order of 9.5x108 neutrons/cm2-s, with a measured cadmium ratio (Au foils) of 105, indicating a well-thermalized spectrum.

  13. Initial Performance Characterization for a Thermalized Neutron Beam for Neutron Capture Therapy Research at Washington State University

    SciTech Connect

    David W. Nigg; P.E> Sloan; J.R. Venhuizen; C.A. Wemple

    2005-11-01

    The Idaho National Engineering and Environmental Laboratory (INEEL) and Washington State University (WSU) have constructed a new epithermal-neutron beam for collaborative Boron Neutron Capture Therapy (BNCT) preclinical research at the WSU TRIGATM research reactor facility1. More recently, additional beamline components were developed to permit the optional thermalization of the beam for certain types of studies where it is advantageous to use a thermal neutron source rather than an epithermal source. This article summarizes the results of some initial neutronic performance measurements for the thermalized system, with a comparison to the expected performance from the design computations.

  14. Dose-response analysis for boron neutron capture therapy of the B16 murine melanoma using p-boronophenylalanine

    SciTech Connect

    Coderre, J.A.; Micca, P.L.; Slatkin, D.N.; Makar, M.S.

    1990-01-01

    Boron Neutron Capture Therapy (BNCT) of a well-pigmented B16 melanoma implanted subcutaneously in the mouse thigh has been carried out at the Brookhaven Medical Research Reactor (BMRR) using the synthetic amino acid p-boronophenylalanine (BPA) as the boron delivery agent. The response of the B16 melanoma to BNCT was compared with the response to 250 kVp x-rays using both tumor growth delay and in vivo/in vitro assay that measures clonogenic survival. These experiments allow a comparison of tumor growth delay, log cell kill and damage to normal tissues produced by BNCT or photon irradiation.

  15. Molecular Medicine: Synthesis and In Vivo Detection of Agents for use in Boron Neutron Capture Therapy. Final Report

    SciTech Connect

    Kabalka, G. W.

    2005-06-28

    The primary objective of the project was the development of in vivo methods for the detection and evaluation of tumors in humans. The project was focused on utilizing positron emission tomography (PET) to monitor the distribution and pharamacokinetics of a current boron neutron capture therapy (BNCT) agent, p-boronophenylalanine (BPA) by labeling it with a fluorine-18, a positron emitting isotope. The PET data was then used to develop enhanced treatment planning protocols. The study also involved the synthesis of new tumor selective BNCTagents that could be labeled with radioactive nuclides for the in vivo detection of boron.

  16. Integration of real-time 3D capture, reconstruction, and light-field display

    NASA Astrophysics Data System (ADS)

    Zhang, Zhaoxing; Geng, Zheng; Li, Tuotuo; Pei, Renjing; Liu, Yongchun; Zhang, Xiao

    2015-03-01

    Effective integration of 3D acquisition, reconstruction (modeling) and display technologies into a seamless systems provides augmented experience of visualizing and analyzing real objects and scenes with realistic 3D sensation. Applications can be found in medical imaging, gaming, virtual or augmented reality and hybrid simulations. Although 3D acquisition, reconstruction, and display technologies have gained significant momentum in recent years, there seems a lack of attention on synergistically combining these components into a "end-to-end" 3D visualization system. We designed, built and tested an integrated 3D visualization system that is able to capture in real-time 3D light-field images, perform 3D reconstruction to build 3D model of the objects, and display the 3D model on a large autostereoscopic screen. In this article, we will present our system architecture and component designs, hardware/software implementations, and experimental results. We will elaborate on our recent progress on sparse camera array light-field 3D acquisition, real-time dense 3D reconstruction, and autostereoscopic multi-view 3D display. A prototype is finally presented with test results to illustrate the effectiveness of our proposed integrated 3D visualization system.

  17. Biological activity of N(4)-boronated derivatives of 2'-deoxycytidine, potential agents for boron-neutron capture therapy.

    PubMed

    Nizioł, Joanna; Uram, Łukasz; Szuster, Magdalena; Sekuła, Justyna; Ruman, Tomasz

    2015-10-01

    Boron-neutron capture therapy (BNCT) is a binary anticancer therapy that requires boron compound for nuclear reaction during which high energy alpha particles and lithium nuclei are formed. Unnatural, boron-containing nucleoside with hydrophobic pinacol moiety was investigated as a potential BNCT boron delivery agent. Biological properties of this compound are presented for the first time and prove that boron nucleoside has low cytotoxicity and that observed apoptotic effects suggest alteration of important functions of cancer cells. Mass spectrometry analysis of DNA from cancer cells proved that boron nucleoside is inserted into nucleic acids as a functional nucleotide derivative. NMR studies present very high degree of similarity of natural dG-dC base pair with dG-boron nucleoside system.

  18. Advances in boron neutron capture therapy (BNCT) at kyoto university - From reactor-based BNCT to accelerator-based BNCT

    NASA Astrophysics Data System (ADS)

    Sakurai, Yoshinori; Tanaka, Hiroki; Takata, Takushi; Fujimoto, Nozomi; Suzuki, Minoru; Masunaga, Shinichiro; Kinashi, Yuko; Kondo, Natsuko; Narabayashi, Masaru; Nakagawa, Yosuke; Watanabe, Tsubasa; Ono, Koji; Maruhashi, Akira

    2015-07-01

    At the Kyoto University Research Reactor Institute (KURRI), a clinical study of boron neutron capture therapy (BNCT) using a neutron irradiation facility installed at the research nuclear reactor has been regularly performed since February 1990. As of November 2014, 510 clinical irradiations were carried out using the reactor-based system. The world's first accelerator-based neutron irradiation system for BNCT clinical irradiation was completed at this institute in early 2009, and the clinical trial using this system was started in 2012. A shift of BCNT from special particle therapy to a general one is now in progress. To promote and support this shift, improvements to the irradiation system, as well as its preparation, and improvements in the physical engineering and the medical physics processes, such as dosimetry systems and quality assurance programs, must be considered. The recent advances in BNCT at KURRI are reported here with a focus on physical engineering and medical physics topics.

  19. Boron neutron capture therapy for the treatment of cerebral gliomas. I. Theoretical evaluation of the efficacy of various neutron beams.

    PubMed

    Zamenhof, R G; Murray, B W; Brownell, G L; Wellum, G R; Tolpin, E I

    1975-01-01

    The technique of boron neutron capture therapy in the treatment of cerebral gliomas depends upon the selective loading of the tumor with a 10B-enriched compound and subsequent irradiation of the brain with low-energy neutrons. The charged particles produced in the 10B (n,alpha) 7Li reaction have ranges in tissue of less than 10 mum so that the dose distribution closely follows the 10B distribution even to the cellular level. The effectiveness of this therapy procedure is dependent not only on the 10B compound but on the spectral characteristics of the neutron source as well. Hence, an optimization of these characteristics will increase the chances of therapeutic success. Transport calculations using a neutral particle transport code have been made to determine the dose-depth distributions within a simple head phantom for five different incident neutron beams. Comparison of these beams to determine their relative therapeutic efficacy was made by the use of a maximum useable depth criterion. In particular, with presently available compounds, the MIT reactor (MITR) therapy beam (a) is not inferior to a pure thermal neutron beam, (b) would be marginally improved if its gamma-ray contamination were eliminated, (c) is superior to a partially 10B-filtered MITR beam, and (d) produces a maximum useable depth which is strongly dependent upon the tumor-to-blood ratio of 10B concentrations and weakly dependent upon the absolute 10B concentration in tumor. A pure epithermal neutron beam with a mean energy of 37 eV is shown to have close to the optimal characteristics for boron neutron capture therapy. Futhermore, these optimal characteristics can be approximated by a judiciously D2O moderated and 10B-filtered 252Cf neutron source. This tailored 252Cf source would have at least a 1.5 cm greater maximum useable depth than the MITR therapy beam for realistic 10B concentrations. However, at least one gram of 252Cf would be needed to make this a practical therapy source. If the

  20. Electric field controlled CO2 capture and CO2/N2 separation on MoS2 monolayers.

    PubMed

    Sun, Qiao; Qin, Gangqiang; Ma, Yingying; Wang, Weihua; Li, Ping; Du, Aijun; Li, Zhen

    2017-01-07

    Developing new materials and technologies for efficient CO2 capture, particularly for separation of CO2 post-combustion, will significantly reduce the CO2 concentration and its impacts on the environment. A challenge for CO2 capture is to obtain high performance adsorbents with both high selectivity and easy regeneration. Here, CO2 capture/regeneration on MoS2 monolayers controlled by turning on/off external electric fields is comprehensively investigated through a density functional theory calculation. The calculated results indicate that CO2 forms a weak interaction with MoS2 monolayers in the absence of an electric field, but strongly interacts with MoS2 monolayers when an electric field of 0.004 a.u. is applied. Moreover, the adsorbed CO2 can be released from the surface of MoS2 without any energy barrier once the electric field is turned off. Compared with the adsorption of CO2, the interactions between N2 and MoS2 are not affected significantly by the external electric fields, which indicates that MoS2 monolayers can be used as a robust absorbent for controllable capture of CO2 by applying an electric field, especially to separate CO2 from the post-combustion gas mixture where CO2 and N2 are the main components.

  1. Neutron capture therapy with deep tissue penetration using capillary neutron focusing

    DOEpatents

    Peurrung, A.J.

    1997-08-19

    An improved method is disclosed for delivering thermal neutrons to a subsurface cancer or tumor which has been first doped with a dopant having a high cross section for neutron capture. The improvement is the use of a guide tube in cooperation with a capillary neutron focusing apparatus, or neutron focusing lens, for directing neutrons to the tumor, and thereby avoiding damage to surrounding tissue. 1 fig.

  2. Experimental Transport Benchmarks for Physical Dosimetry to Support Development of Fast-Neutron Therapy with Neutron Capture Augmentation

    SciTech Connect

    D. W. Nigg; J. K. Hartwell; J. R. Venhuizen; C. A. Wemple; R. Risler; G. E. Laramore; W. Sauerwein; G. Hudepohl; A. Lennox

    2006-06-01

    The Idaho National Laboratory (INL), the University of Washington (UW) Neutron Therapy Center, the University of Essen (Germany) Neutron Therapy Clinic, and the Northern Illinois University(NIU) Institute for Neutron Therapy at Fermilab have been collaborating in the development of fast-neutron therapy (FNT) with concurrent neutron capture (NCT) augmentation [1,2]. As part of this effort, we have conducted measurements to produce suitable benchmark data as an aid in validation of advanced three-dimensional treatment planning methodologies required for successful administration of FNT/NCT. Free-beam spectral measurements as well as phantom measurements with Lucite{trademark} cylinders using thermal, resonance, and threshold activation foil techniques have now been completed at all three clinical accelerator facilities. The same protocol was used for all measurements to facilitate intercomparison of data. The results will be useful for further detailed characterization of the neutron beams of interest as well as for validation of various charged particle and neutron transport codes and methodologies for FNT/NCT computational dosimetry, such as MCNP [3], LAHET [4], and MINERVA [5].

  3. Development of high boron content liposomes and their promising antitumor effect for neutron capture therapy of cancers.

    PubMed

    Koganei, Hayato; Ueno, Manabu; Tachikawa, Shoji; Tasaki, Lisa; Ban, Hyun Seung; Suzuki, Minoru; Shiraishi, Kouichi; Kawano, Kumi; Yokoyama, Masayuki; Maitani, Yoshie; Ono, Koji; Nakamura, Hiroyuki

    2013-01-16

    Mercaptoundecahydrododecaborate (BSH)-encapsulating 10% distearoyl boron lipid (DSBL) liposomes were developed as a boron delivery vehicle for neutron capture therapy. The current approach is unique because the liposome shell itself possesses cytocidal potential in addition to its encapsulated agents. BSH-encapsulating 10% DSBL liposomes have high boron content (B/P ratio: 2.6) that enables us to prepare liposome solution with 5000 ppm boron concentration. BSH-encapsulating 10% DSBL liposomes displayed excellent boron delivery efficacy to tumor: boron concentrations reached 174, 93, and 32 ppm at doses of 50, 30, and 15 mg B/kg, respectively. Magnescope was also encapsulated in the 10% DSBL liposomes and the real-time biodistribution of the Magnescope-encapsulating DSBL liposomes was measured in a living body using MRI. Significant antitumor effect was observed in mice injected with BSH-encapsulating 10% DSBL liposomes even at the dose of 15 mg B/kg; the tumor completely disappeared three weeks after thermal neutron irradiation ((1.5-1.8) × 10(12) neutrons/cm(2)). The current results enabled us to reduce the total dose of liposomes to less than one-fifth compared with that of the BSH-encapsulating liposomes without reducing the efficacy of boron neutron capture therapy (BNCT).

  4. Synthesis and biological evaluation of new boron-containing chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

    PubMed

    Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

    2014-03-01

    New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were investigated in tumor-bearing mice. The time to maximum accumulation of compound 13 in tumor tissue was one-fourth of that of compound 9, and compound 13 showed rapid clearance from normal tissues within 24h after injection. The in vivo therapeutic efficacy of PDT using 13 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3h after injection of 13. Tumor growth was significantly inhibited by PDT using 13. These results suggested that 13 might be a good candidate for both PDT and BNCT of cancer.

  5. A military grade, field usable, Raman analyzer: measurement of captured fuel

    NASA Astrophysics Data System (ADS)

    Farquharson, Stuart; Smith, Wayne; Shende, Chetan; Patient, Michael; Huang, Hermes; Brouillette, Carl

    2014-05-01

    Portable Raman analyzers have emerged during the first part of this century as an important field tool for crime scene and forensic analysis, primarily for their ability to identify unknown substances. This ability is also important to the US military, which has been investigating such analyzers for identification of explosive materials that may be used to produce improvised explosive devices, chemicals that may be used to produce chemical warfare agents, and fuels in storage tanks that may be used to power US military vehicles. However, the use of such portable analyzers requires that they meet stringent military standards (specifically MIL-STD 810G). These requirements include among others: 1) light weight and small size (< 35 pounds, < 3 cu. ft.), 2) vibration and shock resistant (26 four foot drops), 3) operation from -4 to 110 oF, 4) operation in blowing dust, sand and rain, 5) battery operation, and of course 6) safe operation (no laser or shock hazards). Here we describe a portable Raman analyzer that meets all of these requirements, and its use to determine if captured fuels are suitable for use.

  6. Studies for the application of boron neutron capture therapy to the treatment of differentiated thyroid cancer.

    PubMed

    Dagrosa, A; Carpano, M; Perona, M; Thomasz, L; Nievas, S; Cabrini, R; Juvenal, G; Pisarev, M

    2011-12-01

    The aim of these studies was to evaluate the possibility of treating differentiated thyroid cancer by BNCT. These carcinomas are well controlled with surgery followed by therapy with (131)I; however, some patients do not respond to this treatment. BPA uptake was analyzed both in vitro and in nude mice implanted with cell lines of differentiated thyroid carcinoma. The boron intracellular concentration in the different cell lines and the biodistribution studies showed the selectivity of the BPA uptake by this kind of tumor.

  7. Improved monitoring system of neutron flux during boron-neutron capture therapy

    SciTech Connect

    Harasawa, S.; Nakamoto, A.; Hayakawa, Y.; Egawa, J.

    1981-10-01

    Continuous and simultaneous monitoring of neutron flux in the course of a boron-neutron capture operation on a brain tumor has been achieved using a new monitoring system. A silicon surface barrier diode mounted with /sup 6/LiF instead of the previously reported borax is used to sense neutrons. The pulse heights of /sup 3/H and ..cap alpha.. particles from /sup 6/Li(n, ..cap alpha..)/sup 2/H reaction are sufficiently high and well separated from noises due to ..gamma.. rays. The effect of pulse-height reduction due to the radiation damage of the diode thus becomes smaller, permitting continuous monitoring. The relative error of the monitoring is within 2% over 5 hr for a neutron-flux density of 2 x 10/sup 9/ n/cm/sup 2/ sec.

  8. Nuclear magnetic resonance study of Gd-based nanoparticles to tag boron compounds in boron neutron capture therapy

    SciTech Connect

    Corti, M.; Bonora, M.; Borsa, F.; Bortolussi, S.; Protti, N.; Santoro, D.; Stella, S.; Altieri, S.; Zonta, C.; Clerici, A. M.; Cansolino, L.; Ferrari, C.; Dionigi, P.; Porta, A.; Zanoni, G.; Vidari, G.

    2011-04-01

    We report the investigation of new organic complexes containing a magnetic moment (Gd-based molecular nanomagnets), which can serve the double purpose of acting as boron neutron capture therapy (BNCT) agents, and at the same time act as contrast agents to detect the molecule in the tissue by a proton magnetic resonance imaging (MRI). We also explore the possibility of monitoring the concentration of the BNCT agent directly via proton and boron NMR relaxation. The absorption of {sup 10}B-enriched molecules inside tumoral liver tissues has been shown by NMR measurements and confirmed by {alpha} spectroscopy. A new molecular Gd-tagged nanomagnet and BNCT agent (GdBPA) has been synthesized and characterized measuring its relaxivity R{sub 1} between 10 kHz and 66 MHz, and its use as a contrast agent in MRI has been demonstrated. The NMR-based evidence of the absorption of GdBPA into living tumoral cells is also shown.

  9. IMPROVED COMPUTATIONAL CHARACTERIZATION OF THE THERMAL NEUTRON SOURCE FOR NEUTRON CAPTURE THERAPY RESEARCH AT THE UNIVERSITY OF MISSOURI

    SciTech Connect

    Stuart R. Slattery; David W. Nigg; John D. Brockman; M. Frederick Hawthorne

    2010-05-01

    Parameter studies, design calculations and initial neutronic performance measurements have been completed for a new thermal neutron beamline to be used for neutron capture therapy cell and small-animal radiobiology studies at the University of Missouri Research Reactor. The beamline features the use of single-crystal silicon and bismuth sections for neutron filtering and for reduction of incident gamma radiation. The computational models used for the final beam design and performance evaluation are based on coupled discrete-ordinates and Monte Carlo techniques that permit detailed modeling of the neutron transmission properties of the filtering crystals with very few approximations. This is essential for detailed dosimetric studies required for the anticipated research program.

  10. Experimental and Simulated Characterization of a Beam Shaping Assembly for Accelerator- Based Boron Neutron Capture Therapy (AB-BNCT)

    SciTech Connect

    Burlon, Alejandro A.; Valda, Alejandro A.; Girola, Santiago; Minsky, Daniel M.; Kreiner, Andres J.

    2010-08-04

    In the frame of the construction of a Tandem Electrostatic Quadrupole Accelerator facility devoted to the Accelerator-Based Boron Neutron Capture Therapy, a Beam Shaping Assembly has been characterized by means of Monte-Carlo simulations and measurements. The neutrons were generated via the {sup 7}Li(p, n){sup 7}Be reaction by irradiating a thick LiF target with a 2.3 MeV proton beam delivered by the TANDAR accelerator at CNEA. The emerging neutron flux was measured by means of activation foils while the beam quality and directionality was evaluated by means of Monte Carlo simulations. The parameters show compliance with those suggested by IAEA. Finally, an improvement adding a beam collimator has been evaluated.

  11. A Small-Animal Irradiation Facility for Neutron Capture Therapy Research at the RA-3 Research Reactor

    SciTech Connect

    Emiliano Pozzi; David W. Nigg; Marcelo Miller; Silvia I. Thorp; Amanda E. Schwint; Elisa M. Heber; Veronica A. Trivillin; Leandro Zarza; Guillermo Estryk

    2007-11-01

    The National Atomic Energy Commission of Argentina (CNEA) has constructed a thermal neutron source for use in Boron Neutron Capture Therapy (BNCT) applications at the RA-3 research reactor facility located in Buenos Aires. The Idaho National Laboratory (INL) and CNEA have jointly conducted some initial neutronic characterization measurements for one particular configuration of this source. The RA-3 reactor (Figure 1) is an open pool type reactor, with 20% enriched uranium plate-type fuel and light water coolant. A graphite thermal column is situated on one side of the reactor as shown. A tunnel penetrating the graphite structure enables the insertion of samples while the reactor is in normal operation. Samples up to 14 cm height and 15 cm width are accommodated.

  12. The effect of pulsed electromagnetic field therapy on food sensitivity.

    PubMed

    Monro, Jean A; Puri, Basant K

    2015-01-01

    Owing to the involvement of the immune system in the etiology of food sensitivity, and because pulsed electromagnetic field therapy is associated with beneficial immunologic changes, it was hypothesized that pulsed electromagnetic fields may have a beneficial effect on food sensitivity. A small pilot study was carried out in patients suffering from food sensitivity, with the antigen leukocyte antibody test being employed to index the degree of food sensitivity in terms of the number of foods to which each patient reacted. It was found that a 1-week course of pulsed electromagnetic field therapy, consisting of one hour's treatment per day, resulted in a reduction in the mean number of reactive foods of 10.75 (p < 0.05). On the basis of these results, a larger study is warranted.

  13. Dose point kernel for boron-11 decay and the cellular S values in boron neutron capture therapy.

    PubMed

    Ma, Yunzhi; Geng, JinPeng; Gao, Song; Bao, Shanglian

    2006-12-01

    The study of the radiobiology of boron neutron capture therapy is based on the cellular level dosimetry of boron-10's thermal neutron capture reaction 10B(n,alpha)7Li, in which one 1.47 MeV helium-4 ion and one 0.84 MeV lithium-7 ion are spawned. Because of the chemical preference of boron-10 carrier molecules, the dose is heterogeneously distributed in cells. In the present work, the (scaled) dose point kernel of boron-11 decay, called 11B-DPK, was calculated by GEANT4 Monte Carlo simulation code. The DPK curve drops suddenly at the radius of 4.26 microm, the continuous slowing down approximation (CSDA) range of a lithium-7 ion. Then, after a slight ascending, the curve decreases to near zero when the radius goes beyond 8.20 microm, which is the CSDA range of a 1.47 MeV helium-4 ion. With the DPK data, S values for nuclei and cells with the boron-10 on the cell surface are calculated for different combinations of cell and nucleus sizes. The S value for a cell radius of 10 microm and a nucleus radius of 5 microm is slightly larger than the value published by Tung et al. [Appl. Radiat. Isot. 61, 739-743 (2004)]. This result is potentially more accurate than the published value since it includes the contribution of a lithium-7 ion as well as the alpha particle.

  14. Dosimetry and stability studies of the boron neutron capture therapy agent F-BPA-Fr using PET and MRI

    NASA Astrophysics Data System (ADS)

    Dyke, Jonathan Paul

    The treatment of deep seated brain tumors such as glioblastoma Multiforme has been unsuccessful for many patients. Surgical debulking, chemotherapy and standard radiotherapy have met with limited success. Boron neutron capture therapy offers a binary mode brachytherapy based on the following capture reaction that may provide an innovative alternative to standard forms of treatment:10B + n /to/ 11B /to 7Li + 4He + 2.31 MeVBoron is chemically attached to a tumor binding compound creating a non-toxic neutron absorber. A dose of epithermal neutrons provides the catalyst to produce the lithium and alpha particles which destroy any tissue within a length of one cell diameter from the boron compound. This dissertation uses 19F-MRI and 18F-PET to provide answers to the localization and biodistribution questions that arise in such a treatment modality. Practical patient dosimetry and actual treatment planning using the PET data is also examined. Finally, theoretical work done in the areas of compartmental modelling dealing with pharmacokinetic uptake of the PET radiotracer and dose analysis in microdosimetry is also presented.

  15. Treatment of isografted 9L rat brain tumors with beta-5-o-carboranyl-2'-deoxyuridine neutron capture therapy.

    PubMed

    Schinazi, R F; Hurwitz, S J; Liberman, I; Juodawlkis, A S; Tharnish, P; Shi, J; Liotta, D C; Coderre, J A; Olson, J

    2000-02-01

    beta-5-o-Carboranyl-2'-deoxyuridine (D-CDU) is a nontoxic pyrimidine nucleoside analogue designed for boron neutron capture therapy of brain tumors. In vitro studies indicated that D-CDU accumulates to levels 92- and 117-fold higher than the extracellular concentration in rat 9L and human U-251 glioma cells, respectively, and persists for several hours at levels 5-fold higher than the extracellular concentration. Furthermore, D-CDU was not toxic to rats injected i.p. with up to 150 mg/kg. On the basis of these studies, D-CDU was evaluated as a neutron capture therapy agent using rats bearing stereotactically implanted intracranial 9L tumors at single i.p. doses of 30 mg/kg and 150 mg/kg of D-CDU (20% 10B enriched), given 2 h before irradiation with thermal neutrons. Boron concentrations in tumors 2 h after dosing were 2.3 +/- 1.6 and 7.4 +/- 1.3 micrograms boron/g tissue (mean +/- SD), corresponding to tumor/brain ratios of 11.5 +/- 3.6 and 6.8 +/- 2.0 micrograms boron/g tissue for the low and high doses, respectively. All untreated animals died within 28 days, whereas half survived at days 32, 55, and 38 for groups receiving neutrons only, 30 mg/kg D-CDU, and 150 mg/kg D-CDU, respectively. Odds ratios of all treatment groups differed significantly from the untreated group (P < 0.002; logrank test). The median survival time for the 30 mg/kg-treated group but not for the 150 mg/kg-treated group was significantly longer than for rats treated with neutrons only (P = 0.036), which may correlate with the decreased tumor selectivity for D-CDU observed at the higher dose. Additional pharmacodynamic studies are warranted to determine optimal dosing strategies for D-CDU.

  16. A Bystander Effect Observed in Boron Neutron Capture Therapy: A Study of the Induction of Mutations in the HPRT Locus

    SciTech Connect

    Kinashi, Yuko . E-mail: kinashi@rri.kyoto-u.ac.jp; Masunaga, Shinichiro; Nagata, Kenji; Suzuki, Minoru; Takahashi, Sentaro; Ono, Koji

    2007-06-01

    Purpose: To investigate bystander mutagenic effects induced by {alpha}-particles during boron neutron capture therapy, we mixed cells that were electroporated with borocaptate sodium (BSH), which led to the accumulation of {sup 10}B inside the cells, and cells that did not contain the boron compound. The BSH-containing cells were irradiated with {alpha}-particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction, whereas cells without boron were affected only by the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. Methods and Materials: The lethality and mutagenicity measured by the frequency of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase locus were examined in Chinese hamster ovary cells irradiated with neutrons (Kyoto University Research Reactor: 5 MW). Neutron irradiation of 1:1 mixtures of cells with and without BSH resulted in a survival fraction of 0.1, and the cells that did not contain BSH made up 99.4% of the resulting cell population. The molecular structures of the mutations were determined using multiplex polymerase chain reactions. Results: Because of the bystander effect, the frequency of mutations increased in the cells located nearby the BSH-containing cells compared with control cells. Molecular structural analysis indicated that most of the mutations induced by the bystander effect were point mutations and that the frequencies of total and partial deletions induced by the bystander effect were less than those induced by the original neutron irradiation. Conclusion: These results suggested that in boron neutron capture therapy, the mutations caused by the bystander effect and those caused by the original neutron irradiation are induced by different mechanisms.

  17. An aquatic light trap designed for live capture of predatory Tropisternus sp (Coleoptera: Hydrophilidae) larvae in Arkansas rice fields.

    PubMed

    Dennett, J A; Meisch, M V

    2001-12-01

    Construction of an aquatic light trap developed for the live capture of 3rd-stage larvae of predatory Tropisternus sp. for use in laboratory bioassays against larvae of Anopheles quadrimaculatus and Psorophora columbiae is described. On 10 occasions, an average of 5.2 traps was used per evening, resulting in 52 trap-nights that accumulated 106.7 h of trapping time, or an average of 10.6 h per trap. Use of 2 heavy-duty alkaline D-sized batteries and appropriate in-circuit resistance effectively increased bulb life and trap operating time, ranging from 22 to 36 h. During both seasons, approximately 3 wk after permanent flooding of large rice fields was the most productive period in which to capture larvae of Tropisternus sp. Live trapping worked well and provided numerous larvae of Tropisternus sp. for use in laboratory predation bioassays with An. quadrimaculatus and Ps. columbiae larvae. Six hundred fifteen 3rd-stage larvae of Tropisternus sp. and 740 adult Tropisternus lateralis were captured in aquatic light traps in 1999 and 2000. Of traps containing larval Tropisternus sp. and adult T. lateralis, average numbers of 15.3 and 19.4 were captured per trap, respectively. Among all traps, the largest nightly captures of larval Tropisternus sp. and adult T. lateralis consisted of 263 and 404 specimens, respectively. The largest single trap captures for larval Tropisternus sp. and adult T. lateralis were 94 and 184, respectively. Additionally, 478 rice water weevils (Lissorhoptrus oryzophilus) also were captured. Rice water weevils averaged 36.7 per trap, with the largest single trap capture of 102 weevils on an evening where 287 weevils were captured among all traps. Other predatory insect species were captured infrequently, consisting primarily of 3rd-stage larvae of Hydrophilus triangularis and adult belostomatids, dytiscids, and notonectids. Predatory larvae of H. triangularis may have been attracted to the traps by the presence of larval Tropisternus sp. Larval

  18. Gadolinium dosimetry, a problematic issue in the neutron capture therapy. Comparison between experiments and computational simulations.

    NASA Astrophysics Data System (ADS)

    Bufalino, D.; Cerullo, N.; Colli, V.; Gambarini, G.; Rosi, G.

    2006-05-01

    In GdNCT the interested isotope is 157Gd that captures neutrons with (n, ) reaction and also emits internal conversion and Auger electrons. These electrons have an important effect on DNA strands, mainly due to the property of gadolinium to link to DNA. The emitted gamma rays partially interacts with tumours but mainly diffuse in the body damaging healthy tissues. Therefore in the study of Gd therapeutical effect both dosimetric and microdosimetric analyses must be performed. At Pisa University, in the last years some works were performed by NCT group. At the present these researches are continued on these topics carrying out also a PhD thesis. In this frame some simulations, using MC code, were performed in order to evaluate the dose distribution due to Gd reactions. It is however necessary to calibrate the calculations on experimental results, though they are scarce in GdNCT. Some experiments with 157Gd were performed by Milan group using gel dosimetry [1, 2, 3]. Therefore some computational comparisons were done. In these article the results of this comparisons are shown and discussed.

  19. Early history of development of boron neutron capture therapy of tumors.

    PubMed

    Sweet, W H

    1997-05-01

    The stable isotope 10B has a peculiarly marked avidity to capture slow neutrons whereupon it disintegrates into a lithium and a helium atom. These give up the 2.4 MeV of disintegration energy which they share within 5 and 9 microns of the 10B atom respectively. This means that the cell closest to the 10B atom bears the brunt of its atomic explosion. The objective of the tumor therapist is to find a carrier molecule for the boron atom which will concentrate in the tumor. Although a number of investigators saw the peculiar advantage of this selective tactic to achieve destruction of a species of unwanted cells, no success in animal studies was achieved until 1950. Sweet and colleagues found that the capillary blood-brain barrier keeps many substances out of the normal brain but that the gliomas had much less of such a barrier. He, Brownell, Soloway and Hatanaka in Boston together with Farr. Godwin, Robertson, Stickley. Konikowski and others at the Brookhaven. National Laboratory worked partially in collaboration and partly independently. We irradiated at 3 nuclear reactors several series of glioma patients with no long-term remission, much less a cure being achieved. Hatanaka on his return to Japan kept BNCT alive by treating a total of 140 patients with various brain tumors. Beginning in 1972, Mishima and colleagues have achieved useful concentrations of 10B-borono-phenylalanine, an analogue of the melanin precursor tyrosine, for BNCT of melanomas.

  20. Development of a dual phantom technique for measuring the fast neutron component of dose in boron neutron capture therapy

    SciTech Connect

    Sakurai, Yoshinori Tanaka, Hiroki; Kondo, Natsuko; Kinashi, Yuko; Suzuki, Minoru; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira

    2015-11-15

    Purpose: Research and development of various accelerator-based irradiation systems for boron neutron capture therapy (BNCT) is underway throughout the world. Many of these systems are nearing or have started clinical trials. Before the start of treatment with BNCT, the relative biological effectiveness (RBE) for the fast neutrons (over 10 keV) incident to the irradiation field must be estimated. Measurements of RBE are typically performed by biological experiments with a phantom. Although the dose deposition due to secondary gamma rays is dominant, the relative contributions of thermal neutrons (below 0.5 eV) and fast neutrons are virtually equivalent under typical irradiation conditions in a water and/or acrylic phantom. Uniform contributions to the dose deposited from thermal and fast neutrons are based in part on relatively inaccurate dose information for fast neutrons. This study sought to improve the accuracy in the dose estimation for fast neutrons by using two phantoms made of different materials in which the dose components can be separated according to differences in the interaction cross sections. The development of a “dual phantom technique” for measuring the fast neutron component of dose is reported. Methods: One phantom was filled with pure water. The other phantom was filled with a water solution of lithium hydroxide (LiOH) capitalizing on the absorbing characteristics of lithium-6 (Li-6) for thermal neutrons. Monte Carlo simulations were used to determine the ideal mixing ratio of Li-6 in LiOH solution. Changes in the depth dose distributions for each respective dose component along the central beam axis were used to assess the LiOH concentration at the 0, 0.001, 0.01, 0.1, 1, and 10 wt. % levels. Simulations were also performed with the phantom filled with 10 wt. % {sup 6}LiOH solution for 95%-enriched Li-6. A phantom was constructed containing 10 wt. % {sup 6}LiOH solution based on the simulation results. Experimental characterization of the

  1. Boron Neutron Capture Therapy for HER2+ breast cancers: A feasibility study evaluating BNCT for potential role in breast conservation therapies

    NASA Astrophysics Data System (ADS)

    Jenkins, Peter Anthony

    A novel Boron Neutron Capture Therapy (BNCT) regimen for the treatment of HER2+ breast cancers has been proposed as an alternative to whole breast irradiation for breast conservation therapy patients. The proposed therapy regimen is based on the assumed production of boron delivery agents that would be synthesized from compounds of Trastuzumab (Herceptin ®) and oligomeric phosphate diesters (OPDs). The combination of the anti-HER2 monoclonal antibody and the high boron loading capability of OPDs has led to the assumption that boron could be delivered to the HER2+ cancer cells at Tumor to Healthy Tissue ratios (T:H) of up to 35:1 and boron concentrations above 50 μg/g. This significantly increased boron delivery efficiency has opened new BNCT possibilities. This proof of concept study examined treatment parameters derived as the results in previous efforts in the context of patient-specific geometry and compared calculated dose results to those observed during actual patient therapy. These results were based on dose calculations performed with a set of calculated Kerma coefficients derived from tissues specific to the regions of interest for breast cancer. A comparison was made of the dose to the tumor region, the patient's skin, and the peripheral organs. The results of this study demonstrated that, given the performance of the proposed boron delivery agent, the BNCT treatment regimen is feasible. The feasibility is based on the findings that the equivalent dose could be delivered to the treatment volume with less dose to the skin and peripheral organs. This is anticipated to improve the treatment outcomes by maintaining local control of tumor cells while reducing dose to healthy tissues.

  2. L-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

    SciTech Connect

    Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna; Vaelimaeki, Petteri; Beule, Annette; Collan, Juhani; Kortesniemi, Mika; Uusi-Simola, Jouni; Kotiluoto, Petri; Auterinen, Iiro; Seren, Tom; Paetau, Anders; Saarilahti, Kauko; Savolainen, Sauli; Joensuu, Heikki

    2011-06-01

    Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, either 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an L-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.

  3. Extended-field radiation therapy for carcinoma of the cervix

    SciTech Connect

    Podczaski, E.; Stryker, J.A.; Kaminski, P.; Ndubisi, B.; Larson, J.; DeGeest, K.; Sorosky, J.; Mortel, R. )

    1990-07-15

    The survival of cervical carcinoma patients with paraaortic/high common iliac nodal metastases was evaluated by retrospective chart review during a 13-year interval. Thirty-three patients with cervical carcinoma and surgically documented nodal metastases received primary, extended-field radiation therapy. Overall 2-year and 5-year actuarial survival rates after diagnosis were 37% and 31%, respectively. Survival was analyzed in terms of the variables patient age, clinical stage, tumor histologic type, the presence of enlarged paraaortic/high common iliac lymph nodes, the extent of nodal involvement (microscopic versus macroscopic), the presence of intraperitoneal disease, and whether intracavitary brachytherapy was administered. The use of intracavitary radiation therapy was associated with improved local control and survival (P = 0.017). None of the other variables were statistically related to patient survival. Twenty-two of the patients died of cervical cancer and five are surviving without evidence of cancer. Four patients died of intercurrent disease. Two patients developed bowel-related radiation complications; both patients received chemotherapy concurrent with the radiation therapy. One of the two patients died of radiation enteritis. The use of extended-field radiation therapy does benefit a small group of patients and may result in extended patient survival.

  4. The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide.

    PubMed

    Michiue, Hiroyuki; Sakurai, Yoshinori; Kondo, Natsuko; Kitamatsu, Mizuki; Bin, Feng; Nakajima, Kiichiro; Hirota, Yuki; Kawabata, Shinji; Nishiki, Tei-ichi; Ohmori, Iori; Tomizawa, Kazuhito; Miyatake, Shin-ichi; Ono, Koji; Matsui, Hideki

    2014-03-01

    New anti-cancer therapy with boron neutron capture therapy (BNCT) is based on the nuclear reaction of boron-10 with neutron irradiation. The median survival of BNCT patients with glioblastoma was almost twice as long as those receiving standard therapy in a Japanese BNCT clinical trial. In this clinical trial, two boron compounds, BPA (boronophenylalanine) and BSH (sodium borocaptate), were used for BNCT. BPA is taken up into cells through amino acid transporters that are expressed highly in almost all malignant cells, but BSH cannot pass through the cell membrane and remains outside the cell. We simulated the energy transfer against the nucleus at different locations of boron from outside the cell to the nuclear region with neutron irradiation and concluded that there was a marked difference between inside and outside the cell in boron localization. To overcome this disadvantage of BSH in BNCT, we used a cell-penetrating peptide system for transduction of BSH. CPP (cell-membrane penetrating peptide) is very common peptide domains that transduce many physiologically active substances into cells in vitro and in vivo. BSH-fused CPPs can penetrate the cell membrane and localize inside a cell. To increase the boron ratio in one BSH-peptide molecule, 8BSH fused to 11R with a dendritic lysine structure was synthesized and administrated to malignant glioma cells and a brain tumor mouse model. 8BSH-11R localized at the cell nucleus and showed a very high boron value in ICP results. With neutron irradiation, the 8BSH-11R administrated group showed a significant cancer killing effect compared to the 100 times higher concentration of BSH-administrated group. We concluded that BSH-fused CPPs were one of the most improved and potential boron compounds in the next-stage BNCT trial and 8BSH-11R may be applied in the clinical setting.

  5. Field Test Results of Using a Nacelle-Mounted Lidar for Improving Wind Energy Capture by Reducing Yaw Misalignment (Presentation)

    SciTech Connect

    Fleming, P.; Scholbrock, A.; Wright, A.

    2014-11-01

    Presented at the Nordic Wind Power Conference on November 5, 2014. This presentation describes field-test campaigns performed at the National Wind Technology Center in which lidar technology was used to improve the yaw alignment of the Controls Advanced Research Turbine (CART) 2 and CART3 wind turbines. The campaigns demonstrated that whether by learning a correction function to the nacelle vane, or by controlling yaw directly with the lidar signal, a significant improvement in power capture was demonstrated.

  6. Synthesis and biological evaluation of new BSH-conjugated chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

    PubMed

    Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

    2014-11-01

    New disodium mercaptoundecahydro-closo-dodecaborate (BSH)-conjugated chlorin derivatives 11, 12, 16 and 20 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized. The in vivo biodistribution and clearance of 11, 12, 16 and 20 were investigated in tumor-bearing mice. Compounds 12 and 16 showed good tumor-selective accumulation among the four derivatives. The time to maximum accumulation of compound 16 in tumor tissue was one-fourth of that of compound 12, and clearance from normal tissues of compound 16 was similar to that of compound 12. The in vivo therapeutic efficacy of PDT using 16, which has twice as many boron atoms as 12, was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 6h after injection of 16. Tumor growth was significantly inhibited by PDT using 16. These results suggested that 16 is a good candidate for both PDT and BNCT of cancer.

  7. Mathematical Model of Bone Remodeling Captures the Antiresorptive and Anabolic Actions of Various Therapies.

    PubMed

    Ross, David S; Mehta, Khamir; Cabal, Antonio

    2017-01-01

    A better understanding of the molecular pathways regulating the bone remodeling process should help in the development of new antiresorptive regulators and anabolic regulators, that is, regulators of bone resorption and of bone formation. Understanding the mechanisms by which parathyroid hormone (PTH) influences bone formation and how it switches from anabolic to catabolic action is important for treating osteoporosis (Poole and Reeve in Curr Opin Pharmacol 5:612-617, 2005). In this paper we describe a mathematical model of bone remodeling that incorporates, extends, and integrates several models of particular aspects of this biochemical system (Cabal et al. in J Bone Miner Res 28(8):1830-1836, 2013; Lemaire et al. in J Theor Biol 229:293-309, 2004; Peterson and Riggs in Bone 46:49-63, 2010; Raposo et al. in J Clin Endocrinol Metab 87(9):4330-4340, 2002; Ross et al. in J Disc Cont Dyn Sys Series B 17(6):2185-2200, 2012). We plan to use this model as a bone homeostasis platform to develop anabolic and antiresorptive compounds. The model will allow us to test hypotheses about the dynamics of compounds and to test the potential benefits of combination therapies. At the core of the model is the idealized account of osteoclast and osteoblast signaling given by Lemaire et al. (J Theor Biol 229:293-309, 2004). We have relaxed some of their assumptions about the roles of osteoprotegerin, transforming growth factor [Formula: see text], and receptor activator of nuclear factor [Formula: see text]B ligand; we have devised more detailed models of the interactions of these species. We have incorporated a model of the effect of calcium sensing receptor antagonists on remodeling (Cabal et al. in J Bone Miner Res 28(8):1830-1836, 2013). We have also incorporated a basic model of the effects of vitamin D on calcium homeostasis. We have included a simple model of the mechanism proposed by Bellido et al. (2003), Ross et al. (J Disc Cont Dyn Sys Series B 17(6):2185-2200, 2012), of the

  8. Field-test results using a nacelle-mounted lidar for improving wind turbine power capture by reducing yaw misalignment

    NASA Astrophysics Data System (ADS)

    Fleming, P. A.; Scholbrock, A. K.; Jehu, A.; Davoust, S.; Osler, E.; Wright, A. D.; Clifton, A.

    2014-06-01

    In this paper, a nacelle-mounted lidar was used to improve the yaw alignment of an experimental wind turbine. Using lidar-recorded data during normal operation, an error correction value for the nacelle vane wind direction measurement used in the yaw controller was determined. A field test was then conducted in which the turbine was operated with and without the correction applied to the yaw controller. Results demonstrated a significant increase in power capture. In addition, the study includes analysis on the impacts on loading of applying this yaw correction. The study demonstrates a successful application in field testing of using a nacelle-mounted lidar to improve turbine performance.

  9. Trivalent galactosyl-functionalized mesoporous silica nanoparticles as a target-specific delivery system for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Lai, Chian-Hui; Lai, Nien-Chu; Chuang, Yung-Jen; Chou, Fong-In; Yang, Chia-Min; Lin, Chun-Cheng

    2013-09-01

    A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium borocaptate (BSH), T-Gal-B-Cy3@MSN provides a higher delivery efficiency (over 40-50 fold) of boron atoms and a better effect of BNCT in neutron irradiation experiments. MTT assays show a very low cytotoxicity for T-Gal-B-Cy3@MSN over a 2 h incubation time. The results are promising for the design of multifunctional MSNs as potential BNCT agents for clinical use.A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium

  10. Field testing of commercially manufactured capture collars on white-tailed deer

    USGS Publications Warehouse

    Mech, L.D.; Kunkel, K.E.; Chapman, R.C.; Kreeger, T.J.

    1990-01-01

    We conducted 31 tests of commercially manufactured capture collars on female white-tailed deer (Odocoileus virginianus) in the Superior National Forest, Minnesota, under temperatures from -37C to 22C. Deer were recaptured in 28 of the 31 tests; in the 3 failures, we remotely released the collars from the deer. Communication with the collars was achieved from up to 3.0 km on the ground and 26.5 km from the air.

  11. Final Report for the “WSU Neutron Capture Therapy Facility Support”

    SciTech Connect

    Gerald E. Tripard; Keith G. Fox

    2006-08-24

    The objective for the cooperative research program for which this report has been written was to provide separate NCT facility user support for the students, faculty and scientists who would be doing the U.S. Department of Energy Office (DOE) of Science supported advanced radiotargeted research at the WSU 1 megawatt TRIGA reactor. The participants were the Idaho National laboratory (INL, P.I., Dave Nigg), the Veterinary Medical Research Center of Washington State University (WSU, Janean Fidel and Patrick Gavin), and the Washington State University Nuclear Radiation Center (WSU, P.I., Gerald Tripard). A significant number of DOE supported modifications were made to the WSU reactor in order to create an epithermal neutron beam while at the same time maintaining the other activities of the 1 MW reactor. These modifications were: (1) Removal of the old thermal column. (2) Construction and insertion of a new epithermal filter, collimator and shield. (3) Construction of a shielded room that could accommodate the very high radiation field created by an intense neutron beam. (4) Removal of the previous reactor core fuel cluster arrangement. (5) Design and loading of the new reactor core fuel cluster arrangement in order to optimize the neutron flux entering the epithermal neutron filter. (6) The integration of the shielded rooms interlocks and radiological controls into the SCRAM chain and operating electronics of the reactor. (7) Construction of a motorized mechanism for moving and remotely controlling the position of the entire reactor bridge. (8) The integration of the reactor bridge control electronics into the SCRAM chain and operating electronics of the reactor. (9) The design, construction and attachment to the support structure of the reactor of an irradiation box that could be inserted into position next to the face of the reactor. (Necessitated by the previously mentioned core rearrangement). All of the above modifications were successfully completed and tested

  12. Gene therapy for muscular dystrophy: moving the field forward.

    PubMed

    Al-Zaidy, Samiah; Rodino-Klapac, Louise; Mendell, Jerry R

    2014-11-01

    Gene therapy for the muscular dystrophies has evolved as a promising treatment for this progressive group of disorders. Although corticosteroids and/or supportive treatments remain the standard of care for Duchenne muscular dystrophy, loss of ambulation, respiratory failure, and compromised cardiac function is the inevitable outcome. Recent developments in genetically mediated therapies have allowed for personalized treatments that strategically target individual muscular dystrophy subtypes based on disease pathomechanism and phenotype. In this review, we highlight the therapeutic progress with emphasis on evolving preclinical data and our own experience in completed clinical trials and others currently underway. We also discuss the lessons we have learned along the way and the strategies developed to overcome limitations and obstacles in this field.

  13. The Perspectives of the Boron Neutron Capture Therapy-Clinical Applications Research and Development in Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Badhrees, I.; Alrumayan, F.; Mahube, F.

    Boron Neutron Capture Therapy (BNCT) is a binary form of experimental radiotherapy which is based on the administration of a drug able to concentrate the isotopes in a tumor cell that later are irradiated with a neutron beam. Even though the first evidence of the success of this treatment dates back many years ago, BNCT showed successful treatment results in malignant melanoma, and Glioblastoma. In order for BNCT to be successful, a sufficient amount of Boron (10B) must be selectively delivered to the tumor cell, and then irradiated by neutrons of sufficient enough. The CS-30 cyclotron at King Faisal Specialist Hospital & Research Center is a positive-ion machine capable of accelerating protons at 26MeV, and other isotopes as well. Although the peak beam intensity from the CS-30 is low, the key to success of using it for the BNCT is by using a high average beam current at low energy. This work is aimed at testing the capability of the CS-30 Cyclotron to produce a low-energy neutron beam to be used to activate the Boron atoms injected into the tumor cell, through simulation of a compatible moderator. We are also planning to measure the overall dosimetry of the energy dose as well as that for the boron in the tumor cell.

  14. In-phantom two-dimensional thermal neutron distribution for intraoperative boron neutron capture therapy of brain tumours

    NASA Astrophysics Data System (ADS)

    Yamamoto, T.; Matsumura, A.; Yamamoto, K.; Kumada, H.; Shibata, Y.; Nose, T.

    2002-07-01

    The aim of this study was to determine the in-phantom thermal neutron distribution derived from neutron beams for intraoperative boron neutron capture therapy (IOBNCT). Gold activation wires arranged in a cylindrical water phantom with (void-in-phantom) or without (standard phantom) a cylinder styrene form placed inside were irradiated by using the epithermal beam (ENB) and the mixed thermal-epithermal beam (TNB-1) at the Japan Research Reactor No 4. With ENB, we observed a flattened distribution of thermal neutron flux and a significantly enhanced thermal flux delivery at a depth compared with the results of using TNB-1. The thermal neutron distribution derived from both the ENB and TNB-1 was significantly improved in the void-in-phantom, and a double high dose area was formed lateral to the void. The flattened distribution in the circumference of the void was observed with the combination of ENB and the void-in-phantom. The measurement data suggest that the ENB may provide a clinical advantage in the form of an enhanced and flattened dose delivery to the marginal tissue of a post-operative cavity in which a residual and/or microscopically infiltrating tumour often occurs. The combination of the epithermal neutron beam and IOBNCT will improve the clinical results of BNCT for brain tumours.

  15. In vitro and in vivo studies of boron neutron capture therapy: boron uptake/washout and cell death.

    PubMed

    Ferrari, C; Bakeine, J; Ballarini, F; Boninella, A; Bortolussi, S; Bruschi, P; Cansolino, L; Clerici, A M; Coppola, A; Di Liberto, R; Dionigi, P; Protti, N; Stella, S; Zonta, A; Zonta, C; Altieri, S

    2011-04-01

    Boron neutron capture therapy (BNCT) is a binary radiotherapy based on thermal-neutron irradiation of cells enriched with (10)B, which produces α particles and (7)Li ions of short range and high biological effectiveness. The selective uptake of boron by tumor cells is a crucial issue for BNCT, and studies of boron uptake and washout associated with cell survival studies can be of great help in developing clinical applications. In this work, boron uptake and washout were characterized both in vitro for the DHDK12TRb (DHD) rat colon carcinoma cell line and in vivo using rats bearing liver metastases from DHD cells. Despite a remarkable uptake, a large boron release was observed after removal of the boron-enriched medium from in vitro cell cultures. However, analysis of boron washout after rat liver perfusion in vivo did not show a significant boron release, suggesting that organ perfusion does not limit the therapeutic effectiveness of the treatment. The survival of boron-loaded cells exposed to thermal neutrons was also assessed; the results indicated that the removal of extracellular boron does not limit treatment effectiveness if adequate amounts of boron are delivered and if the cells are kept at low temperature. Cell survival was also investigated theoretically using a mechanistic model/Monte Carlo code originally developed for radiation-induced chromosome aberrations and extended here to cell death; good agreement between simulation outcomes and experimental data was obtained.

  16. Synthesis and evaluation of thymidine kinase 1-targeting carboranyl pyrimidine nucleoside analogs for boron neutron capture therapy of cancer.

    PubMed

    Agarwal, Hitesh K; Khalil, Ahmed; Ishita, Keisuke; Yang, Weilian; Nakkula, Robin J; Wu, Lai-Chu; Ali, Tehane; Tiwari, Rohit; Byun, Youngjoo; Barth, Rolf F; Tjarks, Werner

    2015-07-15

    A library of sixteen 2nd generation amino- and amido-substituted carboranyl pyrimidine nucleoside analogs, designed as substrates and inhibitors of thymidine kinase 1 (TK1) for potential use in boron neutron capture therapy (BNCT) of cancer, was synthesized and evaluated in enzyme kinetic-, enzyme inhibition-, metabolomic-, and biodistribution studies. One of these 2nd generation carboranyl pyrimidine nucleoside analogs (YB18A [3]), having an amino group directly attached to a meta-carborane cage tethered via ethylene spacer to the 3-position of thymidine, was approximately 3-4 times superior as a substrate and inhibitor of hTK1 than N5-2OH (2), a 1st generation carboranyl pyrimidine nucleoside analog. Both 2 and 3 appeared to be 5'-monophosphorylated in TK1(+) RG2 cells, both in vitro and in vivo. Biodistribution studies in rats bearing intracerebral RG2 glioma resulted in selective tumor uptake of 3 with an intratumoral concentration that was approximately 4 times higher than that of 2. The obtained results significantly advance the understanding of the binding interactions between TK1 and carboranyl pyrimidine nucleoside analogs and will profoundly impact future design strategies for these agents.

  17. Synthesis of a nickel tetracarboranylphenylporphyrin for boron neutron-capture therapy: biodistribution and toxicity in tumor-bearing mice.

    PubMed

    Miura, M; Micca, P L; Fisher, C D; Heinrichs, J C; Donaldson, J A; Finkel, G C; Slatkin, D N

    1996-09-27

    Nickel-2,3,7,8,12,13,17,18-octaacetic acid-5,10,15,20-tetra-[3-carboranyl-methoxyphenyl]-porphyrin octamethylester (NiTCP) was given in a Cremophor EL, a polyethoxylated castor oil, and propylene glycol emulsion to BALB/c mice bearing transplanted s.c. KHJJ mammary carcinomas. A total dose of 244 microg NiTCP/gram body weight (gbw) (54 microg B/gbw) was given in 6 i.p. injections over a 32 hr period. Observations of behavior and changes in body weight and chemical and hematological blood tests indicated little or no toxicity from NiTCP over a period of 6-90 hr after injections. Boron concentrations near tumor margins were 160-180 microg B/g at 41-90 hr after the last injection. Tumor:normal brain boron concentration ratios reached approx. 10:1 and tumor:blood ratios reached approx. 250:1 after 4 days. There was no evidence of thrombocytopenia or other potentially important toxicities. Our findings place NiTCP among the leading candidates for pre-clinical experiments aimed toward improvement upon the compounds being tested for boron neutron-capture therapy of glioblastoma multiforme.

  18. Boron-enriched streptavidin potentially useful as a component of boron carriers for neutron capture therapy of cancer.

    PubMed

    Sano, T

    1999-01-01

    A boron-enriched streptavidin has been prepared by chemical conjugation of a boron-rich compound, B(12)H(11)SH(2)(-) (BSH), to a genetically engineered streptavidin variant. The streptavidin variant used has 20 cysteine residues per molecule, derived from a C-terminal cysteine stretch consisting of five cysteine residues per subunit. Because natural streptavidin has no cysteine residues, the reactive sulfhydryl groups of the cysteine stretch serve as unique conjugation sites for sulfhydryl chemistry. BSH was conjugated irreversibly to the sulfhydryl groups of the streptavidin variant via a sulfhydryl-specific homobifunctional chemical cross-linker. Quantitative boron analysis indicates that the resulting streptavidin-BSH conjugate carries approximately 230 boron atoms/molecule. This indicates that the chemical conjugation of BSH to the streptavidin variant was highly specific and efficient because this method should allow the conjugation of a maximum of 240 boron atoms/streptavidin molecule. This boron-enriched streptavidin retained both full biotin-binding ability and tetrameric structure, suggesting that the conjugation of BSH has little, if any, effect on the fundamental properties of streptavidin. This boron-enriched streptavidin should be very useful as a component of targetable boron carriers for neutron capture therapy of cancer. For example, a monoclonal antibody against a tumor-associated antigen can be attached tightly to the boron-enriched streptavidin upon simple biotinylation, and the resulting conjugate could be used to target boron to tumor cells on which the tumor-associated antigen is overexpressed.

  19. Estimation of relative biological effectiveness for boron neutron capture therapy using the PHITS code coupled with a microdosimetric kinetic model.

    PubMed

    Horiguchi, Hironori; Sato, Tatsuhiko; Kumada, Hiroaki; Yamamoto, Tetsuya; Sakae, Takeji

    2015-03-01

    The absorbed doses deposited by boron neutron capture therapy (BNCT) can be categorized into four components: α and (7)Li particles from the (10)B(n, α)(7)Li reaction, 0.54-MeV protons from the (14)N(n, p)(14)C reaction, the recoiled protons from the (1)H(n, n) (1)H reaction, and photons from the neutron beam and (1)H(n, γ)(2)H reaction. For evaluating the irradiation effect in tumors and the surrounding normal tissues in BNCT, it is of great importance to estimate the relative biological effectiveness (RBE) for each dose component in the same framework. We have, therefore, established a new method for estimating the RBE of all BNCT dose components on the basis of the microdosimetric kinetic model. This method employs the probability density of lineal energy, y, in a subcellular structure as the index for expressing RBE, which can be calculated using the microdosimetric function implemented in the particle transport simulation code (PHITS). The accuracy of this method was tested by comparing the calculated RBE values with corresponding measured data in a water phantom irradiated with an epithermal neutron beam. The calculation technique developed in this study will be useful for biological dose estimation in treatment planning for BNCT.

  20. Intracavitary moderator balloon combined with 252Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations

    PubMed Central

    Brandão, S F

    2015-01-01

    Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

  1. In-phantom two-dimensional thermal neutron distribution for intraoperative boron neutron capture therapy of brain tumours.

    PubMed

    Yamamoto, T; Matsumura, A; Yamamoto, K; Kumada, H; Shibata, Y; Nose, T

    2002-07-21

    The aim of this study was to determine the in-phantom thermal neutron distribution derived from neutron beams for intraoperative boron neutron capture therapy (IOBNCT). Gold activation wires arranged in a cylindrical water phantom with (void-in-phantom) or without (standard phantom) a cylinder styrene form placed inside were irradiated by using the epithermal beam (ENB) and the mixed thermal-epithermal beam (TNB-1) at the Japan Research Reactor No 4. With ENB, we observed a flattened distribution of thermal neutron flux and a significantly enhanced thermal flux delivery at a depth compared with the results of using TNB-1. The thermal neutron distribution derived from both the ENB and TNB-1 was significantly improved in the void-in-phantom, and a double high dose area was formed lateral to the void. The flattened distribution in the circumference of the void was observed with the combination of ENB and the void-in-phantom. The measurement data suggest that the ENB may provide a clinical advantage in the form of an enhanced and flattened dose delivery to the marginal tissue of a post-operative cavity in which a residual and/or microscopically infiltrating tumour often occurs. The combination of the epithermal neutron beam and IOBNCT will improve the clinical results of BNCT for brain tumours.

  2. Estimation of relative biological effectiveness for boron neutron capture therapy using the PHITS code coupled with a microdosimetric kinetic model

    PubMed Central

    Horiguchi, Hironori; Sato, Tatsuhiko; Kumada, Hiroaki; Yamamoto, Tetsuya; Sakae, Takeji

    2015-01-01

    The absorbed doses deposited by boron neutron capture therapy (BNCT) can be categorized into four components: α and 7Li particles from the 10B(n, α)7Li reaction, 0.54-MeV protons from the 14N(n, p)14C reaction, the recoiled protons from the 1H(n, n) 1H reaction, and photons from the neutron beam and 1H(n, γ)2H reaction. For evaluating the irradiation effect in tumors and the surrounding normal tissues in BNCT, it is of great importance to estimate the relative biological effectiveness (RBE) for each dose component in the same framework. We have, therefore, established a new method for estimating the RBE of all BNCT dose components on the basis of the microdosimetric kinetic model. This method employs the probability density of lineal energy, y, in a subcellular structure as the index for expressing RBE, which can be calculated using the microdosimetric function implemented in the particle transport simulation code (PHITS). The accuracy of this method was tested by comparing the calculated RBE values with corresponding measured data in a water phantom irradiated with an epithermal neutron beam. The calculation technique developed in this study will be useful for biological dose estimation in treatment planning for BNCT. PMID:25428243

  3. Synthesis and evaluation of thymidine kinase 1-targeting carboranyl pyrimidine nucleoside analogues for boron neutron capture therapy of cancer

    PubMed Central

    Agarwal, Hitesh K.; Khalil, Ahmed; Ishita, Keisuke; Yang, Weilian; Nakkula, Robin J.; Wu, Lai-Chu; Ali, Tehane; Tiwari, Rohit; Byun, Youngjoo; Barth, Rolf F.; Tjarks, Werner

    2015-01-01

    A library of sixteen 2nd generation amino- and amido-substituted carboranyl pyrimidine nucleoside analogues, designed as substrates and inhibitors of thymidine kinase 1 (TK1) for potential use in boron neutron capture therapy (BNCT) of cancer, was synthesized and evaluated in enzyme kinetic-, enzyme inhibition-, metabolomic-, and biodistribution studies. One of these 2nd generation carboranyl pyrimidine nucleoside analogues (YB18A [3]), having an amino group directly attached to a meta-carborane cage tethered via ethylene spacer to the 3-position of thymidine, was approximately 3–4 times superior as a substrate and inhibitor of hTK1 than N5-2OH (2), a 1st generation carboranyl pyrimidine nucleoside analogue. Both 2 and 3 appeared to be 5′-monophosphorylated in TK1(+) RG2 cells, both in vitro and in vivo. Biodistribution studies in rats bearing intracerebral RG2 glioma resulted in selective tumor uptake of 3 with an intratumoral concentration that was approximately 4 times higher than that of 2. The obtained results significantly advance the understanding of the binding interactions between TK1 and carboranyl pyrimidine nucleoside analogues and will profoundly impact future design strategies for these agents. PMID:26087030

  4. Advantage and limitations of weighting factors and weighted dose quantities and their units in boron neutron capture therapy.

    PubMed

    Rassow, J; Sauerwein, W; Wittig, A; Bourhis-Martin, E; Hideghéty, K; Moss, R

    2004-05-01

    Defining the parameters influencing the biological reaction due to absorbed dose is a continuous topic of research. The main goal of radiobiological research is to translate the measurable dose of ionizing radiation to a quantitative expression of biological effect. Mathematical models based on different biological approaches (e.g., skin reaction, cell culture) provide some estimations that are often misleading and, to some extent, dangerous. Conventional radiotherapy is the simplest case because the primary radiation and secondary radiation are both low linear energy transfer (LET) radiation and have about the same relative biological effectiveness (RBE). Nevertheless, for this one-dose-component case, the dose-effect curves are not linear. In fact, the total absorbed dose and the absorbed dose per fraction as well as the time schedule of the fractionation scheme influence the biological effects. Mathematical models such as the linear-quadratic model can only approximate biological effects. With regard to biological effects, fast neutron therapy is more complex than conventional radiotherapy. Fast neutron beams are always contaminated by gamma rays. As a consequence, biological effects are due to two components, a high-LET component (neutrons) and a low-LET component (photons). A straight transfer of knowledge from conventional radiotherapy to fast neutron therapy is, therefore, not possible: RBE depends on the delivered dose and several other parameters. For dose reporting, the European protocol for fast neutron dosimetry recommends that the total absorbed dose with gamma-ray absorbed dose in brackets is stated. However, boron neutron capture therapy (BNCT) is an even more complex case, because the total absorbed dose is due to four dose components with different LET and RBE. In addition, the terminology and units used by the different BNCT groups is confusing: absorbed dose and weighted dose are both to be stated in grays and are never "photon equivalent." The

  5. Molecular Simulation of Carbon Dioxide Capture by Montmorillonite Using an Accurate and Flexible Force Field

    SciTech Connect

    Romanov, V N; Cygan, R T; Myshakin, E M

    2012-06-21

    Naturally occurring clay minerals provide a distinctive material for carbon capture and carbon dioxide sequestration. Swelling clay minerals, such as the smectite variety, possess an aluminosilicate structure that is controlled by low-charge layers that readily expand to accommodate water molecules and, potentially, CO2. Recent experimental studies have demonstrated the efficacy of intercalating CO2 in the interlayer of layered clays, but little is known about the molecular mechanisms of the process and the extent of carbon capture as a function of clay charge and structure. A series of molecular dynamics simulations and vibrational analyses have been completed to assess the molecular interactions associated with incorporation of CO2 and H2O in the interlayer of montmorillonite clay and to help validate the models with experimental observation. An accurate and fully flexible set of interatomic potentials for CO2 is developed and combined with Clayff potentials to help evaluate the intercalation mechanism and examine the effect of molecular flexibility onthe diffusion rate of CO2 in water.

  6. Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer

    PubMed Central

    2012-01-01

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, the United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na2B12H11SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized

  7. Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer.

    PubMed

    Barth, Rolf F; Vicente, M Graca H; Harling, Otto K; Kiger, W S; Riley, Kent J; Binns, Peter J; Wagner, Franz M; Suzuki, Minoru; Aihara, Teruhito; Kato, Itsuro; Kawabata, Shinji

    2012-08-29

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or "BPA", and sodium borocaptate or "BSH" (Na2B12H11SH). In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger, possibly randomized clinical trials

  8. Impacts on the Hubble Space Telescope Wide Field and Planetary Camera 2: Experimental Simulation of Micrometeoroid Capture

    NASA Technical Reports Server (NTRS)

    Price, M. C.; Kearsley, A. T.; Wozniakiewicz, P. J.; Spratt, J.; Burchell, M. J.; Cole, M. J.; Anz-Meador, P.; Liou, J. C.; Ross, D. K.; Opiela, J.; Grime, G. W.; Webb, R. P.; Jeynes, C.; Palitsin. V. V.; Colaux, J. L.; Griffin, T.; Gerlach, L.

    2014-01-01

    Hypervelocity impact features have been recognized on painted surfaces returned from the Hubble Space Telescope (HST). Here we describe experiments that help us to understand their creation, and the preservation of micrometeoroid (MM) remnants. We simulated capture of silicate and sulfide minerals on the Zinc orthotitanate (ZOT) paint and Al alloy plate of the Wide Field and Planetary Camera 2 (WFPC2) radiator, which was returned from HST after 16 years in low Earth orbit (LEO). Our results also allow us to validate analytical methods for identification of MM (and orbital debris) impacts in LEO.

  9. Boron neutron capture therapy applied to advanced breast cancers: Engineering simulation and feasibility study of the radiation treatment protocol

    NASA Astrophysics Data System (ADS)

    Sztejnberg Goncalves-Carralves, Manuel Leonardo

    This dissertation describes a novel Boron Neutron Capture Therapy (BNCT) application for the treatment of human epidermal growth factor receptor type 2 positive (HER2+) breast cancers. The original contribution of the dissertation is the development of the engineering simulation and the feasibility study of the radiation treatment protocol for this novel combination of BNCT and HER2+ breast cancer treatment. This new concept of BNCT, representing a radiation binary targeted treatment, consists of the combination of two approaches never used in a synergism before. This combination may offer realistic hope for relapsed and/or metastasized breast cancers. This treatment assumes that the boronated anti-HER2 monoclonal antibodies (MABs) are administrated to the patient and accumulate preferentially in the tumor. Then the tumor is destroyed when is exposed to neutron irradiation. Since the use of anti-HER2 MABs yields good and promising results, the proposed concept is expected to amplify the known effect and be considered as a possible additional treatment approach to the most severe breast cancers for patients with metastasized cancer for which the current protocol is not successful and for patients refusing to have the standard treatment protocol. This dissertation makes an original contribution with an integral numerical approach and proves feasible the combination of the aforementioned therapy and disease. With these goals, the dissertation describes the theoretical analysis of the proposed concept providing an integral engineering simulation study of the treatment protocol. An extensive analysis of the potential limitations, capabilities and optimization factors are well studied using simplified models, models based on real CT patients' images, cellular models, and Monte Carlo (MCNP5/X) transport codes. One of the outcomes of the integral dosimetry assessment originally developed for the proposed treatment of advanced breast cancers is the implementation of BNCT

  10. Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

    PubMed Central

    Kueffer, Peter J.; Maitz, Charles A.; Khan, Aslam A.; Schuster, Seth A.; Shlyakhtina, Natalia I.; Jalisatgi, Satish S.; Brockman, John D.; Nigg, David W.; Hawthorne, M. Frederick

    2013-01-01

    The application of boron neutron capture therapy (BNCT) following liposomal delivery of a 10B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2′-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 µg/g tumor at 54 h—with tumor/blood boron ratios being greatest at 96 h (5.68:1; 43 µg boron/g tumor)—following the initial injection. For BNCT experiments, tumor-bearing mice were irradiated 54 h after the initial injection for 30 min with thermal neutrons, resulting in a total fluence of 1.6 × 1012 neutrons per cm2 (±7%). Significant suppression of tumor growth was observed in mice given BNCT vs. control mice (only 424% increase in tumor volume at 14 d post irradiation vs. 1551% in untreated controls). In a separate experiment in which mice were given a second injection/irradiation treatment 7 d after the first, the tumor growth was vastly diminished (186% tumor volume increase at 14 d). A similar response was obtained for mice irradiated for 60 min (169% increase at 14 d), suggesting that neutron fluence was the limiting factor controlling BNCT efficacy in this study. PMID:23536304

  11. Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2.

    PubMed

    Wongthai, Printip; Hagiwara, Kohei; Miyoshi, Yurika; Wiriyasermkul, Pattama; Wei, Ling; Ohgaki, Ryuichi; Kato, Itsuro; Hamase, Kenji; Nagamori, Shushi; Kanai, Yoshikatsu

    2015-03-01

    The efficacy of boron neutron capture therapy relies on the selective delivery of boron carriers to malignant cells. p-Boronophenylalanine (BPA), a boron delivery agent, has been proposed to be localized to cells through transporter-mediated mechanisms. In this study, we screened aromatic amino acid transporters to identify BPA transporters. Human aromatic amino acid transporters were functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic parameters. The roles of the transporters in BPA uptake were characterized in cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used throughout the study. Among aromatic amino acid transporters, ATB(0,+), LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively. Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB(0,+) became significant at 1000 μM, accounting for 20-25% of the total BPA uptake in MCF-7 breast cancer cells. ATB(0,+), LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo. The high and low affinities of LAT1 and ATB(0,+), respectively, differentiate their roles in BPA uptake. ATB(0,+), as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose.

  12. Optimization study for an epithermal neutron beam for boron neutron capture therapy at the University of Virginia Research Reactor

    SciTech Connect

    Burns, Jr., Thomas Dean

    1995-05-01

    The non-surgical brain cancer treatment modality, Boron Neutron Capture Therapy (BNCT), requires the use of an epithermal neutron beam. This purpose of this thesis was to design an epithermal neutron beam at the University of Virginia Research Reactor (UVAR) suitable for BNCT applications. A suitable epithermal neutron beam for BNCT must have minimal fast neutron and gamma radiation contamination, and yet retain an appreciable intensity. The low power of the UVAR core makes reaching a balance between beam quality and intensity a very challenging design endeavor. The MCNP monte carlo neutron transport code was used to develop an equivalent core radiation source, and to perform the subsequent neutron transport calculations necessary for beam model analysis and development. The code accuracy was validated by benchmarking output against experimental criticality measurements. An epithermal beam was designed for the UVAR, with performance characteristics comparable to beams at facilities with cores of higher power. The epithermal neutron intensity of this beam is 2.2 x 108 n/cm2 • s. The fast neutron and gamma radiation KERMA factors are 10 x 10-11cGy•cm2/nepi and 20 x 10-11 cGy•cm2/nepi , respectively, and the current-to-flux ratio is 0.85. This thesis has shown that the UVAR has the capability to provide BNCT treatments, however the performance characteristics of the final beam of this study were limited by the low core power.

  13. Feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma from a viewpoint of dose distribution analysis

    SciTech Connect

    Suzuki, Minoru . E-mail: msuzuki@rri.kyoto-u.ac.jp; Sakurai, Yoshinori; Masunaga, Shinichiro; Kinashi, Yuko; Nagata, Kenji; Maruhashi, Akira; Ono, Koji

    2006-12-01

    Purpose: To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. Methods and Materials: The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The {sup 1}B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumors and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D{sub 05} and D{sub 95}, were adopted as the representative dose for the maximum and minimum dose, respectively. Results: When the D{sub 05} to the normal ipsilateral lung was 5 Gy-Eq, the D{sub 95} and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D{sub 05} and D{sub 95} doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. Conclusions: From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses.

  14. Boron neutron capture therapy of the rat 9L gliosarcoma: evaluation of the effects of shark cartilage.

    PubMed

    Morris, G M; Coderre, J A; Micca, P L; Lombardo, D T; Hopewell, J W

    2000-04-01

    A number of anti-angiogenic substances are now under evaluation, both experimentally and clinically, as potential agents for the treatment of cancer. It has recently been demonstrated that anti-angiogenic agents can increase the therapeutic potential of photon irradiation in a range of tumour models. In the present communication a preliminary assessment is made of the effects of shark cartilage on the response of the rat 9L gliosarcoma to boron neutron capture therapy (BNCT). Shark cartilage was administered orally as an aqueous suspension at a daily dose of approximately 2000 mg kg-1 body weight. The mean survival time of rats receiving no treatment was 20.7 +/- 0.5 days post intracranial tumour implantation. Administration of shark cartilage alone extended the survival time. Two of the rats treated with shark cartilage were healthy and fully active at the end of the evaluation period (43 days post implantation). At autopsy the brain tumours of these animals were a factor of approximately 4 smaller than controls. In a repeat study with shark cartilage alone the survival time was extended by approximately 30%. After boronophenylalanine-mediated BNCT, with or without shark cartilage, the survival time of rats that eventually became moribund was increased by a factor of approximately 2 relative to controls. In both treatment groups approximately 20% of rats were healthy at 1 year after BNCT. There was no evidence of residual tumour at post-mortem. It was concluded that shark cartilage, when given alone, significantly increased the survival time of tumour-bearing rats, presumably owing to an anti-angiogenic effect. However, the survival data suggested that boronophenylalanine-mediated BNCT did not appear to be enhanced by the administration of shark cartilage.

  15. Boron neutron capture therapy (BNCT) for the treatment of liver metastases: biodistribution studies of boron compounds in an experimental model.

    PubMed

    Garabalino, Marcela A; Monti Hughes, Andrea; Molinari, Ana J; Heber, Elisa M; Pozzi, Emiliano C C; Cardoso, Jorge E; Colombo, Lucas L; Nievas, Susana; Nigg, David W; Aromando, Romina F; Itoiz, Maria E; Trivillin, Verónica A; Schwint, Amanda E

    2011-03-01

    We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of (10)B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na(2)(10)B(10)H(10)), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.

  16. Biodistribution of boron compounds in an animal model of human undifferentiated thyroid cancer for boron neutron capture therapy.

    PubMed

    Dagrosa, M Alejandra; Viaggi, Mabel; Rebagliati, Raul Jimenez; Batistoni, Daniel; Kahl, Stephen B; Juvenal, Guillermo J; Pisarev, Mario A

    2005-01-01

    Undifferentiated thyroid carcinoma (UTC) is a rapidly growing, highly invasive malignant tumor that currently lacks any effective treatment. Boron neutron capture therapy (BNCT) has been investigated recently for some types of tumors including glioblastoma multiforme and malignant melanoma. In previous studies we have shown the selective uptake of p-boronophenylalanine (BPA) by undifferentiated thyroid cancer cells in vitro and in vivo, as well as the histologic cure of 50% of the nude mice transplanted with human UTC cells when treated with BPA and an appropriate neutron beam. The present studies were performed to further optimize this treatment through the investigation of a boronated porphyrin, both alone and in combination with BPA. In vitro studies with cells in culture showed that BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(alpha,beta-dihydroxyethyl)-deutero-porphyrin IX) is localized intracellularly, with a highest concentration in the 11500g (mitochondrial-enriched pellet) fraction. When BOPP was administered alone to NIH nude mice transplanted with UTC human cells, no significant tumor uptake or selectivity in our in vivo model was observed. In contrast, when BOPP was injected 5-7 days before BPA and the animals were sacrificed 60 min after administration of BPA, a significant increase in boron uptake by the tumor was found (38-45 ppm with both compounds vs 20 ppm with BPA alone). On day 5 the tissue boron selectivity ratios were tumor/blood approximately 3.8 and tumor/distal skin approximately 1.8. Other important ratios were tumor/thyroid approximately 6.6 and tumor/lung approximately 2.9. These results open the possibility of improving the efficacy of BNCT for the treatment of this so far "orphan" tumor.

  17. Pharmacokinetics of core-polymerized, boron-conjugated micelles designed for boron neutron capture therapy for cancer.

    PubMed

    Sumitani, Shogo; Oishi, Motoi; Yaguchi, Tatsuya; Murotani, Hiroki; Horiguchi, Yukichi; Suzuki, Minoru; Ono, Koji; Yanagie, Hironobu; Nagasaki, Yukio

    2012-05-01

    Core-polymerized and boron-conjugated micelles (PM micelles) were prepared by free radical copolymerization of a PEG-b-PLA block copolymer bearing an acetal group and a methacryloyl group (acetal-PEG-b-PLA-MA), with 1-(4-vinylbenzyl)-closo-carborane (VB-carborane), and the utility of these micelles as a tumor-targeted boron delivery system was investigated for boron neutron capture therapy (BNCT). Non-polymerized micelles (NPM micelles) that incorporated VB-carborane physically showed significant leakage of VB-carborane (ca. 50%) after 12 h incubation with 10% fetal bovine serum (FBS) at 37 °C. On the other hand, no leakage from the PM micelles was observed even after 48 h of incubation. To clarify the pharmacokinetics of the micelles, (125)I (radioisotope)-labeled PM and NPM micelles were administered to colon-26 tumor-bearing BALB/c mice. The (125)I-labeled PM micelles showed prolonged blood circulation (area under the concentration curve (AUC): 943.4) than the (125)I-labeled NPM micelles (AUC: 495.1), whereas tumor accumulation was similar for both types of micelles (AUC(PM micelle): 249.6, AUC(NPM micelle): 201.1). In contrast, the tumor accumulation of boron species in the PM micelles (AUC: 268.6) was 7-fold higher than the NPM micelles (AUC: 37.1), determined by ICP-AES. Thermal neutron irradiation yielded tumor growth suppression in the tumor-bearing mice treated with the PM micelles without reduction in body weight. On the basis of these data, the PM micelles represent a promising approach to the creation of boron carrier for BNCT.

  18. Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

    SciTech Connect

    Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari; Elisa M. Heber; Emiliano C. C. Pozzi; Maria E. Itoiz; Veronica A. Trivillin; Amanda E. Schwint; Jorge E. Cardoso; Lucas L. Colombo; Susana Nievas; David W. Nigg; Romina F. Aromando

    2011-03-01

    Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.

  19. Synthesis of copper octabromotetracarboranylphenylporphyrin for boron neutron capture therapy and its toxicity and biodistribution in tumour-bearing mice.

    PubMed

    Miura, M; Morris, G M; Micca, P L; Nawrocky, M M; Makar, M S; Cook, S P; Slatkin, D N

    2004-07-01

    Copper tetracarboranyltetraphenylporphyrin (CuTCPH) is a minimally toxic carborane-containing porphyrin that has safely delivered high concentrations of boron for experimental boron neutron capture therapy (BNCT). Copper octabromotetracarboranylphenylporphyrin (CuTCPBr), synthesized by bromination of CuTCPH, is one of several new minimally toxic analogues of CuTCPH being studied in our laboratory, which could possess comparable or better tumour-targeting properties with enhanced tumour cytotoxicity. Its biodistribution, biokinetics and toxicity in mice with subcutaneous EMT-6 (mammary) or SCCVII (squamous cell) carcinomas were compared with those of CuTCPH. The administration of approximately 200 mg kg(-1) of either porphyrin in six intraperitoneal injections over 2 days had no apparent effect, but administration of approximately 400 mg kg(-1) slightly lowered body weights, elevated alanine and aspartate transaminase activities in blood plasma, and depressed blood platelet counts for several days. Enzymes and platelets returned to normal within 5 days after those injections and body weights returned to normal within 2 weeks. High average concentrations of boron from either porphyrin were achieved in the two tumour models from a total dose of approximately 200 mg kg(-1). The high tumour boron concentration decreased slowly while concentrations in blood decreased rapidly. Boron concentrations in brain and skin were consistently lower than in tumour by a factor of 10 or more. Although either CuTCPH or CuTCPBr can be labelled with (64)Cu for imaging by positron emission tomography (PET), CuTCPBr can also be labelled by (76)Br, another PET-imageable nuclide.

  20. A study on the optimum fast neutron flux for boron neutron capture therapy of deep-seated tumors.

    PubMed

    Rasouli, Fatemeh S; Masoudi, S Farhad

    2015-02-01

    High-energy neutrons, named fast neutrons which have a number of undesirable biological effects on tissue, are a challenging problem in beam designing for Boron Neutron Capture Therapy, BNCT. In spite of this fact, there is not a widely accepted criterion to guide the beam designer to determine the appropriate contribution of fast neutrons in the spectrum. Although a number of researchers have proposed a target value for the ratio of fast neutron flux to epithermal neutron flux, it can be shown that this criterion may not provide the optimum treatment condition. This simulation study deals with the determination of the optimum contribution of fast neutron flux in the beam for BNCT of deep-seated tumors. Since the dose due to these high-energy neutrons damages shallow tissues, delivered dose to skin is considered as a measure for determining the acceptability of the designed beam. To serve this purpose, various beam shaping assemblies that result in different contribution of fast neutron flux are designed. The performances of the neutron beams corresponding to such configurations are assessed in a simulated head phantom. It is shown that the previously used criterion, which suggests a limit value for the contribution of fast neutrons in beam, does not necessarily provide the optimum condition. Accordingly, it is important to specify other complementary limits considering the energy of fast neutrons. By analyzing various neutron spectra, two limits on fast neutron flux are proposed and their validity is investigated. The results show that considering these limits together with the widely accepted IAEA criteria makes it possible to have a more realistic assessment of sufficiency of the designed beam. Satisfying these criteria not only leads to reduction of delivered dose to skin, but also increases the advantage depth in tissue and delivered dose to tumor during the treatment time. The Monte Carlo Code, MCNP-X, is used to perform these simulations.

  1. Demonstration of three-dimensional deterministic radiation transport theory dose distribution analysis for boron neutron capture therapy.

    PubMed

    Nigg, D W; Randolph, P D; Wheeler, F J

    1991-01-01

    The Monte Carlo stochastic simulation technique has traditionally been the only well-recognized method for computing three-dimensional radiation dose distributions in connection with boron neutron capture therapy (BNCT) research. A deterministic approach to this problem would offer some advantages over the Monte Carlo method. This paper describes an application of a deterministic method to analytically simulate BNCT treatment of a canine head phantom using the epithermal neutron beam at the Brookhaven medical research reactor (BMRR). Calculations were performed with the TORT code from Oak Ridge National Laboratory (ORNL), an implementation of the discrete ordinates, or Sn method. Calculations were from first principles and used no empirical correction factors. The phantom surface was modeled by flat facets of approximately 1 cm2. The phantom interior was homogeneous. Energy-dependent neutron and photon scalar fluxes were calculated on a 32 x 16 x 22 mesh structure with 96 discrete directions in angular phase space. The calculation took 670 min on an Apollo DN10000 workstation. The results were subsequently integrated over energy to obtain full three-dimensional dose distributions. Isodose contours and depth-dose curves were plotted for several separate dose components of interest. Phantom measurements were made by measuring neutron activation (and therefore neutron flux) as a function of depth in copper-gold alloy wires that were inserted through catheters placed in holes drilled in the phantom. Measurements agreed with calculations to within about 15%. The calculations took about an order of magnitude longer than comparable Monte Carlo calculations but provided various conveniences, as well as a useful check.

  2. Fluence field modulated CT on a clinical TomoTherapy radiation therapy machine

    NASA Astrophysics Data System (ADS)

    Szczykutowicz, Timothy P.; Hermus, James

    2015-03-01

    Purpose: The multi-leaf collimator (MLC) assembly present on TomoTherapy (Accuray, Madison WI) radiation therapy (RT) and mega voltage CT machines is well suited to perform fluence field modulated CT (FFMCT). In addition, there is a demand in the RT environment for FFMCT imaging techniques, specifically volume of interest (VOI) imaging. Methods: A clinical TomoTherapy machine was programmed to deliver 30% imaging dose outside predefined VOIs. Four different size ROIs were placed at varying distances from isocenter. Projections intersecting the VOI received "full dose" while those not intersecting the VOI received 30% of the dose (i.e. the incident fluence for non VOI projections was 30% of the incident fluence for projections intersecting the VOI). Additional scans without fluence field modulation were acquired at "full" and 30% dose. The noise (pixel standard deviation) was measured inside the VOI region and compared between the three scans. Results: The VOI-FFMCT technique produced an image noise 1.09, 1.05, 1.05, and 1.21 times higher than the "full dose" scan for ROI sizes of 10 cm, 13 cm, 10 cm, and 6 cm respectively within the VOI region. Conclusions: Noise levels can be almost unchanged within clinically relevant VOIs sizes for RT applications while the integral imaging dose to the patient can be decreased, and/or the image quality in RT can be dramatically increased with no change in dose relative to non-FFMCT RT imaging. The ability to shift dose away from regions unimportant for clinical evaluation in order to improve image quality or reduce imaging dose has been demonstrated. This paper demonstrates that FFMCT can be performed using the MLC on a clinical TomoTherapy machine for the first time.

  3. Static Magnetic Field Therapy: A Critical Review of Treatment Parameters

    PubMed Central

    Wahbeh, Helané; Harling, Noelle; Connelly, Erin; Schiffke, Heather C.; Forsten, Cora; Gregory, William L.; Markov, Marko S.; Souder, James J.; Elmer, Patricia; King, Valerie

    2009-01-01

    Static magnetic field (SMF) therapy, applied via a permanent magnet attached to the skin, is used by people worldwide for self-care. Despite a lack of established SMF dosage and treatment regimens, multiple studies are conducted to evaluate SMF therapy effectiveness. Our objectives in conducting this review are to:(i) summarize SMF research conducted in humans; (ii) critically evaluate reporting quality of SMF dosages and treatment parameters and (iii) propose a set of criteria for reporting SMF treatment parameters in future clinical trials. We searched 27 electronic databases and reference lists. Only English language human studies were included. Excluded were studies of electromagnetic fields, transcranial magnetic stimulation, magnets placed on acupuncture points, animal studies, abstracts, posters and editorials. Data were extracted on clinical indication, study design and 10 essential SMF parameters. Three reviewers assessed quality of reporting and calculated a quality assessment score for each of the 10 treatment parameters. Fifty-six studies were reviewed, 42 conducted in patient populations and 14 in healthy volunteers. The SMF treatment parameters most often and most completely described were site of application, magnet support device and frequency and duration of application. Least often and least completely described were characteristics of the SMF: magnet dimensions, measured field strength and estimated distance of the magnet from the target tissue. Thirty-four (61%) of studies failed to provide enough detail about SMF dosage to permit protocol replication by other investigators. Our findings highlight the need to optimize SMF dosing parameters for individual clinical conditions before proceeding to a full-scale clinical trial. PMID:18955243

  4. Sc and neutron-capture abundances in Galactic low- and high-α field halo stars

    NASA Astrophysics Data System (ADS)

    Fishlock, C. K.; Yong, D.; Karakas, A. I.; Alves-Brito, A.; Meléndez, J.; Nissen, P. E.; Kobayashi, C.; Casey, A. R.

    2017-01-01

    We determine relative abundance ratios for the neutron-capture elements Zr, La, Ce, Nd, and Eu for a sample of 27 Galactic dwarf stars with -1.5 < [Fe/H] <-0.8. We also measure the iron-peak element Sc. These stars separate into three populations (low- and high-α halo and thick-disc stars) based on the [α/Fe] abundance ratio and their kinematics as discovered by Nissen & Schuster. We find differences between the low- and high-α groups in the abundance ratios of [Sc/Fe], [Zr/Fe], [La/Zr], [Y/Eu], and [Ba/Eu] when including Y and Ba from Nissen & Schuster. For all ratios except [La/Zr], the low-α stars have a lower abundance compared to the high-α stars. The low-α stars display the same abundance patterns of high [Ba/Y] and low [Y/Eu] as observed in present-day dwarf spheroidal galaxies, although with smaller abundance differences, when compared to the high-α stars. These distinct chemical patterns have been attributed to differences in the star formation rate between the two populations and the contribution of low-metallicity, low-mass asymptotic giant branch (AGB) stars to the low-α population. By comparing the low-α population with AGB stellar models, we place constraints on the mass range of the AGB stars.

  5. Observations of a Newly "Captured" Magnetosheath Field Line: Evidence for "Double Reconnection"

    NASA Technical Reports Server (NTRS)

    Chandler, Michael O.; Avanov, Levon A.; Craven, Paul D.; Mozer, Forrest S.; Moore, Thomas E.

    2007-01-01

    We have begun an investigation of the nature of the low-latitude boundary layer in the mid-altitude cusp region using data from the Polar spacecraft. This region has been routinely sampled for about three months each year for the periods 1999-2001 and 2004-2006. The low-to-mid-energy ion instruments frequently observed dense, magnetosheath-like plasma deep (in terms of distance from the magnetopause and in invariant latitude) in the magnetosphere. One such case, taken during a period of northward interplanetary magnetic field (IMF), shows magnetosheath ions within the magnetosphere with velocity distributions resulting from two separate merging sites along the same field lines. Cold ionospheric ions were also observed counterstreaming along the field lines, evidence that these field lines were closed. These results are consistent with the hypothesis that double merging can produce closed field .lines populated by solar wind plasma. Through the use of individual cases such as this and statistical studies of a broader database we seek to understand the morphology of the LLBL as it projects from the sub-solar region into the cusp. We will present preliminary results of our ongoing study.

  6. Linking canopy reflectance to crop structure and photosynthesis to capture and interpret spatiotemporal dimensions of per-field photosynthetic productivity

    NASA Astrophysics Data System (ADS)

    Xue, Wei; Jeong, Seungtaek; Ko, Jonghan; Tenhunen, John

    2017-03-01

    Nitrogen and water availability alter canopy structure and physiology, and thus crop growth, yielding large impacts on ecosystem-regulating/production provisions. However, to date, explicitly quantifying such impacts remains challenging partially due to lack of adequate methodology to capture spatial dimensions of ecosystem changes associated with nitrogen and water effects. A data fitting, where close-range remote-sensing measurements of vegetation indices derived from a handheld instrument and an unmanned aerial vehicle (UAV) system are linked to in situ leaf and canopy photosynthetic traits, was applied to capture and interpret inter- and intra-field variations in gross primary productivity (GPP) in lowland rice grown under flooded conditions (paddy rice, PD) subject to three nitrogen application rates and under rainfed conditions (RF) in an East Asian monsoon region of South Korea. Spatial variations (SVs) in both GPP and light use efficiency (LUEcabs) early in the growing season were enlarged by nitrogen addition. The nutritional effects narrowed over time. A shift in planting culture from flooded to rainfed conditions strengthened SVs in GPP and LUEcabs. Intervention of prolonged drought late in the growing season dramatically intensified SVs that were supposed to seasonally decrease. Nevertheless, nitrogen addition effects on SV of LUEcabs at the early growth stage made PD fields exert greater SVs than RF fields. SVs of GPP across PD and RF rice fields were likely related to leaf area index (LAI) development less than to LUEcabs, while numerical analysis suggested that considering strength in LUEcabs and its spatial variation for the same crop type tends to be vital for better evaluation in landscape/regional patterns of ecosystem photosynthetic productivity at critical phenology stages.

  7. Synthesis and in vitro evaluation of thiododecaborated α, α- cycloalkylamino acids for the treatment of malignant brain tumors by boron neutron capture therapy.

    PubMed

    Hattori, Yoshihide; Kusaka, Shintaro; Mukumoto, Mari; Ishimura, Miki; Ohta, Yoichiro; Takenaka, Hiroshi; Uehara, Kouki; Asano, Tomoyuki; Suzuki, Minoru; Masunaga, Shin-Ichiro; Ono, Koji; Tanimori, Shinji; Kirihata, Mitsunori

    2014-12-01

    Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11](2-)-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.

  8. Acoustic field of a ballistic shock wave therapy device.

    PubMed

    Cleveland, Robin O; Chitnis, Parag V; McClure, Scott R

    2007-08-01

    Shock wave therapy (SWT) refers to the use of focused shock waves for treatment of musculoskeletal indications including plantar fascitis and dystrophic mineralization of tendons and joint capsules. Measurements were made of a SWT device that uses a ballistic source. The ballistic source consists of a handpiece within which compressed air (1-4 bar) is used to fire a projectile that strikes a metal applicator placed on the skin. The projectile generates stress waves in the applicator that transmit as pressure waves into tissue. The acoustic fields from two applicators were measured: one applicator was 15 mm in diameter and the surface slightly convex and the second was 12 mm in diameter the surface was concave. Measurements were made in a water tank and both applicators generated a similar pressure pulse consisting of a rectangular positive phase (4 micros duration and up to 8 MPa peak pressure) followed by a predominantly negative tail (duration of 20 micros and peak negative pressure of -6 MPa), with many oscillations. The rise times of the waveforms were around 1 micros and were shown to be too long for the pulses to be considered shock waves. Measurements of the field indicated that region of high pressure was restricted to the near-field (20-40 mm) of the source and was consistent with the Rayleigh distance. The measured acoustic field did not display focusing supported by calculations, which demonstrated that the radius of curvature of the concave surface was too large to effect a focusing gain. Other SWT devices use electrohydraulic, electromagnetic and piezoelectric sources that do result in focused shock waves. This difference in the acoustic fields means there is potentially a significant mechanistic difference between a ballistic source and other SWT devices.

  9. Field captures of wild melon fly (Diptera: Tephritidae) with an improved male attractant, raspberry ketone formate.

    PubMed

    Jang, Eric B; Casana-Giner, Victor; Oliver, James E

    2007-08-01

    Field-trapping evaluations of the new male attractant, formic acid 4-(3-oxobutyl) phenyl ester (raspberry ketone formate [RKF]) were conducted in Hawaii with wild populations of melon flies, Bactrocera cucurbitae Coquillett (Diptera: Tephritidae), to determine its activity in the field and to evaluate new plastic matrix formulations. All tests were compared with the standard melon fly attractant 4-(4-acetoxyphenyl) -2-butanone (cuelure [CL]), which is the attractant of choice for detection programs aimed at melon fly and other cuelure-responding Bactrocera fruit flies. Results of these tests over a range of doses on cotton wicks showed that at a 1-g dose raspberry ketone formate was 1.5-2 times more attractive compared with cuelure for up to 11 wk in the field. Lower doses applied on cotton wicks were less active, presumably due to hydrolysis of RKF to raspberry ketone. Raspberry ketone formate embedded in a plastic plug formulation also was field tested, and it was shown to be more attractive to male melon fly compared with cuelure. The use of this new attractant in control and detection programs is discussed.

  10. Phase-stepping interferometric system for capturing instantaneous flow field under harsh environments

    NASA Astrophysics Data System (ADS)

    Burner, Alpheus W.; Yu, Enxi; Cha, Soyoung S.

    2003-04-01

    Interferometric reconstruction of a flow field usually consists of three steps. The first is to record interferograms, the second is to extract phase information from interferograms and the final is for numerical inversion of the phase data. In interferometric flow recording, test section enclosures and opaque models are frequently present, blocking a portion of the probing rays or restricting the view angle of the field to produce a partial data set especially for interferometric tomography. It also involves very harsh environments with external vibrations and disturbances of the ambient air. The ill-posed problem is susceptible to experimental noise and can produce serious distortions in reconstruction. Interferometric reconstruction of flow fields thus needs accurate phase information extraction. The major problem encountered in interferometry is that it is extremely sensitive to external disturbances including the vibration of the optical setup. This is true especially for aerodynamic wind tunnel testing. For successful application of interferometry to experimental fluid mechancis and heat/mass transfer, efficient mechanisms for accurate flow-field recording and information extraction are thus very necessary. In interferometric recording, use of the phase stepping techniques is desirable whenever possible, since they provide the most accuracy. However, they are not applicable under disturbing conditions; that is, under harsh environments. In an effort to provide accurate interferometric data, we device interferogram recording and reduction techniques. They are based on a phase-stepping method: however, applicable to harsh environments including wind tunnel testing. Here we present the governing concepts, investigation results, and application demonstration of our approaches for practical flow measurements. The developed approaches are tested through phoase extraction and 3D reconstruction of an experimental flow field, which is designed for future wind tunnel

  11. First Evaluation of the Biologic Effectiveness Factors of Boron Neutron Capture Therapy (BNCT) in a Human Colon Carcinoma Cell Line

    SciTech Connect

    Dagrosa, Maria Alejandra; Crivello, Martin; Perona, Marina; Thorp, Silvia; Santa Cruz, Gustavo Alberto; Pozzi, Emiliano; Casal, Mariana; Thomasz, Lisa; Cabrini, Romulo; Kahl, Steven; Juvenal, Guillermo Juan; Pisarev, Mario Alberto

    2011-01-01

    Purpose: DNA lesions produced by boron neutron capture therapy (BNCT) and those produced by gamma radiation in a colon carcinoma cell line were analyzed. We have also derived the relative biologic effectiveness factor (RBE) of the neutron beam of the RA-3- Argentine nuclear reactor, and the compound biologic effectiveness (CBE) values for p-boronophenylalanine ({sup 10}BPA) and for 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX ({sup 10}BOPP). Methods and Materials: Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm {sup 10}B) + neutrons, (2) BOPP (10 ppm {sup 10}B) + neutrons, (3) neutrons alone, and (4) gamma rays ({sup 60}Co source at 1 Gy/min dose-rate). Different irradiation times were used to obtain total absorbed doses between 0.3 and 5 Gy ({+-}10%) (thermal neutrons flux = 7.5 10{sup 9} n/cm{sup 2} sec). Results: The frequency of micronucleated binucleated cells and the number of micronuclei per micronucleated binucleated cells showed a dose-dependent increase until approximately 2 Gy. The response to gamma rays was significantly lower than the response to the other treatments (p < 0.05). The irradiations with neutrons alone and neutrons + BOPP showed curves that did not differ significantly from, and showed less DNA damage than, irradiation with neutrons + BPA. A decrease in the surviving fraction measured by 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay as a function of the absorbed dose was observed for all the treatments. The RBE and CBE factors calculated from cytokinesis block micronucleus (CBMN) and MTT assays were, respectively, the following: beam RBE: 4.4 {+-} 1.1 and 2.4 {+-} 0.6; CBE for BOPP: 8.0 {+-} 2.2 and 2.0 {+-} 1; CBE for BPA: 19.6 {+-} 3.7 and 3.5 {+-} 1.3. Conclusions: BNCT and gamma irradiations showed different genotoxic patterns. To our knowledge, these values represent the first experimental ones obtained for the RA-3 in a

  12. Effect of electroporation on cell killing by boron neutron capture therapy using borocaptate sodium (10B-BSH).

    PubMed

    Ono, K; Kinashi, Y; Masunaga, S; Suzuki, M; Takagaki, M

    1998-12-01

    The cell membrane permeability of 10B-enriched borocaptate sodium (BSH) and the extent to which BSH is accumulated in cells are controversial. To elucidate these points and to enhance the accumulation of BSH in cells, the effect of electroporation on boron neutron capture therapy (BNCT) using BSH was investigated. The first group of SCCVII tumor cells was incubated in culture medium with 10B-BSH or 10B-enriched boric acid, and exposed to neutrons from the heavy water facility of the Kyoto University Reactor. More than 99% of neutrons were thermal neutrons at flux base. The second group was pretreated with electroporation in combination with 10B-BSH, and thereafter the cells were irradiated with neutrons. The cell-killing effect of BNCT was measured by colony formation assay. The surviving cell fraction decreased exponentially with neutron fluence, and addition of BSH significantly enhanced the cell-killing effect of NCT depending on 10B concentration and the preincubation time of cells in the BSH-containing culture medium. The electroporation of cells with BSH markedly enhanced the BNCT effect in comparison with that obtained with preincubation alone. The effect of BSH-BNCT with electroporation was almost equal to that of BNCT using 10B-boric acid at the same 10B concentration. The effect of BNCT on cells pretreated with BSH and electroporation was not reduced by repeated washing of the cells before neutron irradiation. Decrease of the effect of BSH-BNCT plus electroporation with increase in the waiting time between the electroporation and the neutron irradiation could be explained in terms of the extent of cell growth during that time. These data suggest that BSH penetrates the cells slowly and remains after washing. Electroporation can introduce BSH into the cells very efficiently, and BSH thus introduced stays in the cells and is not lost in spite of the intensive washing of the cells. Therefore, if electroporation is applied to tumors after BSH injection, 10B

  13. Simultaneous multiview capture and fusion improves spatial resolution in wide-field and light-sheet microscopy

    PubMed Central

    Wu, Yicong; Chandris, Panagiotis; Winter, Peter W.; Kim, Edward Y.; Jaumouillé, Valentin; Kumar, Abhishek; Guo, Min; Leung, Jacqueline M.; Smith, Corey; Rey-Suarez, Ivan; Liu, Huafeng; Waterman, Clare M.; Ramamurthi, Kumaran S.; La Riviere, Patrick J.; Shroff, Hari

    2016-01-01

    Most fluorescence microscopes are inefficient, collecting only a small fraction of the emitted light at any instant. Besides wasting valuable signal, this inefficiency also reduces spatial resolution and causes imaging volumes to exhibit significant resolution anisotropy. We describe microscopic and computational techniques that address these problems by simultaneously capturing and subsequently fusing and deconvolving multiple specimen views. Unlike previous methods that serially capture multiple views, our approach improves spatial resolution without introducing any additional illumination dose or compromising temporal resolution relative to conventional imaging. When applying our methods to single-view wide-field or dual-view light-sheet microscopy, we achieve a twofold improvement in volumetric resolution (~235 nm × 235 nm × 340 nm) as demonstrated on a variety of samples including microtubules in Toxoplasma gondii, SpoVM in sporulating Bacillus subtilis, and multiple protein distributions and organelles in eukaryotic cells. In every case, spatial resolution is improved with no drawback by harnessing previously unused fluorescence. PMID:27761486

  14. Scanning behavior by larvae of the predacious diving beetle, Thermonectus marmoratus (Coleoptera: Dytiscidae) enlarges visual field prior to prey capture.

    PubMed

    Buschbeck, Elke K; Sbita, Sarah J; Morgan, Randy C

    2007-09-01

    Larvae of the predaceous diving beetle Thermonectus marmoratus bear six stemmata on each side of their head, two of which form relatively long tubes with linear retinas at their proximal ends. The physical organization of these eyes results in extremely narrow visual fields that extend only laterally in the horizontal body plane. There are other examples of animals possessing eyes with predominantly linear retinas, or with linear arrangements of specific receptor types. In these animals, the eyes, or parts of the eyes, are movable and perform scanning movements to increase the visual field. Based on anatomical data and observations of relatively transparent, immobilized young larvae, we report here that T. marmoratus larvae are incapable of moving their eyes or any part of their eyes within the head capsule. However, they do perform a series of bodily dorso-ventral pivots prior to prey capture, behaviorally extending the vertical visual field from 2 degrees to up to 50 degrees. Frame-by-frame analysis shows that such behavior is performed within a characteristic distance to the prey. These data provide first insights into the function of the very peculiar anatomical eye organization of T. marmoratus larvae.

  15. Full Scale Field Trial of the Low Temperature Mercury Capture Process

    SciTech Connect

    Locke, James; Winschel, Richard

    2012-05-21

    CONSOL Energy Inc., with partial funding from the Department of Energy (DOE) National Energy Technology Laboratory, designed a full-scale installation for a field trial of the Low-Temperature Mercury Control (LTMC) process, which has the ability to reduce mercury emissions from coal-fired power plants by over 90 percent, by cooling flue gas temperatures to approximately 230°F and absorbing the mercury on the native carbon in the fly ash, as was recently demonstrated by CONSOL R&D on a slip-stream pilot plant at the Allegheny Energy Mitchell Station with partial support by DOE. LTMC has the potential to remove over 90 percent of the flue gas mercury at a cost at least an order of magnitude lower (on a $/lb mercury removed basis) than activated carbon injection. The technology is suitable for retrofitting to existing and new plants, and, although it is best suited to bituminous coal-fired plants, it may have some applicability to the full range of coal types. Installation plans were altered and moved from the original project host site, PPL Martins Creek plant, to a second host site at Allegheny Energy's R. Paul Smith plant, before installation actually occurred at the Jamestown (New York) Board of Public Utilities (BPU) Samuel A. Carlson (Carlson) Municipal Generating Station Unit 12, where the LTMC system was operated on a limited basis. At Carlson, over 60% mercury removal was demonstrated by cooling the flue gas to 220-230°F at the ESP inlet via humidification. The host unit ESP operation was unaffected by the humidification and performed satisfactorily at low temperature conditions.

  16. Current oscillations in semi-insulating GaAs associated with field-enhanced capture of electrons by the major deep donor EL2

    NASA Technical Reports Server (NTRS)

    Kaminska, M.; Parsey, J. M.; Lagowski, J.; Gatos, H. C.

    1982-01-01

    Current oscillations thermally activated by the release of electrons from deep levels in undoped semiinsulating GaAs were observed for the first time. They were attributed to electric field-enhanced capture of electrons by the dominant deep donor EL2 (antisite AsGa defect). This enhanced capture is due to the configurational energy barrier of EL2, which is readily penetrated by hot electrons.

  17. Folate Functionalized Boron Nitride Nanotubes and their Selective Uptake by Glioblastoma Multiforme Cells: Implications for their Use as Boron Carriers in Clinical Boron Neutron Capture Therapy

    NASA Astrophysics Data System (ADS)

    Ciofani, Gianni; Raffa, Vittoria; Menciassi, Arianna; Cuschieri, Alfred

    2009-02-01

    Boron neutron capture therapy (BNCT) is increasingly being used in the treatment of several aggressive cancers, including cerebral glioblastoma multiforme. The main requirement for this therapy is selective targeting of tumor cells by sufficient quantities of 10B atoms required for their capture/irradiation with low-energy thermal neutrons. The low content of boron targeting species in glioblastoma multiforme accounts for the difficulty in selective targeting of this very malignant cerebral tumor by this radiation modality. In the present study, we have used for the first time boron nitride nanotubes as carriers of boron atoms to overcome this problem and enhance the selective targeting and ablative efficacy of BNCT for these tumors. Following their dispersion in aqueous solution by noncovalent coating with biocompatible poly- l-lysine solutions, boron nitride nanotubes were functionalized with a fluorescent probe (quantum dots) to enable their tracking and with folic acid as selective tumor targeting ligand. Initial in vitro studies have confirmed substantive and selective uptake of these nanovectors by glioblastoma multiforme cells, an observation which confirms their potential clinical application for BNCT therapy for these malignant cerebral tumors.

  18. Deformation field validation and inversion applied to adaptive radiation therapy

    NASA Astrophysics Data System (ADS)

    Vercauteren, Tom; De Gersem, Werner; Olteanu, Luiza A. M.; Madani, Indira; Duprez, Fréderic; Berwouts, Dieter; Speleers, Bruno; De Neve, Wilfried

    2013-08-01

    Development and implementation of chronological and anti-chronological adaptive dose accumulation strategies in adaptive intensity-modulated radiation therapy (IMRT) for head-and-neck cancer. An algorithm based on Newton iterations was implemented to efficiently compute inverse deformation fields (DFs). Four verification steps were performed to ensure a valid dose propagation: intra-cell folding detection finds zero or negative Jacobian determinants in the input DF; inter-cell folding detection is implemented on the resolution of the output DF; a region growing algorithm detects undefined values in the output DF; DF domains can be composed and displayed on the CT data. In 2011, one patient with nonmetastatic head and neck cancer selected from a three phase adaptive DPBN study was used to illustrate the algorithms implemented for adaptive chronological and anti-chronological dose accumulation. The patient received three 18F-FDG-PET/CTs prior to each treatment phase and one CT after finalizing treatment. Contour propagation and DF generation between two consecutive CTs was performed in Atlas-based autosegmentation (ABAS). Deformable image registration based dose accumulations were performed on CT1 and CT4. Dose propagation was done using combinations of DFs or their inversions. We have implemented a chronological and anti-chronological dose accumulation algorithm based on DF inversion. Algorithms were designed and implemented to detect cell folding.

  19. Acoustic and Cavitation Fields of Shock Wave Therapy Devices

    NASA Astrophysics Data System (ADS)

    Chitnis, Parag V.; Cleveland, Robin O.

    2006-05-01

    Extracorporeal shock wave therapy (ESWT) is considered a viable treatment modality for orthopedic ailments. Despite increasing clinical use, the mechanisms by which ESWT devices generate a therapeutic effect are not yet understood. The mechanistic differences in various devices and their efficacies might be dependent on their acoustic and cavitation outputs. We report acoustic and cavitation measurements of a number of different shock wave therapy devices. Two devices were electrohydraulic: one had a large reflector (HMT Ossatron) and the other was a hand-held source (HMT Evotron); the other device was a pneumatically driven device (EMS Swiss DolorClast Vet). Acoustic measurements were made using a fiber-optic probe hydrophone and a PVDF hydrophone. A dual passive cavitation detection system was used to monitor cavitation activity. Qualitative differences between these devices were also highlighted using a high-speed camera. We found that the Ossatron generated focused shock waves with a peak positive pressure around 40 MPa. The Evotron produced peak positive pressure around 20 MPa, however, its acoustic output appeared to be independent of the power setting of the device. The peak positive pressure from the DolorClast was about 5 MPa without a clear shock front. The DolorClast did not generate a focused acoustic field. Shadowgraph images show that the wave propagating from the DolorClast is planar and not focused in the vicinity of the hand-piece. All three devices produced measurable cavitation with a characteristic time (cavitation inception to bubble collapse) that varied between 95 and 209 μs for the Ossatron, between 59 and 283 μs for the Evotron, and between 195 and 431 μs for the DolorClast. The high-speed camera images show that the cavitation activity for the DolorClast is primarily restricted to the contact surface of the hand-piece. These data indicate that the devices studied here vary in acoustic and cavitation output, which may imply that the

  20. 1H and 10B NMR and MRI investigation of boron- and gadolinium-boron compounds in boron neutron capture therapy.

    PubMed

    Bonora, M; Corti, M; Borsa, F; Bortolussi, S; Protti, N; Santoro, D; Stella, S; Altieri, S; Zonta, C; Clerici, A M; Cansolino, L; Ferrari, C; Dionigi, P; Porta, A; Zanoni, G; Vidari, G

    2011-12-01

    (10)B molecular compounds suitable for Boron Neutron Capture Therapy (BNCT) are tagged with a Gd(III) paramagnetic ion. The newly synthesized molecule, Gd-BPA, is investigated as contrast agent in Magnetic Resonance Imaging (MRI) with the final aim of mapping the boron distribution in tissues. Preliminary Nuclear Magnetic Resonance (NMR) measurements, which include (1)H and (10)B relaxometry in animal tissues, proton relaxivity of the paramagnetic Gd-BPA molecule in water and its absorption in tumoral living cells, are reported.

  1. Combined use of sodium borocaptate and buthionine sulfoximine in boron neutron capture therapy enhanced tissue boron uptake and delayed tumor growth in a rat subcutaneous tumor model.

    PubMed

    Yoshida, Fumiyo; Yamamoto, Tetsuya; Nakai, Kei; Kumada, Hiroaki; Shibata, Yasushi; Tsuruta, Wataro; Endo, Kiyoshi; Tsurubuchi, Takao; Matsumura, Akira

    2008-05-18

    We have previously reported that buthionine sulfoximine (BSO) enhances sodium borocaptate (BSH) uptake by down regulating glutathione (GSH) synthesis in cultured cells. This study investigated the influence of BSO on tissue BSH uptake in vivo and the efficacy of BSH-BSO-mediated boron neutron capture therapy (BNCT) on tumor growth using a Fisher-344 rat subcutaneous tumor model. With BSO supplementation, boron uptake in subcutaneous tumor, blood, skin, muscle, liver, and kidney was significantly enhanced and maintained for 12h. Tumor growth was significantly delayed by using BSO. With further improvement in experimental conditions, radiation exposure time, together with radiation damage to normal tissues, could be reduced.

  2. Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: Trial using a lung metastasis model of CCS.

    PubMed

    Andoh, Tooru; Fujimoto, Takuya; Suzuki, Minoru; Sudo, Tamotsu; Sakurai, Yoshinori; Tanaka, Hiroki; Fujita, Ikuo; Fukase, Naomasa; Moritake, Hiroshi; Sugimoto, Tohru; Sakuma, Toshiko; Sasai, Hiroshi; Kawamoto, Teruya; Kirihata, Mitsunori; Fukumori, Yoshinobu; Akisue, Toshihiro; Ono, Koji; Ichikawa, Hideki

    2015-12-01

    Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In the present study, we established a lung metastasis animal model of CCS and investigated the therapeutic effect of boron neutron capture therapy (BNCT) using p-borono-L-phenylalanine (L-BPA). Biodistribution data revealed tumor-selective accumulation of (10)B. Unlike conventional gamma-ray irradiation, BNCT significantly suppressed tumor growth without damaging normal tissues, suggesting that it may be a potential new therapeutic option to treat CCS lung metastases.

  3. Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a (10)BSH-containing WOW emulsion.

    PubMed

    Yanagie, Hironobu; Higashi, Syushi; Seguchi, Koji; Ikushima, Ichiro; Fujihara, Mituteru; Nonaka, Yasumasa; Oyama, Kazuyuki; Maruyama, Syoji; Hatae, Ryo; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Tomoko; Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Narabayashi, Masaru; Kajiyama, Tetsuya; Maruhashi, Akira; Ono, Koji; Nakajima, Jun; Ono, Minoru; Takahashi, Hiroyuki; Eriguchi, Masazumi

    2014-06-01

    A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a (10)BSH-containing water-in-oil-in-water emulsion ((10)BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that (10)BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC.

  4. Optimum design and criticality safety of a beam-shaping assembly with an accelerator-driven subcritical neutron multiplier for boron neutron capture therapies.

    PubMed

    Hiraga, F

    2015-12-01

    The beam-shaping assembly for boron neutron capture therapies with a compact accelerator-driven subcritical neutron multiplier was designed so that an epithermal neutron flux of 1.9×10(9) cm(-2) s(-1) at the treatment position was generated by 5 MeV protons in a beam current of 2 mA. Changes in the atomic density of (135)Xe in the nuclear fuel due to the operation of the beam-shaping assembly were estimated. The criticality safety of the beam-shaping assembly in terms of Xe poisoning is discussed.

  5. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors. Technical progress report No. 1, May 1, 1990--January 31, 1991

    SciTech Connect

    Soloway, A.H.; Barth, R.F.

    1990-12-31

    Boron neutron capture therapy offers the potentiality for treating brain tumors currently resistant to treatment. The success of this form of therapy is directly dependent upon the delivery of sufficient numbers of thermal-neutrons to tumor cells which possess high concentrations of B-10. The objective of this project is to develop chemical methodology to synthesize boron-containing compounds with the potential for becoming incorporated into rapidly-dividing malignant brain tumor cells and excluded from normal components of the brain and surrounding tissues, to develope biological methods for assessing the potential of the compound by use of cell culture or intratumoral injection, to develop analytical methodology for measuring boron in cells and tissue using direct current plasma atomic emission spectroscopy (DCP-AES) and alpha track autoradiography, to develop biochemical and HPLC procedures for evaluating compound uptake and tissue half-life, and to develop procedures required to assess both in vitro and vivo efficacy of BNCT with selected compounds.

  6. Radiation transport requirements for clinical applications of neutron capture therapy: The rtt-MC Monte Carlo module

    SciTech Connect

    Wheeler, F.J.; Wessol, D.E.

    1995-12-31

    The rtt-MC dose calculation module of the BNCT-Rtpe treatment planning system has been developed specifically for boron neutron cancer therapy. Due to the complicated nature of combined gamma, fast-, epithermal- and thermal-energy neutron transport in tissue, all approaches to treatment planning to date for this treatment modality rely on Monte Carlo or three-dimensional discrete ordinates methods. Simple, fast and accurate methods for this modality have simply not been developed. In this paper the authors discuss some of the unique attributes of this therapy and the approaches they have used to begin to merge into clinical applications. As this paper is under draft, the modern implementation of boron neutron cancer therapy in the US is being realized. Research of skin and tumor effect for superficial melanoma of the extremities has been initiated at the Massachusetts Institute of Technology and brain cancer therapy (using this planning system) has begun at Brookhaven National Laboratory.

  7. The effects of ultra-strong magnetic fields on electron capture rates for iron group nuclei in the outer crust of magnetars

    NASA Astrophysics Data System (ADS)

    Du, Jun; Luo, Zhi-Quan; Zhang, Jie

    2014-06-01

    Based on the work of Wang et al. (Chin. Phys. Lett. 29:049701, 2012), we re-investigated electron capture on iron group nuclei in the outer crust of magnetars and studied magnetar evolution. Effects of ultra-strong magnetic field on electron capture rates for 57Co have been analyzed in the nuclear shell model and under the Landau-level-quantization approximation, and the electron capture rates and the neutrino energy loss rates on iron group nuclei in the outer crust of magnetar have been calculated. The results show that electron capture rates on 57Co are increase greatly in the ultra-strong magnetic field, and above 3 orders of magnitude generally; and the neutrino energy loss rates by electron capture on iron group nuclei increase above 3 orders of magnitude in the range from B=4.414×1013 G to B=4.414×1015 G. These conclusions play an important role in future studying the evolution of magnetar. Furthermore, we modify the expressions of the electron chemical potential (Fermi energy) and phase space factor by introducing Dirac δ-function, and select appropriate parameters of temperature T, magnetic field B and matter density ρ in the our crust, thus our results will be reliable than those of Wang et al.

  8. Evidence for field enhanced electron capture by EL2 centers in semi-insulating GaAs and the effect on GaAs radiation detectors

    SciTech Connect

    McGregor, D.S.; Rojeski, R.A.; Knoll, G.F. ); Terry, F.L. Jr.; East, J. ); Eisen, Y. )

    1994-06-15

    The performance of Schottky contact semiconductor radiation detectors fabricated from semi-insulating GaAs is highly sensitive to charged impurities and defects in the material. The observed behavior of semi-insulating GaAs Schottky barrier alpha particle detectors does not match well with models that treat the semi-insulating material as either perfectly intrinsic or as material with deep donors (EL2) of constant capture cross section compensated with shallow acceptors. We propose an explanation for the discrepancy based on enhanced capture of electrons by EL2 centers at high electric fields and the resulting formation of a quasineutral region in the GaAs. Presented is a simple model including field enhanced electron capture which shows good agreement with experimental alpha particle pulse height measurements.

  9. A microdosimetric study of {sup 10}B(n,{alpha}){sup 7}Li and {sup 157}Gd(n,{gamma}) reactions for neutron capture therapy

    SciTech Connect

    Wang, C.K.C.; Sutton, M.; Evans, T.M.; Laster, B.H.

    1996-12-31

    This paper presents the microdosimetric analysis for the most interesting cell survival experiment recently performed at the Brookhaven National Laboratory (BNL). In this experiment, the cells were first treated with a gadolinium (Gd) labeled tumor-seeking boronated porphyrin (Gd-BOPP) or with BOPP alone, and then irradiated with thermal neutrons. The resulting cell survival curves indicate that the {sup 157}Gd(n,{gamma}) reactions is very effective in cell killing. The death of a cell treated with GD-BOPP were attributed to either the {sup 10}B(n,{alpha}) {sup 7}Li reactions or the {sup 157}Gd(n,{gamma}) reactions (or both). However, the quantitative relationship between the two types of reaction and the cell survival fraction was not clear. This paper presents the microdosimetric analysis for the BNL experiment based on the measured experimental parameters, and the results clearly suggest a quantitative relationship between the two types of reaction and the cell survival fraction. The results also suggest new research in Gadolinium neutron capture therapy (GDNCT) which may lead to a more practical modality than the boron neutron capture therapy (BNCT) for treating cancers.

  10. A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.

    PubMed

    Alberti, Diego; Protti, Nicoletta; Toppino, Antonio; Deagostino, Annamaria; Lanzardo, Stefania; Bortolussi, Silva; Altieri, Saverio; Voena, Claudia; Chiarle, Roberto; Geninatti Crich, Simonetta; Aime, Silvio

    2015-04-01

    This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation.

  11. A microdosimetric study of {sup 10}B(n,{alpha}){sup 7}Li and {sup 157}Gd(n,{gamma}) reactions for neutron capture therapy

    SciTech Connect

    Wang, C.K.C.; Sutton, M.; Evans, T.M.; Laster, B.H.

    1999-01-01

    This paper presents the microdosimetric analysis for the most interesting cell survival experiment recently performed at the Brookhaven National Laboratory (BNL). In this experiment, the cells were first treated with a gadolinium (Gd) labeled tumor-seeking boronated porphyrin (Gd-BOPP) or with BOPP alone, and then irradiated with thermal neutrons. The resulting cell-survival curves indicate that the {sup 157}Gd(n,{gamma}) reactions are very effective in cell killing. The death of a cell treated with Gd-BOPP was attributed to either the {sup 10}B(n,{alpha}){sup 7}Li reactions or the {sup 157}Gd(n,{gamma}) reactions (or both). However, the quantitative relationship between the two types of reaction and the cell-survival fraction was not clear. This paper presents the microdosimetric analysis for the BNL experiment based on the measured experimental parameters, and the results clearly suggest a quantitative relationship between the two types of reaction and the cell survival fraction. The results also suggest new research in gadolinium neutron capture therapy (GdNCT) which may lead to a more practical modality than the boron neutron capture therapy (BNCT) for treating cancers.

  12. Boron neutron capture therapy using mixed epithermal and thermal neutron beams in patients with malignant glioma-correlation between radiation dose and radiation injury and clinical outcome

    SciTech Connect

    Kageji, Teruyoshi . E-mail: kageji@clin.med.tokushima-u.ac.jp; Nagahiro, Shinji; Matsuzaki, Kazuhito; Mizobuchi, Yoshifumi; Toi, Hiroyuki; Nakagawa, Yoshinobu; Kumada, Hiroaki

    2006-08-01

    Purpose: To clarify the correlation between the radiation dose and clinical outcome of sodium borocaptate-based intraoperative boron neutron capture therapy in patients with malignant glioma. Methods and Materials: The first protocol (P1998, n = 8) prescribed a maximal gross tumor volume (GTV) dose of 15 Gy. In 2001, a dose-escalated protocol was introduced (P2001, n 11), which prescribed a maximal vascular volume dose of 15 Gy or, alternatively, a clinical target volume (CTV) dose of 18 Gy. Results: The GTV and CTV doses in P2001 were 1.1-1.3 times greater than those in P1998. The maximal vascular volume dose of those with acute radiation injury was 15.8 Gy. The mean GTV and CTV dose in long-term survivors with glioblastoma was 26.4 and 16.5 Gy, respectively. A statistically significant correlation between the GTV dose and median survival time was found. In the 11 glioblastoma patients in P2001, the median survival time was 19.5 months and 1- and 2-year survival rate was 60.6% and 37.9%, respectively. Conclusion: Dose escalation contributed to the improvement in clinical outcome. To avoid radiation injury, the maximal vascular volume dose should be <12 Gy. For long-term survival in patients with glioblastoma after boron neutron capture therapy, the optimal mean dose of the GTV and CTV was 26 and 16 Gy, respectively.

  13. Spatial capture-recapture

    USGS Publications Warehouse

    Royle, J. Andrew; Chandler, Richard B.; Sollmann, Rahel; Gardner, Beth

    2013-01-01

    Spatial Capture-Recapture provides a revolutionary extension of traditional capture-recapture methods for studying animal populations using data from live trapping, camera trapping, DNA sampling, acoustic sampling, and related field methods. This book is a conceptual and methodological synthesis of spatial capture-recapture modeling. As a comprehensive how-to manual, this reference contains detailed examples of a wide range of relevant spatial capture-recapture models for inference about population size and spatial and temporal variation in demographic parameters. Practicing field biologists studying animal populations will find this book to be a useful resource, as will graduate students and professionals in ecology, conservation biology, and fisheries and wildlife management.

  14. Neutron capture therapy (NCT) enhancement of fast neutron radiotherapy: Application to non-small cell lung cancer

    NASA Astrophysics Data System (ADS)

    Laramore, G. E.; Stelzer, K. J.; Risler, R.; Schwartz, J. L.; Douglas, J. J.; Einck, J. P.; Nigg, D. W.; Wemple, C. A.; Hartwell, J. K.; Harker, Y. D.; Gavin, P. R.; Hawthorne, M. F.

    2001-07-01

    Fast neutron radiotherapy utilizes neutrons in the energy range of several millions to several tens of millions of eV to treat human malignancies. These fast neutron beams produce a small cloud of "slow" neutrons as they penetrate the body. If one can selectively attach isotopes having large neutron capture cross sections (such as 10B) to cancer cells, these "slow" neutrons can be used to enhance the killing of tumors. We describe a multidisciplinary effort to apply this technique to the treatment of patients with inoperable, non-small cell lung cancers. Problems in target design, compound development, beam optimization, and radiobiological experiments are discussed.

  15. Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

    SciTech Connect

    Coderre, J.A.; Chanana, A.D.; Joel, D.D.; Liu, H.B.; Slatkin, D.N.; Wielopolski, L.; Bergland, R.; Elowitz, E.; Chadha, M.

    1994-12-31

    The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report.

  16. Coordinated Control of Acoustical Field of View and Flight in Three-Dimensional Space for Consecutive Capture by Echolocating Bats during Natural Foraging.

    PubMed

    Sumiya, Miwa; Fujioka, Emyo; Motoi, Kazuya; Kondo, Masaru; Hiryu, Shizuko

    2017-01-01

    Echolocating bats prey upon small moving insects in the dark using sophisticated sonar techniques. The direction and directivity pattern of the ultrasound broadcast of these bats are important factors that affect their acoustical field of view, allowing us to investigate how the bats control their acoustic attention (pulse direction) for advanced flight maneuvers. The purpose of this study was to understand the behavioral strategies of acoustical sensing of wild Japanese house bats Pipistrellus abramus in three-dimensional (3D) space during consecutive capture flights. The results showed that when the bats successively captured multiple airborne insects in short time intervals (less than 1.5 s), they maintained not only the immediate prey but also the subsequent one simultaneously within the beam widths of the emitted pulses in both horizontal and vertical planes before capturing the immediate one. This suggests that echolocating bats maintain multiple prey within their acoustical field of view by a single sensing using a wide directional beam while approaching the immediate prey, instead of frequently shifting acoustic attention between multiple prey. We also numerically simulated the bats' flight trajectories when approaching two prey successively to investigate the relationship between the acoustical field of view and the prey direction for effective consecutive captures. This simulation demonstrated that acoustically viewing both the immediate and the subsequent prey simultaneously increases the success rate of capturing both prey, which is considered to be one of the basic axes of efficient route planning for consecutive capture flight. The bat's wide sonar beam can incidentally cover multiple prey while the bat forages in an area where the prey density is high. Our findings suggest that the bats then keep future targets within their acoustical field of view for effective foraging. In addition, in both the experimental results and the numerical simulations

  17. Coordinated Control of Acoustical Field of View and Flight in Three-Dimensional Space for Consecutive Capture by Echolocating Bats during Natural Foraging

    PubMed Central

    Sumiya, Miwa; Fujioka, Emyo; Motoi, Kazuya; Kondo, Masaru; Hiryu, Shizuko

    2017-01-01

    Echolocating bats prey upon small moving insects in the dark using sophisticated sonar techniques. The direction and directivity pattern of the ultrasound broadcast of these bats are important factors that affect their acoustical field of view, allowing us to investigate how the bats control their acoustic attention (pulse direction) for advanced flight maneuvers. The purpose of this study was to understand the behavioral strategies of acoustical sensing of wild Japanese house bats Pipistrellus abramus in three-dimensional (3D) space during consecutive capture flights. The results showed that when the bats successively captured multiple airborne insects in short time intervals (less than 1.5 s), they maintained not only the immediate prey but also the subsequent one simultaneously within the beam widths of the emitted pulses in both horizontal and vertical planes before capturing the immediate one. This suggests that echolocating bats maintain multiple prey within their acoustical field of view by a single sensing using a wide directional beam while approaching the immediate prey, instead of frequently shifting acoustic attention between multiple prey. We also numerically simulated the bats’ flight trajectories when approaching two prey successively to investigate the relationship between the acoustical field of view and the prey direction for effective consecutive captures. This simulation demonstrated that acoustically viewing both the immediate and the subsequent prey simultaneously increases the success rate of capturing both prey, which is considered to be one of the basic axes of efficient route planning for consecutive capture flight. The bat’s wide sonar beam can incidentally cover multiple prey while the bat forages in an area where the prey density is high. Our findings suggest that the bats then keep future targets within their acoustical field of view for effective foraging. In addition, in both the experimental results and the numerical simulations

  18. Efforts in Increasing Racial and Ethnic Diversity in the Field of Art Therapy

    ERIC Educational Resources Information Center

    Awais, Yasmine J.; Yali, Ann Marie

    2015-01-01

    There is a clear need for greater diversity in the field of art therapy, with a particular need to increase the representation of racial and ethnic minorities in educational programs. In a sample of 16 art therapy program directors, strategies and barriers to recruitment were identified through an anonymous online survey. The results of the survey…

  19. Anomalous Neutron Capture and Plastic Deformation of cu and pd Cathodes during Electrolysis in a Weak Thermalized Neutron Field:. Evidence of Nuclei-Lattice Exchange

    NASA Astrophysics Data System (ADS)

    Lipson, A. G.; Miley, G. H.; Lipson, A. G.

    2006-02-01

    Anomalous neutron capture and plastic deformation in the hardened Cu and Pd cathodes has been established under combined action of electrolysis and a weak thermalized neutron field (WTNF) with a flux in the range of 180-400 n/s cm2. Experiments with these cathodes showed ~7.0% decrease in the 2224 keV n-D gamma peak accompanying thermalized neutron capture inside the PE cavity during electrolysis vs. experiments with annealed Cu and Pd as well as with the background runs (i.e., no electrolysis). The anomalous neutron capture and plastic deformation of Cu and Pd cathodes under combined action of electrolysis and WTNF may be explained energetically by assuming a selective radiationless thermalized neutron capture at high-internal strain concentration sites in the hardened cathodes. The results of these experiments provide straightforward (avoids the Coulomb barrier penetration issue) evidence that nuclei-lattice energy exchange can result in an increase in neutron capture probability and radiationless de-excitation of the resulting compound nuclei.

  20. Controllability of depth dose distribution for neutron capture therapy at the Heavy Water Neutron Irradiation Facility of Kyoto University Research Reactor.

    PubMed

    Sakurai, Yoshinori; Kobayashi, Tooru

    2002-10-01

    The updating construction of the Heavy Water Neutron Irradiation Facility of the Kyoto University Research Reactor has been performed from November 1995 to March 1996 mainly for the improvement in neutron capture therapy. On the performance, the neutron irradiation modes with the variable energy spectra from almost pure thermal to epi-thermal neutrons became available by the control of the heavy-water thickness in the spectrum shifter and by the open-and-close of the cadmium and boral thermal neutron filters. The depth distributions of thermal, epi-thermal and fast neutron fluxes were measured by activation method using gold and indium, and the depth distributions of gamma-ray absorbed dose rate were measured using thermo-luminescent dosimeter of beryllium oxide for the several irradiation modes. From these measured data, the controllability of the depth dose distribution using the spectrum shifter and the thermal neutron filters was confirmed.

  1. Quantitative bioimaging of p-boronophenylalanine in thin liver tissue sections as a tool for treatment planning in boron neutron capture therapy.

    PubMed

    Reifschneider, Olga; Schütz, Christian L; Brochhausen, Christoph; Hampel, Gabriele; Ross, Tobias; Sperling, Michael; Karst, Uwe

    2015-03-01

    An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of 10B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of 10B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of 10B in cancerous and healthy tissue was carried out. Additionally, the distribution of 11B was investigated, providing 10B enrichment in the investigated tissues. Quantitative imaging of 10B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT.

  2. A conceptual design of a beam-shaping assembly for boron neutron capture therapy based on deuterium-tritium neutron generators.

    PubMed

    Martín, Guido; Abrahantes, Arian

    2004-05-01

    A conceptual design of a beam-shaping assembly for boron neutron capture therapy using deuterium-tritium accelerator based neutrons source is developed. Calculations based on a simple geometry model for the radiation transport are initially performed to estimate the assembly materials and their linear dimensions. Afterward, the assembly geometry is produced, optimized and verified. In order to perform these calculations the general-purpose MCNP code is used. Irradiation time and therapeutic gain are utilized as beam assessment parameters. Metallic uranium and manganese are successfully tested for fast-to-epithermal neutron moderation. In the present beam-shaping assembly proposal, the therapeutic gain is improved by 23% and the accelerator current required for a fixed irradiation period is reduced by six times compared to previous proposals based on the same D-T reaction.

  3. Specific killing effect of 10B1-para-boronophenylalanine in thermal neutron capture therapy of malignant melanoma: in vitro radiobiological evaluation

    SciTech Connect

    Ichihashi, M.; Nakanishi, T.; Mishima, Y.

    1982-03-01

    A 10B-dopa analogue, 10B1-para-boronophenylalanine (10B1-BPA) has been found to have a marked melanoma killing effect as expressed by the Do value, 0.9-1.2 X 10(12) n/cm2. The Do value of the neutron alone is 2.8 X 10(12) n/cm2. After the introduction of high LET irradiation into radiotherapy, its higher energy deposition in the target cancer cells is one of the major problems currently to be solved. This can be achieved by our thermal neutron capture therapy in the order of cellular dimensions when we have highly tumor-seeking 10B-compounds available. Our present evidence seems to indicate that our new 10B1-BPA can highly concentrate 10B into melanoma cells, to as much as 11 times the level of the medium in the in vitro system.

  4. Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via 1H2O MRI: implications for boron neutron capture therapy of malignant brain tumours

    NASA Astrophysics Data System (ADS)

    Medina, Daniel C.; Li, Xin; Springer, Charles S., Jr.

    2005-05-01

    In addition to its common usage as a tracer in metabolic and physiological studies, deuterium possesses anti-tumoural activity and confers protection against γ-irradiation. A more recent interest in deuterium emanates from the search for alternatives capable of improving neutron penetrance whilst reducing healthy tissue radiation dose deposition in boron neutron capture therapy of malignant brain tumours. Despite this potential clinical application, deuterium induces brain oedema, which is detrimental to neutron capture therapy. In this study, five adult male rats were titrated with deuterated drinking water while brain oedema was monitored via water proton magnetic resonance imaging. This report concludes that deuterium, as well as deuterium-induced brain oedema, possesses a uniform brain bio-distribution. At a steady-state blood fluid deuteration value of 16%, when the deuterium isotope fraction in drinking water was 25%, a mean oedematous volume change of 9 ± 2% (p-value <0.001) was observed in the rat brain—this may account for neurological and behavioural abnormalities found in mammals drinking highly deuterated water. In addition to characterizing the pharmaco-thermodynamics of deuterium-induced oedema, this report also estimates the impact of oedema on thermal neutron enhancement and effective dose reduction factors using simple linear transport calculations. While body fluid deuteration enhances thermal neutron flux penetrance and reduces dose deposition, oedema has the opposite effect because it increases the volume of interest, e.g., the brain volume. Thermal neutron enhancement and effective dose reduction factors could be reduced by as much as ~10% in the presence of a 9% water volume increase (oedema). All three authors have contributed equally to this work.

  5. Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via 1H2O MRI: implications for boron neutron capture therapy of malignant brain tumours.

    PubMed

    Medina, Daniel C; Li, Xin; Springer, Charles S

    2005-05-07

    In addition to its common usage as a tracer in metabolic and physiological studies, deuterium possesses anti-tumoural activity and confers protection against gamma-irradiation. A more recent interest in deuterium emanates from the search for alternatives capable of improving neutron penetrance whilst reducing healthy tissue radiation dose deposition in boron neutron capture therapy of malignant brain tumours. Despite this potential clinical application, deuterium induces brain oedema, which is detrimental to neutron capture therapy. In this study, five adult male rats were titrated with deuterated drinking water while brain oedema was monitored via water proton magnetic resonance imaging. This report concludes that deuterium, as well as deuterium-induced brain oedema, possesses a uniform brain bio-distribution. At a steady-state blood fluid deuteration value of 16%, when the deuterium isotope fraction in drinking water was 25%, a mean oedematous volume change of 9 +/- 2% (p-value <0.001) was observed in the rat brain-this may account for neurological and behavioural abnormalities found in mammals drinking highly deuterated water. In addition to characterizing the pharmaco-thermodynamics of deuterium-induced oedema, this report also estimates the impact of oedema on thermal neutron enhancement and effective dose reduction factors using simple linear transport calculations. While body fluid deuteration enhances thermal neutron flux penetrance and reduces dose deposition, oedema has the opposite effect because it increases the volume of interest, e.g., the brain volume. Thermal neutron enhancement and effective dose reduction factors could be reduced by as much as approximately 10% in the presence of a 9% water volume increase (oedema).

  6. The use of a robust capture-recapture design in small mammal population studies: A field example with Microtus pennsylvanicus

    USGS Publications Warehouse

    Nichols, J.D.; Pollock, K.H.; Hines, J.E.

    1984-01-01

    The robust design of Pollock (1982) was used to estimate parameters of a Maryland M. pennsylvanicus population. Closed model tests provided strong evidence of heterogeneity of capture probability, and model M eta (Otis et al., 1978) was selected as the most appropriate model for estimating population size. The Jolly-Seber model goodness-of-fit test indicated rejection of the model for this data set, and the M eta estimates of population size were all higher than the Jolly-Seber estimates. Both of these results are consistent with the evidence of heterogeneous capture probabilities. The authors thus used M eta estimates of population size, Jolly-Seber estimates of survival rate, and estimates of birth-immigration based on a combination of the population size and survival rate estimates. Advantages of the robust design estimates for certain inference procedures are discussed, and the design is recommended for future small mammal capture-recapture studies directed at estimation.

  7. Review of Narrative Therapy: Research and Utility.

    ERIC Educational Resources Information Center

    Etchison, Mary; Kleist, David M.

    2000-01-01

    Narrative therapy has captured the attention of many in the family counseling field. Despite the apparent appeal of narrative therapy as a therapeutic modality, research on its effectiveness is in its infancy. This article will review current research on narrative therapy and discuss why a broader research base has yet to be developed. Suggestions…

  8. Tumor-specific delivery of BSH-3R for boron neutron capture therapy and positron emission tomography imaging in a mouse brain tumor model.

    PubMed

    Iguchi, Yoshiya; Michiue, Hiroyuki; Kitamatsu, Mizuki; Hayashi, Yuri; Takenaka, Fumiaki; Nishiki, Tei-Ichi; Matsui, Hideki

    2015-07-01

    Glioblastoma, a malignant brain tumor with poor disease outcomes, is managed in modern medicine by multimodality therapy. Boron neutron capture therapy (BNCT) is an encouraging treatment under clinical investigation. In malignant cells, BNCT consists of two major factors: neutron radiation and boron uptake. To increase boron uptake in cells, we created a mercapto-closo-undecahydrododecaborate ([B12HnSH](2-)2Na(+), BSH) fused with a short arginine peptide (1R, 2R, 3R) and checked cellular uptake in vitro and in vivo. In a mouse brain tumor model, only BSH with at least three arginine domains could penetrate cell membranes of glioma cells in vitro and in vivo. Furthermore, to monitor the pharmacokinetic properties of these agents in vivo, we fused BSH and BSH-3R with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); DOTA is a metal chelating agent for labeling positron emission tomography (PET) probe with (64)Cu. We administered BSH-DOTA-(64)Cu and BSH-3R-DOTA-(64)Cu to the tumor model through a mouse tail vein and determined the drugs' pharmacokinetics by PET imaging. BSH-3R showed a high uptake in the tumor area on PET imaging. We concluded that BSH-3R is the ideal boron compound for clinical use during BNCT and that in developing this compound for clinical use, the BSH-3R PET probe is essential for pharmacokinetic imaging.

  9. Relative biological effects of neutron mixed-beam irradiation for boron neutron capture therapy on cell survival and DNA double-strand breaks in cultured mammalian cells

    PubMed Central

    Okumura, Kakuji; Kinashi, Yuko; Kubota, Yoshihisa; Kitajima, Erika; Okayasu, Ryuichi; Ono, Koji; Takahashi, Sentaro

    2013-01-01

    Understanding the biological effects of neutron mixed-beam irradiation used for boron neutron capture therapy (BNCT) is important in order to improve the efficacy of the therapy and to reduce side effects. In the present study, cell viability and DNA double-strand breaks (DNA-DSBs) were examined in Chinese hamster ovary cells (CHO-K1) and their radiosensitive mutant cells (xrs5, Ku80-deficient), following neutron mixed-beam irradiation for BNCT. Cell viability was significantly impaired in the neutron irradiation groups compared to the reference gamma-ray irradiation group. The relative biological effectiveness for 10% cell survival was 3.3 and 1.2 for CHO-K1 and xrs5 cells, respectively. There were a similar number of 53BP1 foci, indicators of DNA-DSBs, in the neutron mixed-beam and the gamma-ray groups. In addition, the size of the foci did not differ between groups. However, neutron mixed-beam irradiation resulted in foci with different spatial distributions. The foci were more proximal to each other in the neutron mixed-beam groups than the gamma-ray irradiation groups. These findings suggest that neutron beams may induce another type of DNA damage, such as clustered DNA-DSBs, as has been indicated for other high-LET irradiation. PMID:22966174

  10. Effect of anatomical variability on electric field characteristics of electroconvulsive therapy and magnetic seizure therapy: a parametric modeling study.

    PubMed

    Deng, Zhi-De; Lisanby, Sarah H; Peterchev, Angel V

    2015-01-01

    Electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) are conventionally applied with a fixed stimulus current amplitude, which may result in differences in the neural stimulation strength and focality across patients due to interindividual anatomical variability. The objective of this study is to quantify the effect of head anatomical variability associated with age, sex, and individual differences on the induced electric field characteristics in ECT and MST. Six stimulation modalities were modeled including bilateral and right unilateral ECT, focal electrically administered seizure therapy (FEAST), and MST with circular, cap, and double-cone coils. The electric field was computed using the finite element method in a parameterized spherical head model representing the variability in the general population. Head tissue layer thicknesses and conductivities were varied to examine the impact of interindividual anatomical differences on the stimulation strength, depth, and focality. Skull conductivity most strongly affects the ECT electric field, whereas the MST electric field is independent of tissue conductivity variation in this model but is markedly affected by differences in head diameter. Focal ECT electrode configurations such as FEAST is more sensitive to anatomical variability than that of less focal paradigms such as BL ECT. In MST, anatomical variability has stronger influence on the electric field of the cap and circular coils compared to the double-cone coil, possibly due to the more superficial field of the former. The variability of the ECT and MST electric fields due to anatomical differences should be considered in the interpretation of existing studies and in efforts to improve dosing approaches for better control of stimulation strength and focality across patients, such as individualization of the current amplitude. The conventional approach to individualizing dosage by titrating the number of pulses cannot compensate for differences in

  11. A Field Training Model for Creative Arts Therapies: Report from a 3-Year Program Evaluation

    ERIC Educational Resources Information Center

    Orkibi, Hod

    2012-01-01

    Clinical field training is an essential component of educating future therapists. This article discusses a creative arts therapies field training model in Israel as designed and modified from 3 years of program evaluation in a changing regulatory context. A clinical seminar structure puts beginning students in the role of participant-observer in…

  12. Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

    PubMed

    Dai, Congxin; Cai, Feng; Hwang, Kuo Chu; Zhou, Yongmao; Zhang, Zizhu; Liu, Xiaohai; Ma, Sihai; Yang, Yakun; Yao, Yong; Feng, Ming; Bao, Xinjie; Li, Guilin; Wei, Junji; Jiao, Yonghui; Wei, Zhenqing; Ma, Wenbin; Wang, Renzhi

    2013-02-01

    Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.

  13. Identification of Prey Captures in Australian Fur Seals (Arctocephalus pusillus doriferus) Using Head-Mounted Accelerometers: Field Validation with Animal-Borne Video Cameras

    PubMed Central

    Volpov, Beth L.; Hoskins, Andrew J.; Battaile, Brian C.; Viviant, Morgane; Wheatley, Kathryn E.; Marshall, Greg; Abernathy, Kyler; Arnould, John P. Y.

    2015-01-01

    This study investigated prey captures in free-ranging adult female Australian fur seals (Arctocephalus pusillus doriferus) using head-mounted 3-axis accelerometers and animal-borne video cameras. Acceleration data was used to identify individual attempted prey captures (APC), and video data were used to independently verify APC and prey types. Results demonstrated that head-mounted accelerometers could detect individual APC but were unable to distinguish among prey types (fish, cephalopod, stingray) or between successful captures and unsuccessful capture attempts. Mean detection rate (true positive rate) on individual animals in the testing subset ranged from 67-100%, and mean detection on the testing subset averaged across 4 animals ranged from 82-97%. Mean False positive (FP) rate ranged from 15-67% individually in the testing subset, and 26-59% averaged across 4 animals. Surge and sway had significantly greater detection rates, but also conversely greater FP rates compared to heave. Video data also indicated that some head movements recorded by the accelerometers were unrelated to APC and that a peak in acceleration variance did not always equate to an individual prey item. The results of the present study indicate that head-mounted accelerometers provide a complementary tool for investigating foraging behaviour in pinnipeds, but that detection and FP correction factors need to be applied for reliable field application. PMID:26107647

  14. Identification of Prey Captures in Australian Fur Seals (Arctocephalus pusillus doriferus) Using Head-Mounted Accelerometers: Field Validation with Animal-Borne Video Cameras.

    PubMed

    Volpov, Beth L; Hoskins, Andrew J; Battaile, Brian C; Viviant, Morgane; Wheatley, Kathryn E; Marshall, Greg; Abernathy, Kyler; Arnould, John P Y

    2015-01-01

    This study investigated prey captures in free-ranging adult female Australian fur seals (Arctocephalus pusillus doriferus) using head-mounted 3-axis accelerometers and animal-borne video cameras. Acceleration data was used to identify individual attempted prey captures (APC), and video data were used to independently verify APC and prey types. Results demonstrated that head-mounted accelerometers could detect individual APC but were unable to distinguish among prey types (fish, cephalopod, stingray) or between successful captures and unsuccessful capture attempts. Mean detection rate (true positive rate) on individual animals in the testing subset ranged from 67-100%, and mean detection on the testing subset averaged across 4 animals ranged from 82-97%. Mean False positive (FP) rate ranged from 15-67% individually in the testing subset, and 26-59% averaged across 4 animals. Surge and sway had significantly greater detection rates, but also conversely greater FP rates compared to heave. Video data also indicated that some head movements recorded by the accelerometers were unrelated to APC and that a peak in acceleration variance did not always equate to an individual prey item. The results of the present study indicate that head-mounted accelerometers provide a complementary tool for investigating foraging behaviour in pinnipeds, but that detection and FP correction factors need to be applied for reliable field application.

  15. Monte Carlo study of MLC fields for cobalt therapy machine

    PubMed Central

    Ayyangar, Komanduri M.; Rani, Roopa A.; Kumar, Anil; Reddy, A. R.

    2014-01-01

    An automated Multi-Leaf Collimator (MLC) system has been developed as add-on for the cobalt-60 teletherapy machines available in India. The goal of the present computational study is to validate the MLC design using Monte Carlo (MC) modeling. The study was based on the Kirloskar-supplied Phoenix model machines that closely match the Atomic Energy of Canada Limited (AECL) theratron-80 machine. The MLC is a retrofit attachment to the collimator assembly, with 14 non-divergent leaf pairs of 40 mm thick, 7 mm wide, and 150 mm long tungsten alloy plates with rounded edges and 20 mm tongue and 2 mm groove in each leaf. In the present work, the source and collimator geometry has been investigated in detail to arrive at a model that best represents the measured dosimetric data. The authors have studied in detail the proto-I MLC built for cobalt-60. The MLC field sizes were MC simulated for 2 × 2 cm2 to 14 × 14 cm2 square fields as well as irregular fields, and the percent depth dose (PDD) and profile data were compared with ROPS† treatment planning system (TPS). In addition, measured profiles using the IMATRIXX system‡ were also compared with the MC simulations. The proto-I MLC can define radiation fields up to 14 × 14 cm2 within 3 mm accuracy. The maximum measured leakage through the leaf ends in closed condition was 3.4% and interleaf leakage observed was 7.3%. Good agreement between MC results, ROPS and IMATRIXX results has been observed. The investigation also supports the hypothesis that optical and radiation field coincidence exists for the square fields studied with the MLC. Plots of the percent depth dose (PDD) data and profile data for clinically significant irregular fields have also been presented. The MC model was also investigated to speed up the calculations to allow calculations of clinically relevant conformal beams. †Radiation Oncology Planning System (ROPS) is supplied by Tirumala Jyothi Computer Systems described at https

  16. An Analysis of the Distribution and Economics of Oil Fields for Enhanced Oil Recovery-Carbon Capture and Storage

    NASA Astrophysics Data System (ADS)

    Hall, Kristyn Ann

    The rising carbon dioxide emissions contributing to climate change has lead to the examination of potential ways to mitigate the environmental impact. One such method is through the geological sequestration of carbon (CCS). Although there are several different forms of geological sequestration (i.e. Saline Aquifers, Oil and Gas Reservoirs, Unminable Coal Seams) the current projects are just initiating the large scale-testing phase. The lead entry point into CCS projects is to combine the sequestration with enhanced oil recovery (EOR) due to the improved economic model as a result of the oil recovery and the pre-existing knowledge of the geological structures. The potential scope of CCS-EOR projects throughout the continental United States in terms of a systematic examination of individual reservoir storage potential has not been examined. Instead the majority of the research completed has centered on either estimating the total United States storage potential or the potential of a single specific reservoir. The purpose of this paper is to examine the relationship between oil recovery, carbon dioxide storage and cost during CCS-EOR. The characteristics of the oil and gas reservoirs examined in this study from the Nehring Oil and Gas Database were used in the CCS-EOR model developed by Sean McCoy to estimate the lifting and storage costs of the different reservoirs throughout the continental United States. This allows for an examination of both technical and financial viability of CCS-EOR as an intermediate step for future CCS projects in other geological formations. One option for mitigating climate change is to store industrial CO2 emissions in geologic reservoirs as part of a process known as carbon capture and storage (CCS). There is general consensus that large-scale deployment of CCS would best be initiated by combining geologic sequestration with enhanced oil recovery (EOR), which can use CO2 to improve production from declining oil fields. Revenues from the

  17. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study

    NASA Astrophysics Data System (ADS)

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2011-02-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm-1 and 1.1-2.2 V cm-1 in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.

  18. Fission converter and metal-oxide-semiconductor field effect transistor study of thermal neutron flux distribution in an epithermal neutron therapy beam.

    PubMed

    Kaplan, G I; Rosenfeld, A B; Allen, B J; Coderre, J A; Liu, H B

    1999-09-01

    The depth distribution of the thermal neutron flux is a major factor in boron neutron capture therapy (BNCT) in determining the efficiency of cell sterilization. In this paper the fission detector method is developed and applied to measure the in-phantom thermal neutron flux depth distribution. Advantages of the fission detector include small size, direct measurement of thermal neutron flux in a mixed radiation field of BNCT beam, self-calibration, and the possibility of on-line measurement. The measurements were performed at epithermal a BNCT facility. The experimental results were compared with the thermal neutron flux calculated by the Monte Carlo method and found to be in good agreement.

  19. [Trental forte in leg ulcer therapy. Result of a field study].

    PubMed

    Weitgasser, H; Schmidt-Modrow, G

    1982-11-01

    In an open field study, 70 patients with leg ulcers, some existing already for a long time, were treated with Pentoxifylline in addition to the hitherto applied local therapy. The treatment usually comprised two months with a daily dosage of 800 mg up to 1200 mg (2 to 3 coated tablets Trental forte per day). More than 80% of patients with medium size ulcers could be cured by this therapy. The medicament was well tolerated.

  20. Trap capture of three economically important fruit fly species (Diptera: Tephritidae): evaluation of a solid formulation containing multiple male lures in a Hawaiian coffee field.

    PubMed

    Shelly, Todd; Nishimoto, Jon; Kurashima, Rick

    2012-08-01

    Invasive fruit flies (Diptera: Tephritidae) pose a global threat to agriculture through direct damage to food crops and the accompanying trade restrictions that often result. Early detection is vital to controlling fruit flies, because it increases the probability of limiting the growth and spread of the invasive population and thus may greatly reduce the monetary costs required for eradication or suppression. Male-specific lures are an important component of fruit fly detection, and three such lures are used widely: trimedlure (TML), cue lure (CL), and methyl eugenol (ME), attractive to Mediterranean fruit fly, Ceratitis capitata (Wiedemann); melon fly, Bactrocera cucurbitae (Coquillett); and oriental fruit fly, Bactrocera dorsalis (Hendel), respectively. In California, Florida, and Texas, the two Bactrocera lures are applied to separate species-specific traps as liquids (with a small amount of the insecticide naled added), whereas TML is delivered as a solid plug in another set of traps. Thus, the detection protocol involves considerable handling time as well as potential contact with a pesticide. The purpose of this study was to compare trap capture between liquid male lures and "trilure" wafers that contain TML, ME, raspberry ketone (RK, the hydroxy equivalent of CL), and the toxicant DDVP embedded within a solid matrix. Field studies were conducted in a Hawaiian coffee (Coffea arabica L.) field where the three aforementioned species co-occur, showed that the wafer captured at least as many flies as the liquid baits for all three species. This same result was obtained in comparisons using both fresh and aged (6-wk) baits. Moreover, the wafers performed as well as the single-lure traps in an ancillary experiment in which TML plugs were substituted for liquid TML. Additional experiments demonstrated explicitly that the presence of ME and RK had no effect on captures of C. capitata males and similarly that the presence of TML had no effect on the capture of B

  1. "Sequential” Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

    SciTech Connect

    Ana J. Molinari; Andrea Monti Hughes; Elisa M. Heber; Marcela A. Garabalino; Veronica A. Trivillin; Amanda E. Schwint; Emiliano C. C. Pozzi; Maria E. Itoiz; Silvia I. Thorp; Romina F. Aromando; David W. Nigg; Jorge Quintana; Gustavo A. Santa Cruz

    2011-04-01

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10B carriers in tumors followed by irradiation with a thermal or epithermal neutron beam. The minor abundance stable isotope of boron, 10B, interacts with low energy (thermal) neutrons to produce high linear energy transfer (LET) a-particles and 7Li ions. These disintegration products are known to have a high relative biological effectiveness (RBE). Their short range (<10 {micro}m) would limit the damage to cells containing 10B (1,2). Thus, BNCT would target tumor tissue selectively, sparing normal tissue. Clinical trials of BNCT for the treatment of glioblastoma multiforme and/or melanoma and, more recently, head and neck tumors and liver metastases, using boronophenylalanine (BPA) or sodium mercaptoundecahydrododecaborane (BSH) as the 10B carriers, have been performed or are underway in Argentina, Japan, the US and Europe (e.g. 3-8). To date, the clinical results have shown a potential, albeit inconclusive, therapeutic advantage for this technique. Contributory translational studies have been carried out employing a variety of experimental models based on the implantation of tumor cells in normal tissue (e.g. 5).

  2. Pharmacokinetics in melanoma-bearing mice of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a candidate compound for boron neutron capture therapy.

    PubMed

    Verrijk, R; Smolders, I J; Huiskamp, R; Gavin, P R; Philipp, K H; Begg, A C

    1994-04-01

    Blood pharmacokinetics and tissue distribution of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a boron carrier with postulated melanin-seeking properties for boron neutron capture therapy, were determined in C57/BL mice with subcutaneous pigmented or non-pigmented B16 melanomas. Borocaptate sodium (BSH) was used as a boron compound without melanin-seeking properties in a comparative biodistribution study in the same animal tumour models. Administration of single doses showed that BPTU was retained better in the pigmented B16 tumour than in the non-pigmented variant. BPTU was found in large concentrations in kidney and liver. Brain boron was approximately 10-fold lower than tumour boron. On a molar basis, BPTU demonstrated higher affinity for B16 tumours than BSH. Owing to solubility limits, tumour boron concentrations in this mouse study were too low for effective application of BNCT. However, the high tumour-to-blood and tumour-to-normal tissues ratios indicate that, with appropriate formulation, BPTU could be a promising candidate for clinical BNCT.

  3. “Sequential” Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

    SciTech Connect

    Ana J. Molinari; Emiliano C. C. Pozzi; Andrea Monti Hughes; Elisa M. Heber; Marcela A. Garabalino; Silvia I. Thorp; Marcelo Miller; Maria E. Itoiz; Romina F. Aromando; David W. Nigg; Jorge Quintana; Gustavo A. Santa Cruz; Veronica A. Trivillin; Amanda E. Schwint

    2011-04-01

    In the present study we evaluated the therapeutic effect and/or potential radiotoxicity of the novel “Tandem” Boron Neutron Capture Therapy (T-BNCT) for the treatment of oral cancer in the hamster cheek pouch model at RA-3 Nuclear Reactor. Two groups of animals were treated with “Tandem BNCT”, i.e. BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (T-24h-BNCT) or 48 h (T-48h-BNCT) later. A total tumor dose-matched single application of BNCT mediated by BPA and GB-10 administered jointly [(BPA + GB-10)-BNCT] was administered to an additional group of animals. At 28 days post-treatment, T-24h-BNCT and T-48h-BNCT induced, respectively, overall tumor control (OTC) of 95% and 91%, with no statistically significant differences between protocols. Tumor response for the single application of (BPA + GB-10)-BNCT was 75%, significantly lower than for T-BNCT. The T-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47% and 60% of the animals respectively. No normal tissue radiotoxicity was associated to tumor control for any of the protocols. “Tandem” BNCT enhances tumor control in oral cancer and reduces or, at worst, does not increase, mucositis in dose-limiting precancerous tissue.

  4. An irradiation facility for Boron Neutron Capture Therapy application based on a radio frequency driven D-T neutron source and a new beam shaping assembly

    NASA Astrophysics Data System (ADS)

    Cerullo, Nicola; Esposito, Juan; Leung, Ka Ngo; Custodero, Salvatore

    2002-10-01

    A line of the Boron Neutron Capture Therapy (BNCT) research program aimed at the treatment of brain tumors, carried on at the Nuclear Departments of Pisa and Genova Universities (DIMNP and DITEC), is being focused on a new, 3H(d,n)4He (D-T), accelerator-based neutron source concept, developed at Lawrence Berkeley National Laboratory (LBNL). Simple and compact accelerator designs, using mixed D+ T+ ion beam with relatively low energy, ˜100 keV, have been developed which, in turn, can generate high neutron yields. New approaches have thus been started to design an epithermal neutron irradiation facility able to selectively slow the 14.1 MeV D-T neutrons down to the epithermal (1 eV-10 KeV) energy range. New neutron spectrum shifter and filtering materials, as well as different facility layout approaches have been tested. Possible beam shaping assembly models have also been designed. The research demonstrates that a D-T neutron source could be successfully implemented to provide a ˜1×109 n/cm2 s epithermal neutron flux, in spite of its hard spectrum, although a generator device, able to yield ˜1014 n/s is, at present, not yet available. The latest Monte Carlo simulation of an accelerator-based facility, which relies on a single or multiple rf driven DT fusion neutron generator, is presented.

  5. "Sequential" boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model.

    PubMed

    Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Santa Cruz, Gustavo A; Trivillin, Verónica A; Schwint, Amanda E

    2011-04-01

    In the present study the therapeutic effect and potential toxicity of the novel "Sequential" boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with "Sequential" BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the "Sequential" BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 ± 2% and 91 ± 3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 ± 5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 ± 12% and 60 ± 22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. "Sequential" BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue.

  6. Demonstration of a high-intensity neutron source based on a liquid-lithium target for Accelerator based Boron Neutron Capture Therapy.

    PubMed

    Halfon, S; Arenshtam, A; Kijel, D; Paul, M; Weissman, L; Berkovits, D; Eliyahu, I; Feinberg, G; Kreisel, A; Mardor, I; Shimel, G; Shor, A; Silverman, I; Tessler, M

    2015-12-01

    A free surface liquid-lithium jet target is operating routinely at Soreq Applied Research Accelerator Facility (SARAF), bombarded with a ~1.91 MeV, ~1.2 mA continuous-wave narrow proton beam. The experiments demonstrate the liquid lithium target (LiLiT) capability to constitute an intense source of epithermal neutrons, for Accelerator based Boron Neutron Capture Therapy (BNCT). The target dissipates extremely high ion beam power densities (>3 kW/cm(2), >0.5 MW/cm(3)) for long periods of time, while maintaining stable conditions and localized residual activity. LiLiT generates ~3×10(10) n/s, which is more than one order of magnitude larger than conventional (7)Li(p,n)-based near threshold neutron sources. A shield and moderator assembly for BNCT, with LiLiT irradiated with protons at 1.91 MeV, was designed based on Monte Carlo (MCNP) simulations of BNCT-doses produced in a phantom. According to these simulations it was found that a ~15 mA near threshold proton current will apply the therapeutic doses in ~1h treatment duration. According to our present results, such high current beams can be dissipated in a liquid-lithium target, hence the target design is readily applicable for accelerator-based BNCT.

  7. Analysis of boron distribution in vivo for boron neutron capture therapy using two different boron compounds by secondary ion mass spectrometry.

    PubMed

    Yokoyama, Kunio; Miyatake, Shin-Ichi; Kajimoto, Yoshinaga; Kawabata, Shinji; Doi, Atsushi; Yoshida, Toshiko; Okabe, Motonori; Kirihata, Mitsunori; Ono, Koji; Kuroiwa, Toshihiko

    2007-01-01

    The efficiency of boron neutron capture therapy (BNCT) for malignant gliomas depends on the selective and absolute accumulation of (10)B atoms in tumor tissues. Only two boron compounds, BPA and BSH, currently can be used clinically. However, the detailed distributions of these compounds have not been determined. Here we used secondary ion mass spectrometry (SIMS) to determine the histological distribution of (10)B atoms derived from the boron compounds BSH and BPA. C6 tumor-bearing rats were given 500 mg/kg of BPA or 100 mg/kg of BSH intraperitoneally; 2.5 h later, their brains were sectioned and subjected to SIMS. In the main tumor mass, BPA accumulated heterogeneously, while BSH accumulated homogeneously. In the peritumoral area, both BPA and BSH accumulated measurably. Interestingly, in this area, BSH accumulated distinctively in a diffuse manner even 800 microm distant from the interface between the main tumor and normal brain. In the contralateral brain, BPA accumulated measurably, while BSH did not. In conclusion, both BPA and BSH each have advantages and disadvantages. These compounds are considered to be essential as boron delivery agents independently for clinical BNCT. There is some rationale for the simultaneous use of both compounds in clinical BNCT for malignant gliomas.

  8. Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

    PubMed

    Gao, Zhenyu; Horiguchi, Yukichi; Nakai, Kei; Matsumura, Akira; Suzuki, Minoru; Ono, Koji; Nagasaki, Yukio

    2016-10-01

    A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance.

  9. Monitoring oral temperature, heart rate, and respiration rate of West Indian manatees (Trichechus manatus) during capture and handling in the field

    USGS Publications Warehouse

    Wong, Arthur W.; Bonde, Robert K.; Siegal-Willott, Jessica; Stamper, M. Andrew; Colee, James; Powell, James A.; Reid, James P.; Deutsch, Charles J.; Harr, Kendal E.

    2012-01-01

    West Indian manatees (Trichechus manatus) are captured, handled, and transported to facilitate conservation, research, and rehabilitation efforts. Monitoring manatee oral temperature (OT), heart rate (HR), and respiration rate (RR) during out-of-water handling can assist efforts to maintain animal well-being and improve medical response to evidence of declining health. To determine effects of capture on manatee vital signs, we monitored OT, HR, and RR continuously for a 50-min period in 38 healthy, awake, juvenile and adult Florida manatees (T. m. latirostris) and 48 similar Antillean manatees (T. m. manatus). We examined creatine kinase (CK), potassium (K+), serum amyloid A (SAA), and lactate values for each animal to assess possible systemic inflammation and muscular trauma. OT range was 29.5 to 36.2° C, HR range was 32 to 88 beats/min, and RR range was 0 to 17 breaths/5 min. Antillean manatees had higher initial OT, HR, and RR than Florida manatees (p < 0.001). As monitoring time progressed, mean differences between the subspecies were no longer significant. High RR over monitoring time was associated with high lactate concentration. Antillean manatees had higher overall lactate values ([mean ± SD] 20.6 ± 7.8 mmol/L) than Florida manatees (13.7 ± 6.7 mmol/L; p < 0.001). We recommend monitoring manatee OT, HR, and RR during capture and handling in the field or in a captive care setting.

  10. Effects of Biogents Sentinel Trap Field Placement on Capture Rates of Adult Asian Tiger Mosquitoes, Aedes albopictus

    PubMed Central

    Crepeau, Taryn N.; Healy, Sean P.; Bartlett-Healy, Kristen; Unlu, Isik; Farajollahi, Ary; Fonseca, Dina M.

    2013-01-01

    The Biogents® Sentinel (BGS) trap is the standard tool to monitor adult Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae), the Asian tiger mosquito. BGS traps are commonly placed in residential properties during surveillance operations, but locations within properties may have significant differences in ambient light, temperature, and humidity (e.g. between a sunlit lawn and shady underbrush). We examined the effect of BGS trap placement on Ae. albopictus capture rates in three residential properties in Monmouth County, New Jersey, USA. In each property we visually selected locations as shade, partial shade, and sun. Traps in “partial shade” locations were under vegetation and were exposed to filtered sunlight during some parts of the day while “shaded” locations were never exposed to direct sunlight. Locations defined as “sun” were exposed to direct sunlight for large parts of the day. We placed a BGS trap in each of the three location types and used small data loggers to measure temperature, relative humidity, and light exposure at each trap during a 24-hour deployment. To address temporal variability, we made seven separate measurements from 31 August to 22 September 2010. We found that “partial shade” and “full shade” locations did not differ but that “full sun” locations had significantly higher light exposure, higher temperature, and lower humidity. Importantly, Ae. albopictus catches (males, females, or both) were consistently and significantly over 3 times higher in traps located in shaded locations. To further investigate the effects of local temperature and humidity on surveillance we examined Ae. albopictus collections from 37 BGS traps fitted with data loggers and deployed weekly from August through mid October, during the 2009 season, in three urban sites in Mercer County, NJ. We confirmed that local climate influences capture rates and that Ae. albopictus surveillance projects need to monitor trap placement carefully

  11. Case of glioblastoma patient treated with tumor treating fields therapy at recurrence degenerating to sarcoma.

    PubMed

    Majd, Pejman; O'Connell, Daniel E; Kim, Ronald C; Bota, Daniela A; Carrillo, Jose A

    2017-03-17

    Optune(®) treatment is a US FDA-approved treatment for glioblastoma (GBM) that employs alternating electric fields. Tumor treating field (TTF) therapy can exert its effects on GBM via cell cycle mitosis disruption and cytokinesis. We describe a patient with recurrent GBM who had disease progression following standard surgical treatment and concomitant chemoradiotherapy, and was found to have sarcomatous transformation after initiation of TTF therapy with bevacizumab. Upon tumor progression, repeat surgical resection revealed transformation into a GFAP-negative, reticulin-positive sarcoma with rhabdomyoid features. The possibility of a causal connection between TTF therapy and sarcomatous transformation needs to be further evaluated. No such case of apparent sarcoma formation in the CNS following chemoradiotherapy and/or TTF treatment for GBM has been reported.

  12. Families and Individual Development: Provocations from the Field of Family Therapy.

    ERIC Educational Resources Information Center

    Minuchin, Patricia

    1985-01-01

    Focuses on systems theory as the paradigm underlying family therapy and considers the implications of this framework for conceptions of the individual, the study of parent-child interaction, and new research formulations and areas of study. Considers trends in the developmental field that move toward such formulations. (RH)

  13. Capture of water-borne colloids in granular beds using external electric fields: improving removal of Cryptosporidium parvum.

    PubMed

    Kulkarni, Pramod; Dutari, Gabriel; Weingeist, David; Adin, Avner; Haught, Roy; Biswas, Pratim

    2005-03-01

    Suboptimal coagulation in water treatment plants often results in reduced removal efficiency of Cryptosporidium parvum oocysts by several orders of magnitude (J. AWWA 94(6) (2002) 97, J. AWWA 93(12) (2001) 64). The effect of external electric field on removal of C. parvum oocysts in packed granular beds was studied experimentally. A cylindrical configuration of electrodes, with granular media in the annular space was used. A negative DC potential was applied to the central electrode. No coagulants or flocculants were used and filtration was performed with and without application of an electric field to obtain improvement in removal efficiency. Results indicate that removal of C. parvum increased from 10% to 70% due to application of field in fine sand media and from 30% to 96% in MAGCHEM media. All other test particles (Kaolin and polystyrene latex microspheres) used in the study also exhibited increased removal in the presence of an electric field. Single collector efficiencies were also computed using approximate trajectory analysis, modified to account for the applied external electric field. The results of these calculations were used to qualitatively explain the trends in the experimental observations.

  14. Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

    SciTech Connect

    Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna; Saarilahti, Kauko; Atula, Timo; Collan, Juhani; Salli, Eero; Kortesniemi, Mika; Uusi-Simola, Jouni; Vaelimaeki, Petteri; Maekitie, Antti; Seppaenen, Marko; Minn, Heikki; Revitzer, Hannu; Kouri, Mauri; Kotiluoto, Petri; Seren, Tom; Auterinen, Iiro; Savolainen, Sauli; Joensuu, Heikki

    2012-01-01

    Purpose: To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy. Methods and Materials: In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by use of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%). Conclusions: Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent. Toxicity was

  15. Field match verification during combination proton, photon, and electron therapy for oligometastatic inflammatory breast cancer

    SciTech Connect

    Amos, Richard A.; Woodward, Wendy A.

    2012-01-01

    Postmastectomy radiation therapy (PMRT) has been shown in randomized trials to improve overall survival for patients with locally advanced breast cancer. The standard PMRT clinical target volume (CTV) encompasses the chest wall and undissected regional lymphatics. Conformal isodose distributions covering the standard CTV with acceptable dose limits to normal tissue can typically be achieved with a combination of photon and electron fields. Field borders are marked on the patient's skin using a light field projection of each beam and are subsequently used to verify daily field matching clinically. Initial imaging of a patient with oligometastatic inflammatory breast cancer demonstrated direct extension of disease from the involved internal mammary lymph node chain into the anterior mediastinum as the only site of metastatic disease. The patient achieved a pathologic complete response to neoadjuvant chemotherapy and underwent mastectomy. The initial sites of gross disease, including the anterior mediastinal node was included in the CTV for PMRT, and treatment planning demonstrated a clear advantage to the inclusion of proton fields in this case. The absence of a light source on the proton delivery system that accurately projects proton field edges onto the patient's skin posed a significant challenge for daily verification of proton-to-photon and -electron field matching. Proton field-specific radiographic imaging devices were designed and used such that proton field edges could be delineated on the patient's skin and used for daily matching with photon and electron fields. Manufacture of the imaging devices was quick and inexpensive. Weekly verification of proton field alignment with the proton field delineation on the skin demonstrated agreement within 3-mm tolerance. The patient remains with no evidence of disease 18 months after completing radiation. Other patients with similar indications may benefit from multimodality radiation therapy.

  16. Reactions and moderators for an accelerator-based epithermal neutron capture therapy source for cancer treatment. Final report, October 1900--September 1994

    SciTech Connect

    Kunze, J.F.; Brugger, R.M.

    1995-03-01

    The use of boron neutron capture therapy (BNCT) has been considered for nearly 30 years, and been practiced in Japan since the late 1970`s. Early experiments in the USA were generally nonpromising. However, new boron-containing ligand compounds were developed, which would seek out brain tumors. Concentration levels of the order of 30 micrograms of boron per gram of tissue become possible, and interest in the BNCT technique was revived in the USA beginning about 1985, with research reactors as the obvious source of the neutrons for the treatment. However, the limited number of research reactors in the USA (and the world) would mean that this treatment modality would be quite limited. The goals of this work was: (1) Examine as many as possible reactions of charged particles on various targets of an accelerator, and determine those that would give high neutron yields of a convenient energy. (2) Determine, through calculations (using Monte Carlo stochastic computer codes), the best design for a moderator/reflector assembly which would give high thermal flux at a nominal 5 cm depth in the head of a patient, with minimal radiation dose from gamma rays and fast neutrons. (3) Perform a benchmark experiment using a positive ion accelerator. The Li-7(p,n) reaction was chosen for the benchmark, since it was readily available for most accelerators, and was one of the two highest yielding reactions from Task No. 1. Since the University of Missouri has no accelerator, possible accelerators at other universities were investigated, as to availability and cost. A unit having capability in the 2.5 MeV range was desired.

  17. Radiation dose measurements and Monte Carlo calculations for neutron and photon reactions in a human head phantom for accelerator-based boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Kim, Don-Soo

    Dose measurements and radiation transport calculations were investigated for the interactions within the human brain of fast neutrons, slow neutrons, thermal neutrons, and photons associated with accelerator-based boron neutron capture therapy (ABNCT). To estimate the overall dose to the human brain, it is necessary to distinguish the doses from the different radiation sources. Using organic scintillators, human head phantom and detector assemblies were designed, constructed, and tested to determine the most appropriate dose estimation system to discriminate dose due to the different radiation sources that will ultimately be incorporated into a human head phantom to be used for dose measurements in ABNCT. Monoenergetic and continuous energy neutrons were generated via the 7Li(p,n)7Be reaction in a metallic lithium target near the reaction threshold using the 5.5 MV Van de Graaff accelerator at the University of Massachusetts Lowell. A human head phantom was built to measure and to distinguish the doses which result from proton recoils induced by fast neutrons, alpha particles and recoil lithium nuclei from the 10B(n,alpha)7Li reaction, and photons generated in the 7Li accelerator target as well as those generated inside the head phantom through various nuclear reactions at the same time during neutron irradiation procedures. The phantom consists of two main parts to estimate dose to tumor and dose to healthy tissue as well: a 3.22 cm3 boron loaded plastic scintillator which simulates a boron containing tumor inside the brain and a 2664 cm3 cylindrical liquid scintillator which represents the surrounding healthy tissue in the head. The Monte Carlo code MCNPX(TM) was used for the simulation of radiation transport due to neutrons and photons and extended to investigate the effects of neutrons and other radiation on the brain at various depths.

  18. Synthesis, Chemical and Enzymatic Hydrolysis, and Aqueous Solubility of Amino Acid Ester Prodrugs of 3-Carboranyl Thymidine Analogues for Boron Neutron Capture Therapy of Brain Tumors

    PubMed Central

    Hasabelnaby, Sherifa; Goudah, Ayman; Agarwal, Hitesh K.; Abd alla, Mosaad S. M.; Tjarks, Werner

    2012-01-01

    Various water-soluble L-valine-, L-glutamate-, and glycine ester prodrugs of two 3-Carboranyl Thymidine Analogues (3-CTAs), designated N5 and N5-2OH, were synthesized for Boron Neutron Capture Therapy (BNCT) of brain tumors since the water solubilities of the parental compounds proved to be insufficient in preclinical studies. The amino acid ester prodrugs were prepared and stored as hydrochloride salts. The water solubilities of these amino acid ester prodrugs, evaluated in phosphate buffered saline (PBS) at pH 5, pH 6 and pH 7.4, improved 48 to 6600 times compared with parental N5 and N5-2OH. The stability of the amino acid ester prodrugs was evaluated in PBS at pH 7.4, Bovine serum, and Bovine cerebrospinal fluid (CSF). The rate of the hydrolysis in all three incubation media depended primarily on the amino acid promoiety and, to a lesser extend, on the site of esterification at the deoxyribose portion of the 3-CTAs. In general, 3'-amino acid ester prodrugs were less sensitive to chemical and enzymatic hydrolysis than 5'-amino acid ester prodrugs and the stabilities of the latter decreased in the following order: 5'-valine > 5'-glutamate > 5'-glycine. The rate of the hydrolysis of the 5'-amino acid ester prodrugs in Bovine CSF was overall higher than in PBS and somewhat lower than in Bovine serum. Overall, 5'-glutamate ester prodrug of N5 and the 5'-glycine ester prodrugs of N5 and N5-2OH appeared to be the most promising candidates for preclinical BNCT studies. PMID:22889558

  19. Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model.

    PubMed

    Heber, Elisa M; Hawthorne, M Frederick; Kueffer, Peter J; Garabalino, Marcela A; Thorp, Silvia I; Pozzi, Emiliano C C; Monti Hughes, Andrea; Maitz, Charles A; Jalisatgi, Satish S; Nigg, David W; Curotto, Paula; Trivillin, Verónica A; Schwint, Amanda E

    2014-11-11

    The application of boron neutron capture therapy (BNCT) mediated by liposomes containing (10)B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%.

  20. Influence of Neutron Sources and 10B Concentration on Boron Neutron Capture Therapy for Shallow and Deeper Non-small Cell Lung Cancer.

    PubMed

    Yu, Haiyan; Tang, Xiaobin; Shu, Diyun; Liu, Yuanhao; Geng, Changran; Gong, Chunhui; Hang, Shuang; Chen, Da

    2017-03-01

    Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high Linear Energy Transfer (LET). It is considered a potential therapeutic approach for non-small cell lung cancer (NSCLC). It could avoid the inaccurate treatment caused by the lung motion during radiotherapy, because the dose deposition mainly depends on the boron localization and neutron source. Thus, B concentration and neutron sources are both principal factors of BNCT, and they play significant roles in the curative effect of BNCT for different cases. The purpose was to explore the feasibility of BNCT treatment for NSCLC with either of two neutron sources (the epithermal reactor at the Massachusetts Institute of Technology named "MIT source" and the accelerator neutron source designed in Argentina named "MEC source") and various boron concentrations. Shallow and deeper lung tumors were defined in the Chinese hybrid radiation phantom, and the Monte Carlo method was used to calculate the dose to tumors and healthy organs. The MEC source was more appropriate to treat the shallow tumor (depth of 6 cm) with a shorter treatment time. However, the MIT source was more suitable for deep lung tumor (depth of 9 cm) treatment, as the MEC source is more likely to exceed the skin dose limit. Thus, a neutron source consisting of more fast neutrons is not necessarily suitable for deep treatment of lung tumors. Theoretical distribution of B in tumors and organs at risk (especially skin) was obtained to meet the treatable requirement of BNCT, which may provide the references to identify the feasibility of BNCT for the treatment of lung cancer using these two neutron sources in future clinical applications.

  1. MRI-guided neutron capture therapy by use of a dual gadolinium/boron agent targeted at tumour cells through upregulated low-density lipoprotein transporters.

    PubMed

    Geninatti-Crich, Simonetta; Alberti, Diego; Szabo, Ibolya; Deagostino, Annamaria; Toppino, Antonio; Barge, Alessandro; Ballarini, Francesca; Bortolussi, Silva; Bruschi, Piero; Protti, Nicoletta; Stella, Sabrina; Altieri, Saverio; Venturello, Paolo; Aime, Silvio

    2011-07-18

    The upregulation of low-density lipoprotein (LDL) transporters in tumour cells has been exploited to deliver a sufficient amount of gadolinium/boron/ligand (Gd/B/L) probes for neutron capture therapy, a binary chemio-radiotherapy for cancer treatment. The Gd/B/L probe consists of a carborane unit (ten B atoms) bearing an aliphatic chain on one side (to bind LDL particles), and a Gd(III)/1,4,7,10-tetraazacyclododecane monoamide complex on the other (for detection by magnetic resonance imaging (MRI)). Up to 190 Gd/B/L probes were loaded per LDL particle. The uptake from tumour cells was initially assessed on cell cultures of human hepatoma (HepG2), murine melanoma (B16), and human glioblastoma (U87). The MRI assessment of the amount of Gd/B/L taken up by tumour cells was validated by inductively coupled plasma-mass-spectrometric measurements of the Gd and B content. Measurements were undertaken in vivo on mice bearing tumours in which B16 tumour cells were inoculated at the base of the neck. From the acquisition of magnetic resonance images, it was established that after 4-6 hours from the administration of the Gd/B/L-LDL particles (0.1 and 1 mmol kg(-1) of Gd and (10)B, respectively) the amount of boron taken up in the tumour region is above the threshold required for successful NCT treatment. After neutron irradiation, tumour growth was followed for 20 days by MRI. The group of treated mice showed markedly lower tumour growth with respect to the control group.

  2. Boron uptake in normal melanocytes and melanoma cells and boron biodistribution study in mice bearing B16F10 melanoma for boron neutron capture therapy.

    PubMed

    Faião-Flores, Fernanda; Coelho, Paulo Rogério Pinto; Arruda-Neto, João Dias Toledo; Camillo, Maria Aparecida Pires; Maria-Engler, Silvya Stuchi; Rici, Rose Eli Grassi; Sarkis, Jorge Eduardo Souza; Maria, Durvanei Augusto

    2012-08-01

    Information on (10)B distribution in normal tissues is crucial to any further development of boron neutron capture therapy (BNCT). The goal of this study was to investigate the in vitro and in vivo boron biodistribution in B16F10 murine melanoma and normal tissues as a model for human melanoma treatment by a simple and rapid colorimetric method, which was validated by HR-ICP-MS. The B16F10 melanoma cell line showed higher melanin content than human melanocytes, demonstrating a greater potential for boronophenylalanine uptake. The melanocytes showed a moderate viability decrease in the first few minutes after BNCT application, stabilizing after 75 min, whereas the B16F10 melanoma showed the greatest intracellular boron concentration at 150 min after application, indicating a different boron uptake of melanoma cells compared to normal melanocytes. Moreover, at this time, the increase in boron uptake in melanoma cells was approximately 1.6 times higher than that in normal melanocytes. The (10)B concentration in the blood of mice bearing B16F10 melanoma increased until 90 min after BNCT application and then decreased after 120 min, and remained low until the 240th minute. On the other hand, the (10)B concentration in tumors was increased from 90 min and maximal at 150 min after application, thus confirming the in vitro results. Therefore, the present in vitro and in vivo study of (10)B uptake in normal and tumor cells revealed important data that could enable BNCT to be possibly used as a treatment for melanoma, a chemoresistant cancer associated with high mortality.

  3. Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma.

    PubMed

    Perona, M; Rodríguez, C; Carpano, M; Thomasz, L; Nievas, S; Olivera, M; Thorp, S; Curotto, P; Pozzi, E; Kahl, S; Pisarev, M; Juvenal, G; Dagrosa, A

    2013-08-01

    We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated thyroid carcinoma (PDTC). Histone deacetylase inhibitors (HDACI) like sodium butyrate (NaB) cause hyperacetylation of histone proteins and show capacity to increase the gamma irradiation effect. The purpose of these studies was to investigate the use of the NaB as a radiosensitizer of the BNCT for PDTC. Follicular thyroid carcinoma cells (WRO) and rat thyroid epithelial cells (FRTL-5) were incubated with 1 mM NaB and then treated with boronophenylalanine ¹⁰BPA (10 μg ¹⁰B ml⁻¹) + neutrons, or with 2, 4-bis (α,β-dihydroxyethyl)-deutero-porphyrin IX ¹⁰BOPP (10 μg ¹⁰B ml⁻¹) + neutrons, or with a neutron beam alone. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux = (1.0 ± 0.1) × 10¹⁰ n cm⁻² s⁻¹). Cell survival decreased as a function of the physical absorbed dose in both cell lines. Moreover, the addition of NaB decreased cell survival (p < 0.05) in WRO cells incubated with both boron compounds. NaB increased the percentage of necrotic and apoptotic cells in both BNCT groups (p < 0.05). An accumulation of cells in G2/M phase at 24 h was observed for all the irradiated groups and the addition of NaB increased this percentage. Biodistribution studies of BPA (350 mg kg⁻¹ body weight) 24 h after NaB injection were performed. The in vivo studies showed that NaB treatment increases the amount of boron in the tumor at 2-h post-BPA injection (p < 0.01). We conclude that NaB could be used as a radiosensitizer for the treatment of thyroid carcinoma by BNCT.

  4. Selectivity of boron carriers for boron neutron capture therapy: pharmacological studies with borocaptate sodium, L-boronophenylalanine and boric acid in murine tumors.

    PubMed

    Gregoire, V; Begg, A C; Huiskamp, R; Verrijk, R; Bartelink, H

    1993-04-01

    Borocaptate sodium (BSH) and L-boronophenylalanine (L-BPA) are two boron carriers used for boron neutron capture therapy (BNCT) in the treatment of glioblastoma and melanoma, respectively. The suitability of these two compounds was evaluated on the basis of pharmacokinetic studies aiming at characterizing their biodistribution, tumor uptake and tumor selectivity. Boric acid was also used as a reference compound since it is nonselective and relatively freely diffusible. The compounds were investigated in two tumor models, a B16 pigmented melanoma and the RIF1 sarcoma. Mice were sacrificed after different boron doses at various post-injection times and tissue and plasma levels measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The proposed minimum effective tumor boron concentration of 15 ppm was achieved in both tumor models for the three compounds tested, although only for L-BPA in the melanoma was this achieved when tumor-plasma ratios were above 1. In the RIF1 model, maximum tumor concentrations of 44 and 31 ppm B were reached after administration of 50 micrograms B/g body weight for boric acid and BSH, respectively. After administration of 12.5 micrograms B/g of L-BPA, maximum concentrations of 15 and 21 ppm were found in the RIF1 and B16 models, respectively. Tumor-plasma ratios (TPR) for BSH remained close to or below unity at all times studied in both tumors. Brain levels of BSH were very low, however, leading to tumor-brain ratios markedly greater than 1 at all times. L-BPA and boric acid showed TPR values above unity in both tumor models, reaching 3.2 in B16.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. In vitro determination of uptake, retention, distribution, biological efficacy, and toxicity of boronated compounds for neutron capture therapy: a comparison of porphyrins with sulfhydryl boron hydrides.

    PubMed

    Fairchild, R G; Kahl, S B; Laster, B H; Kalef-Ezra, J; Popenoe, E A

    1990-08-15

    A major problem remaining in the evaluation of boronated compounds for neutron capture therapy (NCT) is the need to know the intra- or extracellular microdistribution of boron. This is a consequence of the short range of the 10B(n,alpha)7Li reaction products (approximately 10 microns), such that biological efficacy is dependent upon intracellular distribution. In particular, if boron location is predominantly extracellular, a significant reduction in efficacy would be expected. The in vitro procedure described here was developed mainly to provide information regarding the intra- and extracellular location and concentration of boron. However, use of the technique also allows the measurement of compound uptake and retention (binding) and the determination of biological efficacy by the evaluation of survival curves obtained following irradiation with thermal neutrons. Comparison is made to results obtained with boric acid (H3(10)BO3) and to results calculated for various boron distributions. Concomitantly, an indication of compound toxicity can be obtained from the plating efficiency of unirradiated control cells. Currently, most investigators utilize in vivo systems for testing and evaluating boron uptake from various carrier molecules. Given the large number of boron compounds being synthesized and needing evaluation as to their usefulness for NCT, the in vitro technique described here is simple and advantageous for initial compound screening. In addition to sparing animal lives, it is both time and cost effective and utilizes much smaller quantities of test compound than are required for an in vivo assay. A boronated porphyrin (BOPP) evaluated by the above procedure shows an uptake and retention approximately 20 times that of sulfhydryl boron hydride monomer (BSH); the latter compound is currently being used clinically for NCT in Japan and is anticipated for use in clinical trials in the United States. If the advantages demonstrated by BOPP in these in vitro

  6. Improvement of the tumor-suppressive effect of boron neutron capture therapy for amelanotic melanoma by intratumoral injection of the tyrosinase gene.

    PubMed

    Morita, Norimasa; Hiratsuka, Junichi; Kondoh, Hirohumi; Uno, Masako; Asano, Tomoyuki; Niki, Yoko; Sakurai, Yoshinori; Ono, Koji; Harada, Tamotsu; Imajo, Yoshinari

    2006-04-01

    Boron neutron capture therapy (BNCT) is successful when there is a sufficient (10)B concentration in tumor cells. In melanoma, (10)B-para-boronophenylalanine (BPA) accumulation is proportional to melanin-producing activity. This study was done to confirm enhancement of the tumor-suppressive effect of BNCT on amelanotic melanoma by intratumoral injection of the tyrosinase gene. D178 or FF amelanotic melanomas were implanted s.c. in Syrian hamsters. One group of D178- or FF-bearing hamsters (TD178 or TFF group) received intratumoral injections of pcDNA-Tyrs constructed as a tyrosinase expression plasmid. The other hamsters (pD178 and pFF groups) were injected with pUC119, and control hamsters (D178 and FF groups) only with transfection reagents. All the groups underwent immunofluorescence analysis of tyrosinase expression and BPA biodistribution studies. BNCT experiments were done at the Kyoto University Research Reactor. Tyrosinase expression increased in the tumors of the TD178 and TFF groups but remained the same in the pD178 and pFF groups. Tumor boron concentrations in the TD178 and TFF groups increased significantly (TD178: 49.7 +/- 12.6 versus D178: 27.2 +/- 4.9 microg/g, P < 0.0001; TFF: 30.7 +/- 6.6 versus FF: 13.0 +/- 4.7 microg/g, P < 0.0001). The BNCT tumor-suppressive effect was marked in the TD178 and TFF groups. In vivo transfection with the tyrosinase gene increased BPA accumulation in the tumors, the BNCT tumor-suppressive effect on amelanotic melanoma being significantly enhanced. These findings suggest a potential new clinical strategy for the treatment of amelanotic melanoma with BNCT.

  7. Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

    PubMed Central

    Heber, Elisa M.; Hawthorne, M. Frederick; Kueffer, Peter J.; Garabalino, Marcela A.; Thorp, Silvia I.; Pozzi, Emiliano C. C.; Hughes, Andrea Monti; Maitz, Charles A.; Jalisatgi, Satish S.; Nigg, David W.; Curotto, Paula; Trivillin, Verónica A.; Schwint, Amanda E.

    2014-01-01

    The application of boron neutron capture therapy (BNCT) mediated by liposomes containing 10B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70–88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70–88%. PMID:25349432

  8. A Classification of the Field of Family Therapy: A Review of Prior Attempts and a New Paradigmatic Model.

    ERIC Educational Resources Information Center

    Levant, Ronald F.

    1980-01-01

    Reviews early attempts to classify the field of family therapy, including Haley's caricatures, the Group for the Advancement of Psychiatry's classification, and others. The new paradigmatic model proposes a classification of the field of family therapy in terms of three therapeutic paradigms: the historical, the structure/process, and the…

  9. A robust procedure for verifying TomoTherapy Hi-Art™ source models for small fields

    NASA Astrophysics Data System (ADS)

    Hundertmark, B.; Sterpin, E.; Mackie, T.

    2011-06-01

    The dosimetric measurement and modeling of small radiation treatment fields (<2 × 2 cm2) are difficult to perform and prone to error. Measurements of small fields are often adversely influenced by the properties of the detectors used to make them. The dosimetric properties of small fields have been difficult to accurately model due to the effects of source occlusion caused by the collimating jaws. In this study, small longitudinal slice widths (SWs) of the TomoTherapy® Hi-Art® machine are characterized by performing dosimetric measurements topographically. By using a static gantry, opening the central 16 MLC leaves during the irradiations, and symmetrically scanning detectors 10 cm through each longitudinal SW, integral doses to a 'TomoTherapy equivalent' 10 × 10 cm2 area are topographically measured. To quantify the effects of source occlusion for TomoTherapy, a quantity referred to as the integral scanned dose to slice width ratio (D/SW) is introduced. (D/SW) ratios are measured for SWs ranging from 0.375 to 5 cm in size using ion chambers and a radiographic film. The measurements of the (D/SW) ratio are shown to be insensitive to the detectors used in this study. The (D/SW) ratios for TomoTherapy have values of unity in the range of SW sizes from 5 cm to approximately 2 cm. For SWs smaller than 2 cm in size, the source-occlusion effect substantially reduces the measured machine output and the value of the (D/SW) ratios. The topographic measurement method presented provides a way to directly evaluate the accuracy of the small-field source model parameters used in dose calculation algorithms. As an example, the electron source spot size of a Penelope Monte Carlo (MC) model of TomoTherapy was varied to match computed and measured (D/SW) ratios. It was shown that the MC results for small SW sizes were sensitive to that particular parameter.

  10. Tests of the Dynamic Field Theory and The Spatial Precision Hypothesis: Capturing a Qualitative Developmental Transition in Spatial Working Memory

    ERIC Educational Resources Information Center

    Schutte, Anne R.; Spencer, John P.

    2009-01-01

    This study tested a dynamic field theory (DFT) of spatial working memory and an associated spatial precision hypothesis (SPH). Between 3 and 6 years of age, there is a qualitative shift in how children use reference axes to remember locations: 3-year-olds' spatial recall responses are biased toward reference axes after short memory delays, whereas…

  11. Capture of non-target flies (Diptera: Lauxaniidae, Chloropidae, Anthomyiidae) on traps baited with volatile chemicals in field crop habitats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Volatile chemicals increased trap catch of flies from the families Lauxaniidae [Homoneura bispina (Loew) and Camptoprosopella borealis Shewell], Chloropidae (Olcella sp.) and Anthomyiidae (Delia spp.) in field crops. With cotton rolls as dispensers, baiting with 2-phenylethanol increased catch of H...

  12. Field capture of Thyanta perditor with pheromone-baited traps and cross-attraction to other pentatomids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Brazil, Thyanta perditor is one of the stink bugs attacking soybean and also could be found on others crops such as wheat, sunflower and sorghum. The objective of this work was to test the field attractiveness of traps baited with synthetic T. perditor pheromone. Two-liter transparent plastic sof...

  13. Matching Intensity-Modulated Radiation Therapy to an Anterior Low Neck Field

    SciTech Connect

    Amdur, Robert J. Liu, Chihray; Li, Jonathan; Mendenhall, William; Hinerman, Russell

    2007-10-01

    When using intensity-modulated radiation therapy (IMRT) to treat head and neck cancer with the primary site above the level of the larynx, there are two basic options for the low neck lymphatics: to treat the entire neck with IMRT, or to match the IMRT plan to a conventional anterior 'low neck' field. In view of the potential advantages of using a conventional low neck field, it is important to look for ways to minimize or manage the problems of matching IMRT to a conventional radiotherapy field. Treating the low neck with a single anterior field and the standard larynx block decreases the dose to the larynx and often results in a superior IMRT plan at the primary site. The purpose of this article is to review the most applicable studies and to discuss our experience with implementing a technique that involves moving the position of the superior border of the low neck field several times during a single treatment fraction.

  14. Validation of dosimetric field matching accuracy from proton therapy using a robotic patient positioning system.

    PubMed

    Farr, Jonathan B; O'Ryan-Blair, Avril; Jesseph, Frederick; Hsi, Wen-Chien; Allgower, Chris E; Mascia, Anthony E; Thornton, Allan F; Schreuder, Andreas N

    2010-04-12

    Large area, shallow fields are well suited to proton therapy. However, due to beam production limitations, such volumes typically require multiple matched fields. This is problematic due to the relatively narrow beam penumbra at shallow depths compared to electron and photon beams. Therefore, highly accurate dose planning and delivery is required. As the dose delivery includes shifting the patient for matched fields, accuracy at the 1-2 millimeter level in patient positioning is also required. This study investigates the dosimetric accuracy of such proton field matching by an innovative robotic patient positioner system (RPPS). The dosimetric comparisons were made between treatment planning system calculations, radiographic film and ionization chamber measurements. The results indicated good agreement amongst the methods and suggest that proton field matching by a RPPS is accurate and efficient.

  15. [Formation of optimum dose fields in contact radiation therapy of malignant tumors].

    PubMed

    Klepper, L Ia

    2003-01-01

    The definition of the homogeneity of a dose field in the contact radiation therapy for malignant tumors is introduced. The mathematical interpretation of problems in the formation of optimum dose fields, to which the maximum homogeneity of a dose field at the site of lesion corresponds, is presented. It is shown that the problems in the formation of optimum dose fields may be divided into two subsets in relation to whether the sources of radiation are located at the site of lesion or adjacent to the latter (application techniques of radiation). An analytical method for solving a problem in the formation of an optimal dose field in the ring circle by means of one ring source of radiation (the first type of problems). The investigation was conducted with the support of the Russian Fund of Fundamental Investigations (RFFI 01-01-00137).

  16. Muon capture in deuterium

    NASA Astrophysics Data System (ADS)

    Ricci, P.; Truhlík, E.; Mosconi, B.; Smejkal, J.

    2010-06-01

    Model dependence of the capture rates of the negative muon capture in deuterium is studied starting from potential models and the weak two-body meson exchange currents constructed in the tree approximation and also from an effective field theory. The tree one-boson exchange currents are derived from the hard pion chiral Lagrangians of the NΔπρωa system. If constructed in conjunction with the one-boson exchange potentials, the capture rates can be calculated consistently. On the other hand, the effective field theory currents, constructed within the heavy baryon chiral perturbation theory, contain a low energy constant d that cannot be extracted from data at the one-particle level nor determined from the first principles. Comparative analysis of the results for the doublet transition rate allows us to extract the constant d.

  17. Families and individual development: provocations from the field of family therapy.

    PubMed

    Minuchin, P

    1985-04-01

    Family therapy suggests a reformulation of concept and method in studying the family and individual development: to regard the family as an organized system and the individual as a contributing member, part of the process that creates and maintains the patterns that regulate behavior. In this review, the theories and clinical experiences of family therapists are regarded as a resource for developmental psychology, and particular attention is paid to those aspects that challenge traditional formulations in the developmental field. The review focuses on systems theory as the paradigm underlying family therapy and considers the implications of this framework for conceptions of the individual, the study of parent-child interaction, and new research formulations and areas of study. It also considers trends in the developmental field that move toward such formulations.

  18. Blood Meal Identification in Field-Captured Sand flies: Comparison of PCR-RFLP and ELISA Assays

    PubMed Central

    Maleki-Ravasan, N; Oshaghi, MA; Javadian, E; Rassi, Y; Sadraei, J; Mohtarami, F

    2009-01-01

    Background We aimed to develop a PCR-RFLP assay based on available sequences of putative vertebrate hosts to identify blood meals ingested by field female sand fly in the northwest of Iran. In addition, the utility of PCR-RFLP was compared with ELISA as a standard method. Methods: This experimental study was performed in the Insect Molecular Biology Laboratory of School of Public Health, Tehran University of Medical Sciences, Iran in 2006–2007. For PCR-RFLP a set of conserved vertebrate primers were used to amplify a part of the host mitochondrial cytochrome b (cyt b) gene followed by digestion of the PCR products by Hae III enzyme. Results: The PCR-RFLP and ELISA assays revealed that 34% and 27% of field-collected sand flies had fed on humans, respectively. Additionally, PCR-RFLP assays could reveal specific host DNA as well as the components of mixed blood meals. Results of PCR-RFLP assay showed that the sand flies had fed on cow (54%), human (10%), dog (4%), human and cow (21%), dog and cow (14%), and human and dog (3%). Conclusion: The results can provide a novel method for rapid diagnosis of blood meal taken by sandflies. The advantages and limitations of PCR and ELISA assays are discussed. PMID:22808367

  19. Feasibility of parenteral iron therapy as a field approach for management of pregnancy anaemia.

    PubMed

    Raman, L; Vasumathi, N; Rawal, A; Rajalakshmi, K

    1989-08-01

    The feasibility of parenteral iron administration for treatment of pregnancy anaemia, in field conditions was investigated. High reaction rates were observed (30-40%) with either intramuscular (im) or intravenous (iv) iron-dextran complex (test dose). Mothers with lower body weight had higher reaction rates with both im or iv iron-dextran complex. In pregnancy induced hypertension (PIH) the reaction rate was significantly lower. Our study indicates that under the existing situations of the health care system in India and the poor body weight and weight gain of Indian women during pregnancy, parenteral iron therapy for controlling anaemia may not be a feasible approach, at the field level.

  20. The local electric field favours more than exposed nitrogen atoms on CO2 capture: a case study on the rht-type MOF platform.

    PubMed

    Gao, Wen-Yang; Pham, Tony; Forrest, Katherine A; Space, Brian; Wojtas, Lukasz; Chen, Yu-Sheng; Ma, Shengqian

    2015-06-14

    Two rht-type metal-organic frameworks (MOFs) based upon the tetrazolate moiety and pyrazolate moiety, respectively, have been investigated for carbon dioxide (CO2) adsorption and selective adsorption of CO2 over CH4, which shows that the rht-MOF featuring the pyrazolate moiety demonstrates superior performances compared to the rht-MOF based on the tetrazolate moiety. In spite of more exposed nitrogen atoms in the tetrazolate-based rht-MOF, the counter-intuitive observations of CO2 capture in the two rht-MOFs were interpreted by computational studies, which reveal that the local electric field favours more than the richness of exposed nitrogen atoms for the interactions with CO2 molecules.

  1. Blood meal identification and parasite detection in laboratory-fed and field-captured Lutzomyia longipalpis by PCR using FTA databasing paper

    PubMed Central

    Sant’Anna, Mauricio R.V.; Jones, Nathaniel G.; Hindley, Jonathan A.; Mendes-Sousa, Antonio F.; Dillon, Rod J.; Cavalcante, Reginaldo R.; Alexander, Bruce; Bates, Paul A.

    2008-01-01

    The phlebotomine sand fly Lutzomyia longipalpis takes blood from a variety of wild and domestic animals and transmits Leishmania (Leishmania) infantum chagasi, etiological agent of American visceral leishmaniasis. Blood meal identification in sand flies has depended largely on serological methods but a new protocol described here uses filter-based technology to stabilise and store blood meal DNA, allowing subsequent PCR identification of blood meal sources, as well as parasite detection, in blood-fed sand flies. This technique revealed that 53.6% of field-collected sand flies captured in the back yards of houses in Teresina (Brazil) had fed on chickens. The potential applications of this technique in epidemiological studies and strategic planning for leishmaniasis control programmes are discussed. PMID:18606150

  2. Does Pulsed Magnetic Field Therapy Influence Nerve Regeneration in the Median Nerve Model of the Rat?

    PubMed Central

    Beck-Broichsitter, Benedicta E.; Lamia, Androniki; Fregnan, Federica; Smeets, Ralf; Becker, Stephan T.; Sinis, Nektarios

    2014-01-01

    The aim of this study was to evaluate the impact of pulsed magnetic field therapy on peripheral nerve regeneration after median nerve injury and primary coaptation in the rat. Both median nerves were surgically exposed and denervated in 24 female Wistar rats. A microsurgical coaptation was performed on the right side, whereas on the left side a spontaneous healing was prevented. The study group underwent a daily pulsed magnetic field therapy; the other group served as a control group. The grasping force was recorded 2 weeks after the surgical intervention for a period of 12 weeks. The right median nerve was excised and histologically examined. The histomorphometric data and the functional assessments were analyzed by t-test statistics and one-way ANOVA. One-way ANOVA indicated a statistically significant influence of group affiliation and grasping force (P = 0.0078). Grasping strength was higher on a significant level in the experimental group compared to the control group permanently from the 9th week to the end of the study. T-test statistics revealed a significantly higher weight of the flexor digitorum sublimis muscle (P = 0.0385) in the experimental group. The histological evaluation did not reveal any statistically significant differences concerning the histomorphometric parameters. Our results suggest that the pulsed magnetic field therapy has a positive influence on the functional aspects of neural regeneration. More studies are needed to precisely evaluate and optimize the intensity and duration of the application. PMID:25143937

  3. Use of conductive gels for electric field homogenization increases the antitumor efficacy of electroporation therapies

    NASA Astrophysics Data System (ADS)

    Ivorra, Antoni; Al-Sakere, Bassim; Rubinsky, Boris; Mir, Lluis M.

    2008-11-01

    Electroporation is used in tissue for gene therapy, drug therapy and minimally invasive tissue ablation. The electrical field that develops during the application of the high voltage pulses needs to be precisely controlled. In the region to be treated, it is desirable to generate a homogeneous electric field magnitude between two specific thresholds whereas in other regions the field magnitude should be as low as possible. In the case of irregularly shaped tissue structures, such as bulky tumors, electric field homogeneity is almost impossible to be achieved with current electrode arrangements. We propose the use of conductive gels, matched to the conductivity of the tissues, to fill dead spaces between plate electrodes gripping the tissue so that the electric field distribution becomes less heterogeneous. Here it is shown that this technique indeed improves the antitumor efficacy of electrochemotherapy in sarcomas implanted in mice. Furthermore, we analyze, through finite element method simulations, how relevant the conductivity mismatches are. We found that conductivity mismatching errors are surprisingly well tolerated by the technique. Gels with conductivities ranging from 5 mS cm-1 to 10 mS cm-1 will be a proper solution for most cases.

  4. Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

    SciTech Connect

    Carpano, Marina; Perona, Marina; Rodriguez, Carla; Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A.; Brandizzi, Daniel; Cabrini, Romulo; Pisarev, Mario; Juvenal, Guillermo Juan; Dagrosa, Maria Alejandra

    2015-10-01

    Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ({sup 10}BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10{sup 6} MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of {sup 10}B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37°C and 23°C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R{sup 2} = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R{sup 2} = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT

  5. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

    SciTech Connect

    David W. Nigg

    2012-05-01

    Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

  6. SU-E-J-100: Reconstruction of Prompt Gamma Ray Three Dimensional SPECT Image From Boron Neutron Capture Therapy(BNCT)

    SciTech Connect

    Yoon, D; Jung, J; Suh, T

    2014-06-01

    Purpose: Purpose of paper is to confirm the feasibility of acquisition of three dimensional single photon emission computed tomography (SPECT) image from boron neutron capture therapy (BNCT) using Monte Carlo simulation. Methods: In case of simulation, the pixelated SPECT detector, collimator and phantom were simulated using Monte Carlo n particle extended (MCNPX) simulation tool. A thermal neutron source (<1 eV) was used to react with the boron uptake region (BUR) in the phantom. Each geometry had a spherical pattern, and three different BURs (A, B and C region, density: 2.08 g/cm3) were located in the middle of the brain phantom. The data from 128 projections for each sorting process were used to achieve image reconstruction. The ordered subset expectation maximization (OSEM) reconstruction algorithm was used to obtain a tomographic image with eight subsets and five iterations. The receiver operating characteristic (ROC) curve analysis was used to evaluate the geometric accuracy of reconstructed image. Results: The OSEM image was compared with the original phantom pattern image. The area under the curve (AUC) was calculated as the gross area under each ROC curve. The three calculated AUC values were 0.738 (A region), 0.623 (B region), and 0.817 (C region). The differences between length of centers of two boron regions and distance of maximum count points were 0.3 cm, 1.6 cm and 1.4 cm. Conclusion: The possibility of extracting a 3D BNCT SPECT image was confirmed using the Monte Carlo simulation and OSEM algorithm. The prospects for obtaining an actual BNCT SPECT image were estimated from the quality of the simulated image and the simulation conditions. When multiple tumor region should be treated using the BNCT, a reasonable model to determine how many useful images can be obtained from the SPECT could be provided to the BNCT facilities. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research

  7. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential.

    PubMed

    Heber, Elisa M; Kueffer, Peter J; Lee, Mark W; Hawthorne, M Frederick; Garabalino, Marcela A; Molinari, Ana J; Nigg, David W; Bauer, William; Hughes, Andrea Monti; Pozzi, Emiliano C C; Trivillin, Verónica A; Schwint, Amanda E

    2012-05-01

    Boron neutron capture therapy (BNCT) combines selective accumulation of (10)B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na(3) [ae-B(20)H(17)NH(3)], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

  8. SU-E-T-21: A D-D Based Neutron Generator System for Boron Neutron Capture Therapy: A Feasibility Study

    SciTech Connect

    Hsieh, M; Liu, Y; Nie, L

    2015-06-15

    Purpose: To investigate the feasibility of a deuterium-deuterium (DD) neutron generator for application in boron neutron capture therapy (BNCT) of brain cancer Methods: MCNP simulations were performed using a head phantom and a monoenergetic neutron source, which resembles the point source in a DD generator that emits 2.45-MeV neutrons. Source energies ranging from 5eV to 2.45MeV were simulated to determine the optimal treatment energy. The phantom consisted of soft tissue, brain tissue, skull, skin layer, and a brain tumor of 5 cm in diameter. Tumor depth was varied from 5–10 cm. Boron-10 concentrations of 10 ppm, 15 ppm, and 30 ppm were used in the soft/brain tissues, skin, and tumor, respectively. The neutron flux required to deliver 60 Gy to the tumor as well as the normal tissue doses were determined. Results: Beam energies between 5eV and 10keV obtained doses with the highest dose ratios (3.3–25.9) between the tumor and the brain at various depths. The dose ratio with 2.45-MeV neutrons ranged from 0.8–6.6. To achieve the desired tumor dose in 40 minutes, the required neutron flux for a DD generator was between 8.8E10 and 5.2E11 n/s and the resulting brain dose was between 2.3 and 18 Gy, depending on the tumor depth. The skin and soft tissue doses were within acceptable tolerances. The boron-neutron interaction accounted for 54–58% of the total dose. Conclusion: This study shows that the DD neutron generator can be a feasible neutron source for BNCT. The required neutron flux for treatment is achievable with the current DD neutron technology. With a well-designed beam shaping assembly and treatment geometry, the neutron flux can be further improved and a 60-Gy prescription can be accurately delivered to the target while maintaining tolerable normal tissue doses. Further experimental studies will be developed and conducted to validate the simulation results.

  9. Chromosomal Aberrations in Large Japanese Field Mice (Apodemus speciosus) Captured near Fukushima Dai-ichi Nuclear Power Plant.

    PubMed

    Kawagoshi, Taiki; Shiomi, Naoko; Takahashi, Hiroyuki; Watanabe, Yoshito; Fuma, Shoichi; Doi, Kazutaka; Kawaguchi, Isao; Aoki, Masanari; Kubota, Masahide; Furuhata, Yoshiaki; Shigemura, Yusaku; Mizoguchi, Masahiko; Yamada, Fumio; Tomozawa, Morihiko; Sakamoto, Shinsuke H; Yoshida, Satoshi; Kubota, Yoshihisa

    2017-04-07

    Since the Fukushima Dai-ichi Nuclear Power Plant accident, radiation effects on nonhuman biota in the contaminated areas have been a major concern. Here, we analyzed the frequencies of chromosomal aberrations (translocations and dicentrics) in the splenic lymphocytes of large Japanese field mice (Apodemus speciosus) inhabiting Fukushima Prefecture. A. speciosus chromosomes 1, 2, and 5 were flow-sorted in order to develop A. speciosus chromosome-specific painting probes, and FISH (fluorescence in situ hybridization) was performed using these painting probes to detect the translocations and dicentrics. The average frequency of the translocations and dicentrics per cell in the heavily contaminated area was significantly higher than the frequencies in the case of the noncontaminated control area and the slightly and moderately contaminated areas, and this aberration frequency in individual mice tended to roughly increase with the estimated dose rates and accumulated doses. In all four sampling areas, the proportion of aberrations occurring in chromosome 2 was approximately >3 times higher than that in chromosomes 1 and 5, which suggests that A. speciosus chromosome 2 harbors a fragile site that is highly sensitive to chromosome breaks induced by cellular stress such as DNA replication. The elevated frequency of chromosomal aberrations in A. speciosus potentially resulting from the presence of a fragile site in chromosome 2 might make it challenging to observe the mild effect of chronic low-dose-rate irradiation on the induction of chromosomal aberrations in A. speciosus inhabiting the contaminated areas of Fukushima.

  10. Water quality evaluation of two interconnected dam lakes with field-captured and laboratory-acclimated fish, Cyprinus carpio.

    PubMed

    Güngördü, Abbas; Ozmen, Murat

    2012-01-01

    Karakaya and Sultansuyu Dam Lakes, located in the eastern part of Turkey, are important water sources, both for irrigation and fishery. The main goal of the study was to investigate water qualities of dam lakes using a set of biomarkers in the fish Cyprinus carpio. For this aim, field sample and laboratory-acclimated fish were compared to identify changes in selected biomarkers. The activities of ethoxyresorufin-O-deethylase, glutathione S-transferase, glutathione reductase, and carboxylesterase were determined in liver samples. Also, plasma and liver lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase activities were assayed. Brain acetylcholinesterase and carboxylesterase activities were also determined. The hepatosomatic index and condition factors were calculated. Plasma vitellogenin assays were evaluated for the presence of xenoestrogen. Physicochemical values of water samples showed the existence of eutrophication risk, and also, some chemicals in both lakes were determined to be over tolerable limits. The comparisons of samples from both dam lake and laboratory-acclimated fish showed that the lakes may be at risk of pollution by some xenobiotics, namely xenoestrogens and acetylcholinesterase-inhibiting agents.

  11. US Spacesuit Knowledge Capture

    NASA Technical Reports Server (NTRS)

    Chullen, Cinda; Thomas, Ken; McMann, Joe; Dolan, Kristi; Bitterly, Rose; Lewis, Cathleen

    2011-01-01

    The ability to learn from both the mistakes and successes of the past is vital to assuring success in the future. Due to the close physical interaction between spacesuit systems and human beings as users, spacesuit technology and usage lends itself rather uniquely to the benefits realized from the skillful organization of historical information; its dissemination; the collection and identification of artifacts; and the education of those in the field. The National Aeronautics and Space Administration (NASA), other organizations and individuals have been performing United States (U.S.) Spacesuit Knowledge Capture since the beginning of space exploration. Avenues used to capture the knowledge have included publication of reports; conference presentations; specialized seminars; and classes usually given by veterans in the field. More recently the effort has been more concentrated and formalized whereby a new avenue of spacesuit knowledge capture has been added to the archives in which videotaping occurs engaging both current and retired specialists in the field presenting technical scope specifically for education and preservation of knowledge. With video archiving, all these avenues of learning can now be brought to life with the real experts presenting their wealth of knowledge on screen for future learners to enjoy. Scope and topics of U.S. spacesuit knowledge capture have included lessons learned in spacesuit technology, experience from the Gemini, Apollo, Skylab and Shuttle programs, hardware certification, design, development and other program components, spacesuit evolution and experience, failure analysis and resolution, and aspects of program management. Concurrently, U.S. spacesuit knowledge capture activities have progressed to a level where NASA, the National Air and Space Museum (NASM), Hamilton Sundstrand (HS) and the spacesuit community are now working together to provide a comprehensive closed-looped spacesuit knowledge capture system which includes

  12. A hybrid actuated microrobot using an electromagnetic field and flagellated bacteria for tumor-targeting therapy.

    PubMed

    Li, Donghai; Choi, Hyunchul; Cho, Sunghoon; Jeong, Semi; Jin, Zhen; Lee, Cheong; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

    2015-08-01

    In this paper, we propose a new concept for a hybrid actuated microrobot for tumor-targeting therapy. For drug delivery in tumor therapy, various electromagnetic actuated microrobot systems have been studied. In addition, bacteria-based microrobot (so-called bacteriobot), which use tumor targeting and the therapeutic function of the bacteria, has also been proposed for solid tumor therapy. Compared with bacteriobot, electromagnetic actuated microrobot has larger driving force and locomotive controllability due to their position recognition and magnetic field control. However, because electromagnetic actuated microrobot does not have self-tumor targeting, they need to be controlled by an external magnetic field. In contrast, the bacteriobot uses tumor targeting and the bacteria's own motility, and can exhibit self-targeting performance at solid tumors. However, because the propulsion forces of the bacteria are too small, it is very difficult for bacteriobot to track a tumor in a vessel with a large bloodstream. Therefore, we propose a hybrid actuated microrobot combined with electromagnetic actuation in large blood vessels with a macro range and bacterial actuation in small vessels with a micro range. In addition, the proposed microrobot consists of biodegradable and biocompatible microbeads in which the drugs and magnetic particles can be encapsulated; the bacteria can be attached to the surface of the microbeads and propel the microrobot. We carried out macro-manipulation of the hybrid actuated microrobot along a desired path through electromagnetic field control and the micro-manipulation of the hybrid actuated microrobot toward a chemical attractant through the chemotaxis of the bacteria. For the validation of the hybrid actuation of the microrobot, we fabricated a hydrogel microfluidic channel that can generate a chemical gradient. Finally, we evaluated the motility performance of the hybrid actuated microrobot in the hydrogel microfluidic channel. We expect

  13. Magnetic-field-assisted photothermal therapy of cancer cells using Fe-doped carbon nanoparticles

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Vardarajan, Vijaylakshmi; Koymen, Ali R.; Mohanty, Samarendra K.

    2012-01-01

    Photothermal therapy with assistance of nanoparticles offers a solution for the destruction of cancer cells without significant collateral damage to otherwise healthy cells. However, minimizing the required number of injected nanoparticles is a major challenge. Here, we introduce the use of magnetic carbon nanoparticles (MCNPs), localizing them in a desired region by applying an external magnetic-field, and irradiating the targeted cancer cells with a near-infrared laser beam. The MCNPs were prepared in benzene, using an electric plasma discharge, generated in the cavitation field of an ultrasonic horn. The CNPs were made ferromagnetic by use of Fe-electrodes to dope the CNPs, as confirmed by magnetometry. Transmission electron microscopy measurements showed the size distribution of these MCNPs to be in the range of 5 to 10 nm. For photothermal irradiation, a tunable continuous wave Ti: Sapphire laser beam was weakly focused on to the cell monolayer under an inverted fluorescence microscope. The response of different cell types to photothermal irradiation was investigated. Cell death in the presence of both MCNPs and laser beam was confirmed by morphological changes and propidium iodide fluorescence inclusion assay. The results of our study suggest that MCNP based photothermal therapy is a promising approach to remotely guide photothermal therapy.

  14. The management of intractable pain with adjuvant pulsed electromagnetic field therapy.

    PubMed

    Niezgoda, Jeffrey A; Hardin, Scott T; Kubat, Nicole; Acompanado, Jocelyn

    2014-05-01

    This case describes a 51-year-old woman who reported experiencing severe, constant pain, diffusely located in the region of her right mandible neck (primarily involving the mandible, lower right molars, the neck, the upper back, and the shoulder) during the course of several years. Surgical interventions (root canal, spinal fusion) were performed to address potential sources of pain. Despite these interventions, the patient reported severe pain after both surgeries, which persisted beyond the acute postoperative period. Additional pharmacological interventions and physical therapy were also attempted; nonetheless, the patient reported that pain remained severe and constant for approximately 2 years. On the basis of the patient's poor response to conventional treatments, a novel approach of botulinum toxin (BTX) injections was initiated. When pulsed electromagnetic field therapy was added, the need for BTX injections decreased, with the patient reporting a noticeable decrease in pain intensity and an improvement in quality of life measures. Currently, the patient continues to use pulsed electromagnetic field therapy regularly for pain management, which has allowed her to reduce the use of other interventions and avoid continued use of narcotic medications. Considering the need for multifaceted pain management approaches in the treatment of chronic pain, this case is relevant for wound care practitioners attending to patients with chronic postincisional wound pain because the outcome highlights the utility of a nonpharmacological, complementary pain management intervention for closed, yet persistently painful, postoperative wounds.

  15. Fractionated Wide-Field Radiation Therapy Followed by Fractionated Local-Field Irradiation for Treating Widespread Painful Bone Metastasis

    SciTech Connect

    Ki, Yongkan; Kim, Wontaek; Nam, Jiho; Kim, Donghyun; Jeon, Hosang; Park, Dahl; Kim, Dongwon

    2011-01-01

    Purpose: Wide-field radiation therapy (WFRT) is an effective treatment for widespread bone metastasis. We evaluated local-field irradiation (LFI) after fractionated WFRT (f-WFRT) for treating the patients with multiple painful bone lesions. Methods and Materials: From 1998 to 2007, 32 patients with multiple bone metastases were treated with fractionated LFI (f-LFI) after f-WFRT. All patients initially received 15 Gy in 5 fractions to a wide field, followed by LFI (9-15 Gy in 3 Gy fractions). Response was assessed by evaluating the degree of pain relief using a visual analog scale before radiotherapy, after f-WFRT, and after f-LFI. Results: Fractionated LFI following f-WFRT yielded an overall relief rate of 93.8% and a complete relief rate of 43.8%. The rate of the appearance of new disease was 6.3% for the patients with complete relief, 20.5% for the patients with a partial relief, and 50% for the patients with no relief. Conclusion: Fractionated LFI after f-WFRT is a well-tolerated and effective treatment for multiple metastatic bone disease.

  16. Local and Global Impacts of Carbon Capture and Storage Combined with Enhanced Oil Recovery in Four Depleted Oil Fields, Kern County, California

    NASA Astrophysics Data System (ADS)

    Gillespie, J.; Jordan, P. D.; Goodell, J. A.; Harrington, K.; Jameson, S.

    2015-12-01

    Depleted oil reservoirs are attractive targets for geologic carbon storage (GCS) because they possess proven trapping mechanisms and large amounts of data pertaining to production and reservoir geometry. In addition, CO2 enhanced oil recovery (EOR) can improve recovery of the remaining oil at recovery factors of 6 to 20% of original oil in place in appropriate reservoirs. CO2 EOR increases the attractiveness of depleted oil and gas reservoirs as a starting point for CCS because the CO2 becomes a commodity that can be purchased by field operators for EOR purposes thereby offsetting the costs of CO2 capture at the power plant. In California, Kern County contains the largest oil reservoirs and produces 76% of California's oil. Most of the production at depths suitable for CCS combined with CO2 EOR comes from three reservoirs: the Vedder and Temblor formations and the Stevens Sandstone of the Monterey Formation. These formations were evaluated for GCS and CO2 EOR potential at the North and South Coles Levee (Stevens Sandstone), Greeley (Vedder) and McKittrick (Temblor) fields. CO2 EOR could be expected to produce an additional 150 million bbls of oil. The total storage space created by pre- and post-EOR fluid production for all three reservoirs is approximately 104 million metric tons (MMT). Large fixed sources in California produce 156 MMT/yr of CO2, and sources in Kern County produce 26 MMT/yr (WESTCARB, 2012). Therefore, the fields could store about four years of local large fixed source emissions and about two thirds of statewide emissions. However, from a global perspective, burning the additional oil produced by CO2 EOR would generate an additional 65 MMT of CO2 if not captured. This would result in a net reduction of greenhouse gas of only 39 MMT rather than the full 104 MMT. If the water produced along with the oil recovered during CO2 EOR operations is not reinjected into the reservoir, the storage space could be much higher.

  17. Fitting a Structured Juvenile-Adult Model for Green Tree Frogs to Population Estimates from Capture-Mark-Recapture Field Data

    USGS Publications Warehouse

    Ackleh, A.S.; Carter, J.; Deng, K.; Huang, Q.; Pal, N.; Yang, X.

    2012-01-01

    We derive point and interval estimates for an urban population of green tree frogs (Hyla cinerea) from capture-mark-recapture field data obtained during the years 2006-2009. We present an infinite-dimensional least-squares approach which compares a mathematical population model to the statistical population estimates obtained from the field data. The model is composed of nonlinear first-order hyperbolic equations describing the dynamics of the amphibian population where individuals are divided into juveniles (tadpoles) and adults (frogs). To solve the least-squares problem, an explicit finite difference approximation is developed. Convergence results for the computed parameters are presented. Parameter estimates for the vital rates of juveniles and adults are obtained, and standard deviations for these estimates are computed. Numerical results for the model sensitivity with respect to these parameters are given. Finally, the above-mentioned parameter estimates are used to illustrate the long-time behavior of the population under investigation. ?? 2011 Society for Mathematical Biology.

  18. Seven-Step Framework for Critical Analysis and Its Application in the Field of Physical Therapy.

    PubMed

    Nixon, Stephanie A; Yeung, Euson; Shaw, James A; Kuper, Ayelet; Gibson, Barbara E

    2016-09-29

    Critical analysis (or the ability to recognize taken-for-granted assumptions and their effects) is a skill that requires teaching and practice. The purpose of this article is to introduce a framework for critically analyzing assumptions within physical therapy and illustrate its utility through application to 2 examples: a physical therapy clinic logo and an outcome measure for health-related quality of life (HRQOL). This 7-step framework for critical analysis was created for a pilot project to develop reflexivity among senior physical therapist students and further developed through an iterative process of reflecting on its utility for advancing the field of physical therapy. The 7-step framework is an iterative process involving a cascade of 7 steps: (1) name the specific aspect of practice being analyzed, (2) identify the intended purposes of this aspect of practice, (3) uncover the assumptions that support these intended purposes, (4) identify who benefits, (5) identify who is disadvantaged, (6) link these specific ideas to society-level patterns, and (7) conceive of alternatives that mitigate actual or potential harms. It is emphasized that being theoretically critical does not equate to being negative. Rather, the word "critical" is used in the sense of thinking deeply and carefully about the intended and unintended consequences of actions (including common professional practices, ways of speaking, and visual representations) in order to reflect on and mature the field of physical therapy. The purpose of critical analysis is to invite and promote dialogue that assists physical therapist clinicians, researchers, and students to arrive at new insights about the impacts of their day-to-day actions.

  19. Conceptual design of a nonscaling fixed field alternating gradient accelerator for protons and carbon ions for charged particle therapy

    NASA Astrophysics Data System (ADS)

    Peach, K. J.; Aslaninejad, M.; Barlow, R. J.; Beard, C. D.; Bliss, N.; Cobb, J. H.; Easton, M. J.; Edgecock, T. R.; Fenning, R.; Gardner, I. S. K.; Hill, M. A.; Owen, H. L.; Johnstone, C. J.; Jones, B.; Jones, T.; Kelliher, D. J.; Khan, A.; Machida, S.; McIntosh, P. A.; Pattalwar, S.; Pasternak, J.; Pozimski, J.; Prior, C. R.; Rochford, J.; Rogers, C. T.; Seviour, R.; Sheehy, S. L.; Smith, S. L.; Strachan, J.; Tygier, S.; Vojnovic, B.; Wilson, P.; Witte, H.; Yokoi, T.

    2013-03-01

    The conceptual design for a nonscaling fixed field alternating gradient accelerator suitable for charged particle therapy (the use of protons and other light ions to treat some forms of cancer) is described.

  20. Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina

    SciTech Connect

    Farías, R. O.; Trivillin, V. A.; Portu, A. M.; Schwint, A. E.; González, S. J.; Garabalino, M. A.; Monti Hughes, A.; Pozzi, E. C. C.; Thorp, S. I.; Curotto, P.; Miller, M. E.; Santa Cruz, G. A.; Saint Martin, G.; Ferraris, S.; Santa María, J.; Rovati, O.; Lange, F.; Bortolussi, S.; Altieri, S.

    2015-07-15

    Purpose: Many types of lung tumors have a very poor prognosis due to their spread in the whole organ volume. The fact that boron neutron capture therapy (BNCT) would allow for selective targeting of all the nodules regardless of their position, prompted a preclinical feasibility study of ex situ BNCT at the thermal neutron facility of RA-3 reactor in the province of Buenos Aires, Argentina. (L)-4p-dihydroxy-borylphenylalanine fructose complex (BPA-F) biodistribution studies in an adult sheep model and computational dosimetry for a human explanted lung were performed to evaluate the feasibility and the therapeutic potential of ex situ BNCT. Methods: Two kinds of boron biodistribution studies were carried out in the healthy sheep: a set of pharmacokinetic studies without lung excision, and a set that consisted of evaluation of boron concentration in the explanted and perfused lung. In order to assess the feasibility of the clinical application of ex situ BNCT at RA-3, a case of multiple lung metastases was analyzed. A detailed computational representation of the geometry of the lung was built based on a real collapsed human lung. Dosimetric calculations and dose limiting considerations were based on the experimental results from the adult sheep, and on the most suitable information published in the literature. In addition, a workable treatment plan was considered to assess the clinical application in a realistic scenario. Results: Concentration-time profiles for the normal sheep showed that the boron kinetics in blood, lung, and skin would adequately represent the boron behavior and absolute uptake expected in human tissues. Results strongly suggest that the distribution of the boron compound is spatially homogeneous in the lung. A constant lung-to-blood ratio of 1.3 ± 0.1 was observed from 80 min after the end of BPA-F infusion. The fact that this ratio remains constant during time would allow the blood boron concentration to be used as a surrogate and indirect

  1. Effect of field experiences on music therapy students' perceptions of choral music for geriatric wellness programs.

    PubMed

    Vanweelden, Kimberly; Whipple, Jennifer

    2004-01-01

    The purpose of the study was to examine the effect of field experiences on music therapy students' perceptions of choral music for geriatric wellness programs. Specifically, the study investigated music therapy students': a) personal comfort working with senior adult singers; b) perceptions of preparation in their educational training to work with senior adults in a choral music wellness program; c) perceptions of senior adults' functioning levels as singers in choral ensembles; d) perceptions of senior adults' functioning levels as learners; and e) willingness to seek additional opportunities to lead senior adults in choral music wellness programs. Comparative analysis using pretest and posttest scores for each grouping was completed. Significant mean score differences were found in the categories of student comfort, preparation, perceptions of singing, and willingness, with gains from pre- to posttest in all categories. The general demographics and perceptions of learning groupings increased and decreased, respectively, though not significantly, following the field experience. Analysis combining all groups, creating an overall pretest and posttest score, was also completed. Results revealed that students felt significantly more positive about choral music being used in wellness programs for senior adults after the field experience.

  2. Gene therapy for hemoglobinopathies: the state of the field and the future.

    PubMed

    Chandrakasan, Shanmuganathan; Malik, Punam

    2014-04-01

    After nearly two decades of struggle, gene therapy for hemoglobinopathies using vectors carrying β or γ-globin gene has finally reached the clinical doorsteps. This was made possible by advances made in our understanding of critical regulatory elements required for high level of globin gene expression and improved gene transfer vectors and methodologies. Development of gene editing technologies and reprogramming somatic cells for regenerative medicine holds the promise of genetic correction of hemoglobinopathies in the future. This article will review the state of the field and the upcoming technologies that will allow genetic therapeutic correction of hemoglobinopathies.

  3. Optimizing field patching in passively scattered proton therapy with the use of beam current modulation.

    PubMed

    Hill, Patrick M; Klein, Eric E; Bloch, Charles

    2013-08-21

    Treatment plans for patched-field proton therapy may not be clinically acceptable due to the dose heterogeneity introduced in the target when combining the dose distributions from two separate fields. MCNPX simulations were performed for various configurations of the Mevion S250 beamline to determine spread-out Bragg peak dose distributions and patched-field treatment plans delivered using a rotating modulator wheel to depths in the clinically relevant range between 5.0 and 30.0 cm. The dose non-uniformity (DNU) metric was defined as the difference between the maximum and minimum dose relative to the prescription observed in a patched dose distribution. The DNU was first evaluated for dose distributions from a standard delivery using constant beam current and combining through-field lateral dose profiles and with patch-field distal dose profiles. Patch-field distal dose profiles were then optimized using beam current modulation in an attempt to better complement the through-field lateral dose profiles when combined into a patched dose distribution. Using standard deliveries, DNU was 10% or less only when patching lateral profiles 12.5-17.5 cm deep. Significantly greater DNU was observed for patches outside of this range, at times exceeding 35%. Using optimized distal profiles, DNU was reduced to 10% or less for all lateral profiles deeper than 15.0 cm. Optimizing beam current modulation was found to create distal profiles with more gradual dose falloff than found in a standard delivery, allowing optimized distal dose distributions to sum more homogeneously with lateral dose distributions. The hot or cold spots that often appear in patched dose distributions from standard deliveries may therefore be mitigated by optimizing beam current. This method may also be applied to systems other than the Mevion system to further improve patched-field dose homogeneity.

  4. Capturing Heaven

    NASA Astrophysics Data System (ADS)

    Martin, G.

    2009-02-01

    Science communication, like other areas of study, features prominent figures who lead the field. One such individual is Jean-Pierre Luminet, a researcher, communicator, artist and author. As recipient of the 2007 European Science Communication Prize for Communicator of the Year, Jean-Pierre is at the forefront of his field. The CAPjournal editorial team interviewed Jean-Pierre to discover more about the man, his mission and his methods.

  5. Estimating Population Size for Capercaillie (Tetrao urogallus L.) with Spatial Capture-Recapture Models Based on Genotypes from One Field Sample

    PubMed Central

    Mollet, Pierre; Kéry, Marc; Gardner, Beth; Pasinelli, Gilberto; Royle, J. Andrew

    2015-01-01

    We conducted a survey of an endangered and cryptic forest grouse, the capercaillie Tetrao urogallus, based on droppings collected on two sampling occasions in eight forest fragments in central Switzerland in early spring 2009. We used genetic analyses to sex and individually identify birds. We estimated sex-dependent detection probabilities and population size using a modern spatial capture-recapture (SCR) model for the data from pooled surveys. A total of 127 capercaillie genotypes were identified (77 males, 46 females, and 4 of unknown sex). The SCR model yielded atotal population size estimate (posterior mean) of 137.3 capercaillies (posterior sd 4.2, 95% CRI 130–147). The observed sex ratio was skewed towards males (0.63). The posterior mean of the sex ratio under the SCR model was 0.58 (posterior sd 0.02, 95% CRI 0.54–0.61), suggesting a male-biased sex ratio in our study area. A subsampling simulation study indicated that a reduced sampling effort representing 75% of the actual detections would still yield practically acceptable estimates of total size and sex ratio in our population. Hence, field work and financial effort could be reduced without compromising accuracy when the SCR model is used to estimate key population parameters of cryptic species. PMID:26087321

  6. Estimating population size for Capercaillie (Tetrao urogallus L.) with spatial capture-recapture models based on genotypes from one field sample

    USGS Publications Warehouse

    Mollet, Pierre; Kery, Marc; Gardner, Beth; Pasinelli, Gilberto; Royle, Andy

    2015-01-01

    We conducted a survey of an endangered and cryptic forest grouse, the capercaillie Tetrao urogallus, based on droppings collected on two sampling occasions in eight forest fragments in central Switzerland in early spring 2009. We used genetic analyses to sex and individually identify birds. We estimated sex-dependent detection probabilities and population size using a modern spatial capture-recapture (SCR) model for the data from pooled surveys. A total of 127 capercaillie genotypes were identified (77 males, 46 females, and 4 of unknown sex). The SCR model yielded atotal population size estimate (posterior mean) of 137.3 capercaillies (posterior sd 4.2, 95% CRI 130–147). The observed sex ratio was skewed towards males (0.63). The posterior mean of the sex ratio under the SCR model was 0.58 (posterior sd 0.02, 95% CRI 0.54–0.61), suggesting a male-biased sex ratio in our study area. A subsampling simulation study indicated that a reduced sampling effort representing 75% of the actual detections would still yield practically acceptable estimates of total size and sex ratio in our population. Hence, field work and financial effort could be reduced without compromising accuracy when the SCR model is used to estimate key population parameters of cryptic species.

  7. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage

    PubMed Central

    Artati, Anna; Adamski, Jerzy

    2016-01-01

    Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF) to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease. PMID:27959944

  8. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

    PubMed

    Storch, Katja; Dickreuter, Ellen; Artati, Anna; Adamski, Jerzy; Cordes, Nils

    2016-01-01

    Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF) to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

  9. Optimal simulations of ultrasonic fields produced by large thermal therapy arrays using the angular spectrum approach.

    PubMed

    Zeng, Xiaozheng; McGough, Robert J

    2009-05-01

    The angular spectrum approach is evaluated for the simulation of focused ultrasound fields produced by large thermal therapy arrays. For an input pressure or normal particle velocity distribution in a plane, the angular spectrum approach rapidly computes the output pressure field in a three dimensional volume. To determine the optimal combination of simulation parameters for angular spectrum calculations, the effect of the size, location, and the numerical accuracy of the input plane on the computed output pressure is evaluated. Simulation results demonstrate that angular spectrum calculations performed with an input pressure plane are more accurate than calculations with an input velocity plane. Results also indicate that when the input pressure plane is slightly larger than the array aperture and is located approximately one wavelength from the array, angular spectrum simulations have very small numerical errors for two dimensional planar arrays. Furthermore, the root mean squared error from angular spectrum simulations asymptotically approaches a nonzero lower limit as the error in the input plane decreases. Overall, the angular spectrum approach is an accurate and robust method for thermal therapy simulations of large ultrasound phased arrays when the input pressure plane is computed with the fast nearfield method and an optimal combination of input parameters.

  10. ALS Biomarkers for Therapy Development: State of the Field & Future Directions

    PubMed Central

    Benatar, Michael; Boylan, Kevin; Jeromin, Andreas; Rutkove, Seward B.; Berry, James; Atassi, Nazem; Bruijn, Lucie

    2015-01-01

    Biomarkers have become the focus of intense research in the field of amyotrophic lateral sclerosis (ALS), with the hope that they might aid therapy development efforts. Notwithstanding the discovery of many candidate biomarkers, none have yet emerged as validated tools for drug development. In this review we present a nuanced view of biomarkers based on the perspective of the FDA; highlight the distinction between discovery and validation; describe existing and emerging resources; review leading biological fluid-based, electrophysiological and neuroimaging candidates relevant to therapy development efforts; discuss lessons learned from biomarker initiatives in related neurodegenerative diseases; and outline specific steps that we, as a field, might take in order to hasten the development and validation of biomarkers that will prove useful in enhancing efforts to develop effective treatments for ALS patients. Most important among these perhaps is the proposal to establish a federated ALS Biomarker Consortium (ABC) in which all interested and willing stakeholders may participate with equal opportunity to contribute to the broader mission of biomarker development and validation. PMID:26574709

  11. Low-level laser therapy on bone repair: is there any effect outside the irradiated field?

    PubMed

    Batista, Jonas Dantas; Sargenti-Neto, Sérgio; Dechichi, Paula; Rocha, Flaviana Soares; Pagnoncelli, Rogério Miranda

    2015-07-01

    The biological effects of local therapy with laser on bone repair have been well demonstrated; however, this possible effect on bone repair outside the irradiated field has not been evaluated. The aim of this study was to investigate the effect of low-level laser therapy (LLLT) (λ = 830 nm) on repair of surgical bone defects outside the irradiated field, in rats. Sixty Wistar rats were submitted to osteotomy on the left femur and randomly separated into four groups (n = 15): group I, control, bone defect only; group II, laser applied on the right femur (distant dose); group III, laser applied locally on the bone defect and also on the right femur (local and distant doses); and group IV, laser applied locally on the left femur (local dose). Laser groups received applications within a 48-h interval in one point per session of density energy (DE) = 210 J/cm(2), P = 50 mW, t = 120 s, and beam diameter of 0.028 cm. Five animals of each group were euthanized 7, 15, and 21 days after surgery. Histologic analysis in all groups showed new bone formation in the region of interest (ROI) at 7 days. After 15 days, bone remodeling with a decrease of bone neoformation in the marrow area was observed in all groups. After 21 days, advanced bone remodeling with new bone mostly located in the cortical area was observed. The histomorphometric analysis showed at 7 days a significant increase of bone formation in groups III and IV compared to groups I and II. At days 15 and 21, histomorphometric analysis showed no significant differences between them. Laser therapy presented a positive local biostimulative effect in the early stage of bone healing, but the LLLT effect was not observed a long distance from the evaluated area.

  12. Electric field characteristics of electroconvulsive therapy with individualized current amplitude: a preclinical study.

    PubMed

    Lee, Won Hee; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

    2013-01-01

    This study examines the characteristics of the electric field induced in the brain by electroconvulsive therapy (ECT) with individualized current amplitude. The electric field induced by bilateral (BL), bifrontal (BF), right unilateral (RUL), and frontomedial (FM) ECT electrode configurations was computed in anatomically realistic finite element models of four nonhuman primates (NHPs). We generated maps of the electric field strength relative to an empirical neural activation threshold, and determined the stimulation strength and focality at fixed current amplitude and at individualized current amplitudes corresponding to seizure threshold (ST) measured in the anesthetized NHPs. The results show less variation in brain volume stimulated above threshold with individualized current amplitudes (16-36%) compared to fixed current amplitude (30-62%). Further, the stimulated brain volume at amplitude-titrated ST is substantially lower than that for ECT with conventional fixed current amplitudes. Thus individualizing the ECT stimulus current could compensate for individual anatomical variability and result in more focal and uniform electric field exposure across different subjects compared to the standard clinical practice of using high, fixed current for all patients.

  13. Capturing Callisto

    NASA Technical Reports Server (NTRS)

    2007-01-01

    The New Horizons Long Range Reconnaissance Imager (LORRI) captured these two images of Jupiter's outermost large moon, Callisto, as the spacecraft flew past Jupiter in late February. New Horizons' closest approach distance to Jupiter was 2.3 million kilometers (1.4 million miles), not far outside Callisto's orbit, which has a radius of 1.9 million kilometers (1.2 million miles). However, Callisto happened to be on the opposite side of Jupiter during the spacecraft's pass through the Jupiter system, so these images, taken from 4.7 million kilometers (3.0 million miles) and 4.2 million kilometers (2.6 million miles) away, are the closest of Callisto that New Horizons obtained.

    Callisto's ancient, crater-scarred surface makes it very different from its three more active sibling satellites, Io, Europa and Ganymede. Callisto, 4,800 kilometers (3000 miles) in diameter, displays no large-scale geological features other than impact craters, and every bright spot in these images is a crater. The largest impact feature on Callisto, the huge basin Valhalla, is visible as a bright patch at the 10 o'clock position. The craters are bright because they have excavated material relatively rich in water ice from beneath the dark, dusty material that coats most of the surface.

    The two images show essentially the same side of Callisto -- the side that faces Jupiter -- under different illumination conditions. The images accompanied scans of Callisto's infrared spectrum with New Horizons' Linear Etalon Imaging Spectral Array (LEISA). The New Horizons science team designed these scans to study how the infrared spectrum of Callisto's water ice changes as lighting and viewing conditions change, and as the ice cools through Callisto's late afternoon. The infrared spectrum of water ice depends slightly on its temperature, and a goal of New Horizons when it reaches the Pluto system (in 2015) is to use the water ice features in the spectrum of Pluto's moon Charon, and

  14. Effect of organ size and position on out-of-field dose distributions during radiation therapy

    NASA Astrophysics Data System (ADS)

    Scarboro, Sarah B.; Stovall, Marilyn; White, Allen; Smith, Susan A.; Yaldo, Derek; Kry, Stephen F.; Howell, Rebecca M.

    2010-12-01

    Mantle field irradiation has historically been the standard radiation treatment for Hodgkin lymphoma. It involves treating large regions of the chest and neck with high doses of radiation (up to 30 Gy). Previous epidemiological studies on the incidence of second malignancies following radiation therapy for Hodgkin lymphoma have revealed an increased incidence of second tumors in various organs, including lung, breast, thyroid and digestive tract. Multiple other studies, including the Surveillance, Epidemiology and End Results, indicated an increased incidence in digestive tract including stomach cancers following mantle field radiotherapy. Assessment of stomach dose is challenging because the stomach is outside the treatment field but very near the treatment border where there are steep dose gradients. In addition, the stomach can vary greatly in size and position. We sought to evaluate the dosimetric impact of the size and variable position of the stomach relative to the field border for a typical Hodgkin lymphoma mantle field irradiation. The mean stomach dose was measured using thermoluminescent dosimetry for nine variations in stomach size and position. The mean doses to the nine stomach variations ranged from 0.43 to 0.83 Gy when 30 Gy was delivered to the treatment isocenter. Statistical analyses indicated that there were no significant differences in the mean stomach dose when the stomach was symmetrically expanded up to 3 cm or shifted laterally (medial, anterior or posterior shifts) by up to 3 cm. There was, however, a significant (P > 0.01) difference in the mean dose when the stomach was shifted superiorly or inferiorly by >=2.5 cm.

  15. Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

    SciTech Connect

    Beadle, Beth M.; Guadagnolo, B. Ashleigh Ballo, Matthew T.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Cormier, Janice N.; Mansfield, Paul F.; Ross, Merrick I.; Zagars, Gunar K.

    2009-04-01

    Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) had sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.

  16. Acoustic field characterization of the Duolith: Measurements and modeling of a clinical shock wave therapy device

    PubMed Central

    Perez, Camilo; Chen, Hong; Matula, Thomas J.; Karzova, Maria; Khokhlova, Vera A.

    2013-01-01

    Extracorporeal shock wave therapy (ESWT) uses acoustic pulses to treat certain musculoskeletal disorders. In this paper the acoustic field of a clinical portable ESWT device (Duolith SD1) was characterized. Field mapping was performed in water for two different standoffs of the electromagnetic head (15 or 30 mm) using a fiber optic probe hydrophone. Peak positive pressures at the focus ranged from 2 to 45 MPa, while peak negative pressures ranged from −2 to −11 MPa. Pulse rise times ranged from 8 to 500 ns; shock formation did not occur for any machine settings. The maximum standard deviation in peak pressure at the focus was 1.2%, indicating that the Duolith SD1 generates stable pulses. The results compare qualitatively, but not quantitatively with manufacturer specifications. Simulations were carried out for the short standoff by matching a Khokhlov-Zabolotskaya-Kuznetzov equation to the measured field at a plane near the source, and then propagating the wave outward. The results of modeling agree well with experimental data. The model was used to analyze the spatial structure of the peak pressures. Predictions from the model suggest that a true shock wave could be obtained in water if the initial pressure output of the device were doubled. PMID:23927207

  17. Normal-conducting scaling fixed field alternating gradient accelerator for proton therapy

    NASA Astrophysics Data System (ADS)

    Garland, J. M.; Appleby, R. B.; Owen, H.; Tygier, S.

    2015-09-01

    In this paper we present a new lattice design for a 30-350 MeV scaling fixed-field alternating gradient accelerator for proton therapy and tomography—NORMA (NOrmal-conducting Racetrack Medical Accelerator). The energy range allows the realization of proton computed tomography and utilizes normal conducting magnets in both a conventional circular ring option and a novel racetrack configuration, both designed using advanced optimization algorithms we have developed in pyzgoubi. Both configurations consist of ten focusing-defocusing-focusing triplet cells and operate in the second stability region of Hills equation. The ring configuration has a circumference of 60 m, a peak magnetic field seen by the beam of <1.6 T , a maximum horizontal orbit excursion of 44 cm and a dynamic aperture of 68 mm mrad—determined using a novel dynamic aperture (DA) calculation technique. The racetrack alternative is realized by adding magnet-free drift space in between cells at two opposing points in the ring, to facilitate injection and extraction. Our racetrack design has a total magnet-free straight lengths of 4.9 m, a circumference of 71 m, a peak magnetic field seen by the beam of <1.74 T , a maximum horizontal orbit excursion of 50 cm and a DA of 58 mm mrad. A transverse magnet misalignment model is also presented for the ring and racetrack configurations where the DA remains above 40 mm mrad for randomly misaligned error distributions with a standard deviation up to 100 μ m .

  18. Static Magnetic Field Therapy for Carpal Tunnel Syndrome: A Feasibility Study

    PubMed Central

    Colbert, Agatha P.; Markov, Marko S.; Carlson, Nels; Gregory, William L.; Carlson, Hans; Elmer, Patricia J.

    2010-01-01

    Objectives To assess the feasibility of conducting trials of static magnetic field (SMF) therapy for carpal tunnel syndrome (CTS), to collect preliminary data on the effectiveness of two SMF dosages and to explore the influence of a SMF on median nerve conduction. Design Randomized, double blind, sham controlled trial with 6-week intervention and 12-week follow-up. Setting University hospital outpatient clinics Participants Women and men (N=60), ages 21–65, with electrophysiologically-confirmed CTS diagnosis, recruited from the general population. Interventions Participants wore nightly either neodymium magnets that delivered either 15 or 45mTesla (mT) to the contents of the carpal canal, or a non-magnetic disk. Main Outcome Measures Symptom Severity Scale (SSS) and Function Severity Scale (FSS) of the Boston Carpal Tunnel Questionnaire (BCTQ) and 4 median nerve parameters: sensory distal latency, sensory nerve action potential amplitude, motor distal latency and compound motor action potential amplitude). Results 58 of 60 randomized participants completed the study. There were no significant between-group differences for change in the primary endpoint SSS or for FSS or median nerve conduction parameters. For the SSS and the FSS each group showed a reduction at 6-weeks indicating improvement in symptoms. Conclusions This study demonstrated the feasibility and safety of testing SMF therapy for CTS. There were no between-group differences observed for the BCTQ or median nerve parameters following 6 weeks of SMF therapy. Significant within-group, symptomatic improvements of the same magnitude were experienced by participants in both active and sham magnet groups. Future studies are needed to optimize SMF dosimetry and resolve issues related to the use of sham controls in SMF trials. PMID:20599049

  19. Tumor treating field therapy in combination with bevacizumab for the treatment of recurrent glioblastoma.

    PubMed

    Omar, Ayman I

    2014-10-27

    A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA approved in April 2011 for the treatment of patients 22 years or older with rGBM. The device delivers alternating electric fields and is programmed to ensure maximal tumor cell kill. Glioblastoma is the most common type of glioma and has an estimated incidence of approximately 10,000 new cases per year in the United States alone. This tumor is particularly resistant to treatment and is uniformly fatal especially in the recurrent setting. Prior to the approval of the TTF System, the only FDA approved treatment for rGBM was bevacizumab. Bevacizumab is a humanized monoclonal antibody targeted against the vascular endothelial growth factor (VEGF) protein that drives tumor angiogenesis. By blocking the VEGF pathway, bevacizumab can result in a significant radiographic response (pseudoresponse), improve progression free survival and reduce corticosteroid requirements in rGBM patients. Bevacizumab however failed to prolong overall survival in a recent phase III trial. A pivotal phase III trial (EF-11) demonstrated comparable overall survival between physicians' choice chemotherapy and TTF Therapy but better quality of life were observed in the TTF arm. There is currently an unmet need to develop novel approaches designed to prolong overall survival and/or improve quality of life in this unfortunate patient population. One appealing approach would be to combine the two currently approved treatment modalities namely bevacizumab and TTF Therapy. These two treatments are currently approved as monotherapy, but their combination has never been evaluated in a clinical trial. We have developed an approach for combining those two treatment modalities and treated 2 rGBM patients. Here we describe a detailed methodology outlining this novel treatment protocol and present representative data from one of the treated patients.

  20. Intensity modulated radiation therapy with field rotation--a time-varying fractionation study.

    PubMed

    Dink, Delal; Langer, Mark P; Rardin, Ronald L; Pekny, Joseph F; Reklaitis, Gintaras V; Saka, Behlul

    2012-06-01

    This paper proposes a novel mathematical approach to the beam selection problem in intensity modulated radiation therapy (IMRT) planning. The approach allows more beams to be used over the course of therapy while limiting the number of beams required in any one session. In the proposed field rotation method, several sets of beams are interchanged throughout the treatment to allow a wider selection of beam angles than would be possible with fixed beam orientations. The choice of beamlet intensities and the number of identical fractions for each set are determined by a mixed integer linear program that controls jointly for the distribution per fraction and the cumulative dose distribution delivered to targets and critical structures. Trials showed the method allowed substantial increases in the dose objective and/or sparing of normal tissues while maintaining cumulative and fraction size limits. Trials for a head and neck site showed gains of 25%-35% in the objective (average tumor dose) and for a thoracic site gains were 7%-13%, depending on how strict the fraction size limits were set. The objective did not rise for a prostate site significantly, but the tolerance limits on normal tissues could be strengthened with the use of multiple beam sets.

  1. Exosomes and the emerging field of exosome-based gene therapy.

    PubMed

    O'Loughlin, Aisling J; Woffindale, Caroline A; Wood, Matthew J A

    2012-08-01

    Exosomes are a subtype of membrane vesicle released from the endocytic compartment of live cells. They play an important role in endogenous cell-to-cell communication. Previously shown to be capable of traversing biological barriers and to naturally transport functional nucleic acids between cells, they potentially represent a novel and exciting drug delivery vehicle for the field of gene therapy. Existing delivery vehicles are limited by concerns regarding their safety, toxicity and efficacy. In contrast, exosomes, as a natural cell-derived nanocarrier, are immunologically inert if purified from a compatible cell source and possess an intrinsic ability to cross biological barriers. Already utilised in a number of clinical trials, exosomes appear to be well-tolerated, even following repeat administration. Recent studies have shown that exosomes may be used to encapsulate and protect exogenous oligonucleotides for delivery to target cells. They therefore may be valuable for the delivery of RNA interference and microRNA regulatory molecules in addition to other single-stranded oligonucleotides. Prior to clinical translation, this nanotechnology requires further development by refinement of isolation, purification, loading, delivery and targeting protocols. Thus, exosome-mediated nanodelivery is highly promising and may fill the void left by current delivery methods for systemic gene therapy.

  2. [Studies on hormone-polymer composites in urological field--their application in prostatic cancer therapy].

    PubMed

    Yamanaka, H

    1983-12-01

    Our studies on the application of hormone-polymer composites in urological field are discussed in this review. We first studied the modes of in vivo and in vitro release of testosterone from vinyl polymer-testosterone composites prepared by radiation-induced polymerization. It was ascertained by our group that in vivo and in vitro release of testosterone from biodegradable copolypeptide -testosterone composites as well as vinyl polymer composites was well controlled. Using this system, we were successful in preparing a testicular prosthesis, which was made of vinyl polymer-testosterone composites and was ascertained to release testosterone constantly for a long period in the dose range of clinical usage. We also applied this sustained release drug delivery system to the method of administration of an LH x RH agonist, which was one of the best therapeutic drugs for androgen dependent prostatic cancer. Sustained release of the LH x RH agonist in the dose range of clinical usage over a period of several months from copolymer-LH x RH agonist composites was confirmed in both male rats and in prostatic cancer patients. Prostatic cancer cells contain a major secretion protein (alpha-protein or estramustine-binding protein) and estramustine has a high affinity for alpha-protein. Therefore, we examined the effect of an estramustine-microsphere containing anticancer drugs, namely, the missile therapy for prostatic cancer. The missile therapy should open the way to specific and selective chemotherapy for prostatic cancer.

  3. Magnetic field activated drug release system based on magnetic PLGA microspheres for chemo-thermal therapy.

    PubMed

    Fang, Kun; Song, Lina; Gu, Zhuxiao; Yang, Fang; Zhang, Yu; Gu, Ning

    2015-12-01

    Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3 wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30 min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.

  4. Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Hu, Yue; Yang, Yamin; Wang, Hongjun; Du, Henry

    2013-02-01

    Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

  5. Brief trauma intervention with Rwandan genocide-survivors using thought field therapy.

    PubMed

    Connolly, Suzanne; Sakai, Caroline

    2011-01-01

    This randomized waitlist control study examined the efficacy of Thought Field Therapy (TFT) in reducing Posttraumatic Stress Disorder symptoms in survivors of the 1994 genocide in Rwanda. Participants included 145 adult genocide survivors randomly assigned to an immediate TFT treatment group or a waitlist control group. Group differences adjusted for pretest scores and repeated measures anovas were statistically significant at p < .001 for 9 of 10 TSI trauma subscales and for both severity and frequency on the MPSS, with moderate to large effect sizes. Reduced trauma symptoms for the group receiving TFT were found for all scales. Reductions in trauma symptoms were sustained at a 2-year follow-up assessment. Limitations, clinical implications, and future research are discussed.

  6. L-Phenylalanine preloading reduces the (10)B(n, α)(7)Li dose to the normal brain by inhibiting the uptake of boronophenylalanine in boron neutron capture therapy for brain tumours.

    PubMed

    Watanabe, Tsubasa; Tanaka, Hiroki; Fukutani, Satoshi; Suzuki, Minoru; Hiraoka, Masahiro; Ono, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. Previously, high doses of one of the boron compounds used for BNCT, L-BPA, were found to reduce the boron-derived irradiation dose to the central nervous system. However, injection with a high dose of L-BPA is not feasible in clinical settings. We aimed to find an alternative method to improve the therapeutic efficacy of this therapy. We examined the effects of oral preloading with various analogues of L-BPA in a xenograft tumour model and found that high-dose L-phenylalanine reduced the accumulation of L-BPA in the normal brain relative to tumour tissue. As a result, the maximum irradiation dose in the normal brain was 19.2% lower in the L-phenylalanine group relative to the control group. This study provides a simple strategy to improve the therapeutic efficacy of conventional boron compounds for BNCT for brain tumours and the possibility to widen the indication of BNCT to various kinds of other tumours.

  7. Dosimetric effects on small-field beam-modeling for stereotactic body radiation therapy

    NASA Astrophysics Data System (ADS)

    Cho, Woong; Kim, Suzy; Kim, Jung-In; Wu, Hong-Gyun; Jung, Joo-Young; Kim, Min-Joo; Suh, Tae-Suk; Kim, Jin-Young; Kim, Jong Won

    2015-02-01

    The treatment planning of stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) requires high accuracy of dosimetric data for small radiation fields. The dosimetric effects on the beam-modeling process of a treatment planning system (TPS) were investigated using different measured small-field data sets. We performed small-field dosimetry with three detectors: a CC13 ion chamber, a CC01 ion chamber, and an edge detector. Percentage depth doses (PDDs) and dose profiles for field sizes given by 3 × 3 cm2, 2 × 2 cm2, and 1 × 1 cm2 were obtained for 6 MV and 15 MV photon beams. Each measured data set was used as data input for a TPS, in which a beam-modeling process was implemented using the collapsed cone convolution (CCC) algorithm for dose calculation. The measured data were used to generate six beam-models based on each combination of detector type and photon energy, which were then used to calculate the corresponding PDDs and dose profiles for various depths and field sizes. Root mean square differences (RMSDs) between the calculated and the measured doses were evaluated for the PDDs and the dose profiles. The RMSDs of PDDs beyond the maximum dose depth were within an accuracy of 0.2-0.6%, being clinically acceptable. The RMSDs of the dose profiles corresponding to the CC13, the CC01, and the edge detector were 2.80%, 1.49%, and 1.46% for a beam energy of 6 MV and 2.34%, 1.15%, and 1.44% for a beam energy of 15 MV, respectively. The calculated results for the CC13 ion chamber showed the most discrepancy compared to the measured data, due to the relatively large sensitive volume of this detector. However, the calculated dose profiles for the detectors were not significantly different from another. The physical algorithm used in the beam-modeling process did not seem to be sensitive to blurred data measured with detectors with large sensitive volumes. Each beam-model was used to clinically evaluate lung and lymphatic node SBRT plans

  8. Pulsed radiofrequency electromagnetic field therapy: a potential novel treatment of plantar fasciitis.

    PubMed

    Brook, Joel; Dauphinee, Damien M; Korpinen, Jaryl; Rawe, Ian M

    2012-01-01

    Plantar fasciitis is a common cause of heel pain, and although treatments are usually conservative, they can take up to 2 years to achieve resolution. A double-blind, multicenter, randomized, placebo-controlled study was used to evaluate a small, wearable, extended-use pulsed radiofrequency electromagnetic field (PRFE) device as a treatment of plantar fasciitis. A total of 70 subjects diagnosed with plantar fasciitis were enrolled in the present study. The subjects were randomly assigned a placebo or active PRFE device. The subjects were instructed to wear the PRFE device overnight, record their morning and evening pain using a 0- to 10-point visual analog scale (VAS), and log any medication use. The primary outcome measure for the present study was morning pain, a hallmark of plantar fasciitis. The study group using the active PRFE device showed progressive decline in morning pain. The day 7 AM-VAS score was 40% lower than the day 1 AM-VAS score. The control group, in comparison, showed a 7% decline. A significantly different decline was demonstrated between the 2 groups (p = .03). The PM-VAS scores declined by 30% in the study group and 19% in the control group, although the difference was not significant. Medication use in the study group also showed a trend downward, but the use in the control group remained consistent with the day 1 levels. PRFE therapy worn on a nightly basis appears to offer a simple, drug-free, noninvasive therapy to reduce the pain associated with plantar fasciitis.

  9. The effects of ionizing radiation and dexamethasone on the blood-brain-barrier (BBB) and blood-tumor-barrier (BTB): Implications for boron neutron capture therapy (BNCT) of brain tumors

    SciTech Connect

    Dorn, R.V. III; Spickard, J.H.; Griebenow, M.L.

    1988-01-01

    Currently envisioned techniques for Boron Neutron Capture Therapy (BNCT) of brain tumors rely on the increased permeability of the blood-brain-barrier (BBB) (more specifically, the blood-tumor-barrier (BTB)) which occurs around the malignant tumor. As a result of this increased permeability, higher boron concentrations (Na/sub 2/B/sub 12/H/sub 11/SH) should be obtainable in the tumor than in the surrounding normal brain. The effects on the BBB and BTB by the ionizing component of this radiation and by the steroid dexamethasone (almost universally used in the clinical management of these patients) must be considered in the formulation of this treatment technique. 32 refs., 5 tabs.

  10. Music Therapy as a Caring Intervention: Swedish Musicians Learning a New Professional Field

    ERIC Educational Resources Information Center

    Petersson, Gunnar; Nystrom, Maria

    2011-01-01

    The question of competence in providing music therapy has rarely been the focus of interest in empirical research, as most music therapy research aims at measuring outcomes. Therefore, the aim of this study is to analyse and describe musicians' learning processes when they study music therapy as a caring intervention. An initial presumption is…

  11. A Combined Motivation and Parent-Child Interaction Therapy Package Reduces Child Welfare Recidivism in a Randomized Dismantling Field Trial

    ERIC Educational Resources Information Center

    Chaffin, Mark; Funderburk, Beverly; Bard, David; Valle, Linda Anne; Gurwitch, Robin

    2011-01-01

    Objective: A package of parent-child interaction therapy (PCIT) combined with a self-motivational (SM) orientation previously was found in a laboratory trial to reduce child abuse recidivism compared with services as usual (SAU). Objectives of the present study were to test effectiveness in a field agency rather than in a laboratory setting and to…

  12. A Monte Carlo model for out-of-field dose calculation from high-energy photon therapy.

    PubMed

    Kry, Stephen F; Titt, Uwe; Followill, David; Pönisch, Falk; Vassiliev, Oleg N; White, R Allen; Stovall, Marilyn; Salehpour, Mohammad

    2007-09-01

    As cancer therapy becomes more efficacious and patients survive longer, the potential for late effects increases, including effects induced by radiation dose delivered away from the treatment site. This out-of-field radiation is of particular concern with high-energy radiotherapy, as neutrons are produced in the accelerator head. We recently developed an accurate Monte Carlo model of a Varian 2100 accelerator using MCNPX for calculating the dose away from the treatment field resulting from low-energy therapy. In this study, we expanded and validated our Monte Carlo model for high-energy (18 MV) photon therapy, including both photons and neutrons. Simulated out-of-field photon doses were compared with measurements made with thermoluminescent dosimeters in an acrylic phantom up to 55 cm from the central axis. Simulated neutron fluences and energy spectra were compared with measurements using moderated gold foil activation in moderators and data from the literature. The average local difference between the calculated and measured photon dose was 17%, including doses as low as 0.01% of the central axis dose. The out-of-field photon dose varied substantially with field size and distance from the edge of the field but varied little with depth in the phantom, except at depths shallower than 3 cm, where the dose sharply increased. On average, the difference between the simulated and measured neutron fluences was 19% and good agreement was observed with the neutron spectra. The neutron dose equivalent varied little with field size or distance from the central axis but decreased with depth in the phantom. Neutrons were the dominant component of the out-of-field dose equivalent for shallow depths and large distances from the edge of the treatment field. This Monte Carlo model is useful to both physicists and clinicians when evaluating out-of-field doses and associated potential risks.

  13. Pulsed light imaging for wide-field dosimetry of photodynamic therapy in the skin

    NASA Astrophysics Data System (ADS)

    Davis, Scott C.; Sexton, Kristian; Chapman, Michael Shane; Maytin, Edward; Hasan, Tayyaba; Pogue, Brian W.

    2014-03-01

    Photodynamic therapy using aminoluvelinic acid (ALA) is an FDA-approved treatment for actinic keratoses, pre-cancerous skin lesions which pose a significant risk for immunocompromised individuals, such as organ transplant recipients. While PDT is generally effective, response rates vary, largely due to variations in the accumulation of the photosensitizer protoporphyrin IX (PpIX) after ALA application. The ability to quantify PpIX production before treatment could facilitate the use of additional interventions to improve outcomes. While many groups have demonstrated the ability to image PpIX in the clinic, these systems generally require darkening the room lights during imaging, which is unpopular with clinicians. We have developed a novel wide-field imaging system based on pulsed excitation and gated acquisition to image photosensitizer activity in the skin. The tissue is illuminated using four pulsed LED's to excite PpIX, and the remitted light acquired with a synchronized ICCD. This approach facilitates real-time background subtraction of ambient light, precluding the need to darken the exam room. Delivering light in short bursts also allows the use of elevated excitation intensity while remaining under the maximum permissible exposure limits, making the modality more sensitive to photosensitizer fluorescence than standard approaches. Images of tissue phantoms indicate system sensitivity down to 250nM PpIX and images of animals demonstrate detection of PpIX fluorescence in vivo under normal room light conditions.

  14. Treatment of PTSD in Rwandan child genocide survivors using thought field therapy.

    PubMed

    Sakai, Caroline E; Connolly, Suzanne M; Oas, Paul

    2010-01-01

    Thought Field Therapy (TFT), which utilizes the self-tapping of specific acupuncture points while recalling a traumatic event or cue, was applied with 50 orphaned adolescents who had been suffering with symptoms of PTSD since the Rwandan genocide 12 years earlier. Following a single TFT session, scores on a PTSD checklist completed by caretakers and on a self-rated PTSD checklist had significantly decreased (p < .0001 on both measures). The number of participants exceeding the PTSD cutoffs decreased from 100% to 6% on the caregiver ratings and from 72% to 18% on the self-ratings. The findings were corroborated by informal interviews with the adolescents and the caregivers, which indicated dramatic reductions of PTSD symptoms such as flashbacks, nightmares, bedwetting, depression, isolation, difficulty concentrating, jumpiness, and aggression. Following the study, the use of TFT on a self-applied and peer-utilized basis became part of the culture at the orphanage, and on one-year follow-up the initial improvements had been maintained as shown on both checklists.

  15. Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits.

    PubMed

    Trivillin, Verónica A; Abramson, David B; Bumaguin, Gaston E; Bruno, Leandro J; Garabalino, Marcela A; Monti Hughes, Andrea; Heber, Elisa M; Feldman, Sara; Schwint, Amanda E

    2014-11-01

    Boron neutron capture synovectomy (BNCS) is explored for the treatment of rheumatoid arthritis (RA). The aim of the present study was to perform boron biodistribution studies in a model of antigen-induced arthritis (AIA) in female New Zealand rabbits, with the boron carriers boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) to assess the potential feasibility of BNCS for RA. Rabbits in chronic phase of AIA were used for biodistribution studies employing the following protocols: intra-articular (ia) (a) BPA-f 0.14 M (0.7 mg (10)B), (b) GB-10 (5 mg (10)B), (c) GB-10 (50 mg (10)B) and intravenous (iv), (d) BPA-f 0.14 M (15.5 mg (10)B/kg), (e) GB-10 (50 mg (10)B/kg), and (f) BPA-f (15.5 mg (10)B/kg) + GB-10 (50 mg (10)B/kg). At different post-administration times (13-85 min for ia and 3 h for iv), samples of blood, pathological synovium (target tissue), cartilage, tendon, muscle, and skin were taken for boron measurement by inductively coupled plasma mass spectrometry. The intra-articular administration protocols at <40 min post-administration both for BPA-f and GB-10, and intravenous administration protocols for GB-10 and [GB-10 + BPA-f] exhibited therapeutically useful boron concentrations (>20 ppm) in the pathological synovium. Dosimetric estimations suggest that BNCS would be able to achieve a therapeutically useful dose in pathological synovium without exceeding the radiotolerance of normal tissues in the treatment volume, employing boron carriers approved for use in humans. Radiobiological in vivo studies will be necessary to determine the actual therapeutic efficacy of BNCS to treat RA in an experimental model.

  16. Sequentially Programmed Magnetic Field Therapy in the Management of Recurrent Anaplastic Astrocytoma: A Case Report and Literature Review

    PubMed Central

    Vasishta, V.G.

    2010-01-01

    Background Anaplastic astrocytomas are progressive brain tumors with a tendency to infiltrate the surrounding tissue. Recurrence is very common, with recurrent tumors being extremely refractory to existing therapies. Case Presentation: A 33-year-old woman presented with a history of an unprovoked fall, followed by seizures. An MRI scan revealed a mass in the fronto-temporo-parietal region of the brain, suggesting a primary tumor. She underwent craniotomy and surgical debulking of the tumor. The histology of the tumor tissue revealed an anaplastic astrocytoma. Follow-up MRI scans indicated the presence of a residual, rapidly progressing tumor. A 6-week course of fractionated radiation and concurrent chemotherapy with Temodar® (temozolomide capsules) did not stop tumor progression. Intervention: Due to the failure of conventional therapies in preventing rapid disease progression, the patient volunteered to undergo a 28-day course of Sequentially Programmed Magnetic Field (SPMF) therapy. Results Immediate post-therapy MRI scan showed a cessation of tumor growth, and follow-up imaging at 6, 12, 24 and 36 months revealed a gradual but steady decrease in the size of the tumor. The patient reported an alleviation of clinical symptoms and a subjective improvement in the quality of life at 6, 12, 24 and 36 months following SPMF therapy. Conclusion The remarkable improvement of this patient suggests that SPMF therapy may be a valuable option for anaplastic astrocytoma, especially in recurrent and rapidly progressing tumors. PMID:20740195

  17. A comprehensive spectrometry study of a stray neutron radiation field in scanning proton therapy

    NASA Astrophysics Data System (ADS)

    Mares, Vladimir; Romero-Expósito, Maite; Farah, Jad; Trinkl, Sebastian; Domingo, Carles; Dommert, Martin; Stolarczyk, Liliana; Van Ryckeghem, Laurent; Wielunski, Marek; Olko, Pawel; Harrison, Roger M.

    2016-06-01

    The purpose of this study is to characterize the stray neutron radiation field in scanning proton therapy considering a pediatric anthropomorphic phantom and a clinically-relevant beam condition. Using two extended-range Bonner sphere spectrometry systems (ERBSS), Working Group 9 of the European Radiation Dosimetry Group measured neutron spectra at ten different positions around a pediatric anthropomorphic phantom irradiated for a brain tumor with a scanning proton beam. This study compares the different systems and unfolding codes as well as neutron spectra measured in similar conditions around a water tank phantom. The ten spectra measured with two ERBSS systems show a generally similar thermal component regardless of the position around the phantom while high energy neutrons (above 20 MeV) were only registered at positions near the beam axis (at 0°, 329° and 355°). Neutron spectra, fluence and ambient dose equivalent, H *(10), values of both systems were in good agreement (<15%) while the unfolding code proved to have a limited effect. The highest H *(10) value of 2.7 μSv Gy-1 was measured at 329° to the beam axis and 1.63 m from the isocenter where high-energy neutrons (E  ⩾  20 MeV) contribute with about 53%. The neutron mapping within the gantry room showed that H *(10) values significantly decreased with distance and angular position with respect to the beam axis dropping to 0.52 μSv Gy-1 at 90° and 3.35 m. Spectra at angles of 45° and 135° with respect to the beam axis measured here with an anthropomorphic phantom showed a similar peak structure at the thermal, fast and high energy range as in the previous water-tank experiments. Meanwhile, at 90°, small differences at the high-energy range were observed. Using ERBSS systems, neutron spectra mapping was performed to characterize the exposure of scanning proton therapy patients. The ten measured spectra provide precise information about the exposure of healthy organs to thermal

  18. Modern Radiation Therapy for Hodgkin Lymphoma: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group (ILROG)

    SciTech Connect

    Specht, Lena; Yahalom, Joachim; Illidge, Tim; Berthelsen, Anne Kiil; Constine, Louis S.; Eich, Hans Theodor; Girinsky, Theodore; Hoppe, Richard T.; Mauch, Peter; Mikhaeel, N. George; Ng, Andrea

    2014-07-15

    Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solely on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the

  19. Analysis of 18F-fluorodeoxy-glucose PET imaging data captured before and after Pc 4-mediated photodynamic therapy of U87 tumors in the athymic nude rat

    NASA Astrophysics Data System (ADS)

    Cross, Nathan; Varghai, Davood; Spring-Robinson, Chandra; Sharma, Rahul; Muzic, Raymond F., Jr.; Oleinick, Nancy L.; Dean, D.

    2007-02-01

    Introduction: Several workers have proposed the use of PET (Positron Emission Tomography) imaging for the outcome assessment of photodynamic therapy (PDT), especially for deep-seated tumors. We report on our study of 18Ffluorodeoxy- glucose (18F-FDG) PET imaging following brain tumor Pc4-PDT. Our working hypothesis was that the tumor's metabolic activity would decline dramatically following Pc 4-PDT owing to tumor necrosis. Methods: Seven days after intraparenchymal implantation of U87 cells, the brains of 12 athymic nude rats were imaged by micro-CT and/or micro-MR. These animals were also 18F-FDG micro-PET (μPET) scanned before and after Pc 4-PDT. 18F-FDG was used to trace metabolic activity that was monitored via μPET. Occurrence of PDT was confirmed on histology. The analysis of 18F-FDG dose and animal weight normalized μPET activity was studied over the 90 minute µPET scan. Results: Currently, μPET data have been studied for: (1) three of the animals that did not indicate tumor necrosis on histology and were assigned to a "Non-PDT" group, and (2) six animals that exhibited tumor necrosis on histology and were assigned to a "PDT" group. The μPET-detected 18F-FDG uptake activity in the tumor region before and after photoirradiation increased in the Non-PDT group an average of 2.28 times, and in the PDT group it increased an average of 1.15 times. Discussion: We are investigating the cause of the increase in 18F-FDG μPET activity that we observed in the PDT group. The methodology used in this study should be useful in determining whether this or other PET, SPECT, or MR functional imaging protocols will detect both the specificity and sensitivity of brain tumor necrosis following Pc 4-PDT.

  20. Long-term infusions of p-boronophenylalanine for boron neutron capture therapy: evaluation using rat brain tumor and spinal cord models.

    PubMed

    Morris, G M; Micca, P L; Nawrocky, M M; Weissfloch, L E; Coderre, J A

    2002-12-01

    Rat 9L gliosarcoma cells infiltrating the normal brain have been shown previously to accumulate only approximately 30% as much boron as the intact tumor after administration of the boronated amino acid p-boronophenylalanine (BPA). Long-term i.v. infusions of BPA were shown previously to increase the boron content of these infiltrating tumor cells significantly. Experiments to determine whether this improved BPA distribution into infiltrating tumor cells after a long-term i.v. infusion improves tumor control after BNCT in this brain tumor model and whether it has any deleterious effects in the response of the rat spinal cord to BNCT are the subjects of the present report. BPA was administered in a fructose solution at a dose of 650 mg BPA/kg by single i.p. injection or by i.v. infusion for 2 h or 6 h, at 330 mg BPA/kg h(-1). At 1 h after the end of either the 2-h or the 6-h infusion, the CNS:blood (10)B partition ratio was 0.9:1. At 3 h after the single i.p. injection, the ratio was 0.6:1. After spinal cord irradiations, the ED(50) for myeloparesis was 14.7 +/- 0.4 Gy after i.p. administration of BPA and 12.9 +/- 0.3 Gy in rats irradiated after a 6-h i.v. infusion of BPA; these values were significantly different (P < 0.001). After irradiation with 100 kVp X rays, the ED(50) was 18.6 +/- 0.1 Gy. The boron compound biological effectiveness (CBE) factors calculated for the boron neutron capture dose component were 1.2 +/- 0.1 for the i.p. BPA administration protocol and 1.5 +/- 0.1 after irradiation using the 6-h i.v. BPA infusion protocol (P < 0.05). In the rat 9L gliosarcoma brain tumor model, the blood boron concentrations at 1 h after the end of the 2-h infusion (330 mg BPA/kg h(-1); n = 15) or after the 6-h infusion (190 mg BPA/kg h(-1); n = 13) were 18.9 +/- 2.2 microg 10B/g and 20.7 +/- 1.8 microg 10B/g, respectively. The irradiation times were adjusted individually, based on the preirradiation blood sample, to deliver a predicted 50% tumor control dose of 8

  1. SU-E-T-296: Single Field Per Day Vs. Multiple Fields Per Day and the Impact On BED in Proton Therapy Treatment

    SciTech Connect

    Grantham, K; Wooten, H; Zhao, T; Klein, E

    2014-06-01

    Purpose: A common practice, in proton therapy, is to deliver a rotating subset of fields from the treatment plan for the daily fractions. This study compares the impact this practice has on the biological effective dose (BED) versus delivering all planned fields daily. Methods: For two scenarios (a phantom with a geometry approximating the anatomy of a prostate treatment with opposing lateral beams, and a clinical 3-field brain treatment), treatment plans were produced in Eclipse (Varian) to simulate delivery of one, two, and three fields per fraction. The RT-Dose file, structure set, and α/β ratios were processed using in-house MATLAB code to return a new RT-Dose file containing the BED (including a proton RBE of 1.1) which was imported back into Eclipse for analysis. Results: For targets and regions of field overlap in the treatment plan, BED is not affected by delivery regimen. In the phantom, BED in the femoral heads showed increased by 20% when a single field was used rather than two fields. In the brain treatment, the minimum BED to the left optic nerve and the pituitary gland increased by 13% and 10% respectively, for a one-field regime compared to three-fields per fraction. Comparing the two-field and threefield regimes, the optic nerve BED was not significantly affected and the minimum pituitary BED was 4% higher for two fields per day. Conclusion: Hypo-fractionation effects, in regions of non-overlap of fields, significantly increase the BED to the involved tissues by as much as 20%. Care should be taken to avoid inadvertently sacrificing plan effectiveness in the interest of reduced treatment time.

  2. Sound Field Amplification: Effects on Managerial Time in Small Group Speech Therapy

    ERIC Educational Resources Information Center

    Meeks, Jeffrey Craig

    2011-01-01

    This study addresses the use of speech amplification devices in speech therapy sessions. The major factor addressed is the impact that speech amplification has upon the managerial time of speech-language pathologists who provide therapy in small group sessions. This study measured the change in the amount of time speech-language pathologists spent…

  3. Estimation of capture zones and drawdown at the Northwest and West Well Fields, Miami-Dade County, Florida, using an unconstrained Monte Carlo analysis: recent (2004) and proposed conditions

    USGS Publications Warehouse

    Brakefield, Linzy K.; Hughes, Joseph D.; Langevin, Christian D.; Chartier, Kevin

    2013-01-01

    Travel-time capture zones and drawdown for two production well fields, used for drinking-water supply in Miami-Dade County, southeastern Florida, were delineated by the U.S Geological Survey using an unconstrained Monte Carlo analysis. The well fields, designed to supply a combined total of approximately 250 million gallons of water per day, pump from the highly transmissive Biscayne aquifer in the urban corridor between the Everglades and Biscayne Bay. A transient groundwater flow model was developed and calibrated to field data to ensure an acceptable match between simulated and observed values for aquifer heads and net exchange of water between the aquifer and canals. Steady-state conditions were imposed on the transient model and a post-processing backward particle-tracking approach was implemented. Multiple stochastic realizations of horizontal hydraulic conductivity, conductance of canals, and effective porosity were simulated for steady-state conditions representative of dry, average and wet hydrologic conditions to calculate travel-time capture zones of potential source areas of the well fields. Quarry lakes, formed as a product of rock-mining activities, whose effects have previously not been considered in estimation of capture zones, were represented using high hydraulic-conductivity, high-porosity cells, with the bulk hydraulic conductivity of each cell calculated based on estimates of aquifer hydraulic conductivity, lake depths and aquifer thicknesses. A post-processing adjustment, based on calculated residence times using lake outflows and known lake volumes, was utilized to adjust particle endpoints to account for an estimate of residence-time-based mixing of lakes. Drawdown contours of 0.1 and 0.25 foot were delineated for the dry, average, and wet hydrologic conditions as well. In addition, 95-percent confidence intervals (CIs) were calculated for the capture zones and drawdown contours to delineate a zone of uncertainty about the median estimates

  4. Triple Therapy of HER2(+) Cancer Using Radiolabeled Multifunctional Iron Oxide Nanoparticles and Alternating Magnetic Field.

    PubMed

    Zolata, Hamidreza; Afarideh, Hossein; Davani, Fereydoun Abbasi

    2016-11-01

    By using radio-labeled multifunctional superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF), we carried out targeted hyperthermia, drug delivery, radio-immunotherapy (RIT), and controlled chemotherapy of cancer tumors. We synthesized and characterized Indium-111-labeled, Trastuzumab and Doxorubicin (DOX)-conjugated APTES-PEG-coated SPIONs in our previous work. Then, we evaluated their capability in SPECT/MRI (single photon emission computed tomography/magnetic resonance imaging) dual modal molecular imaging, targeting, and controlled release. In this research, AMF was introduced to evaluate therapeutic effects of magnetic hyperthermia on radionuclide-chemo therapy of HER2(+) cells and tumor (HER2(+))-bearing mice. In vitro and in vivo experiments using synthesized complex were repeated under an AMF (f: 100 KHz, H: 280 Gs). Instead of an intra-tumor injection in most hyperthermia experiments, SPIONs were injected to the tail vein, based on our delivery strategies. For magnetic delivery, we held a permanent Nd-B-Fe magnet near the tumor region. The results showed that simultaneous magnetic hyperthermia enhanced SKBR3 cancer cells, killing by 24%, 28%, 33%, and 80% at 48 hours post-treatment for treated cells with (1) bare SPIONs; (2) antibody-conjugated, DOX-free, surface-modified SPIONs; (3) (111)In-labeled, antibody-conjugated surface-modified SPIONs; and (4) (111)In-labeled, antibody- and DOX-conjugated surface-modified SPIONs, respectively. Moreover, tumor volume inhibitory rate was 85% after a 28 day period of treatment. By using this method, multimodal imaging-guided, targeted hyperthermia, RIT, and controlled chemotherapy could be achievable in the near future.

  5. Enhancing Foster Parent Training with Parent-Child Interaction Therapy: Evidence from a Randomized Field Experiment

    PubMed Central

    Mersky, Joshua P.; Topitzes, James; Janczewski, Colleen E.; McNeil, Cheryl B.

    2015-01-01

    Objective Research indicates that foster parents often do not receive sufficient training and support to help them meet the demands of caring for foster children with emotional and behavioral disturbances. Parent-Child Interaction Therapy (PCIT) is a clinically efficacious intervention for child externalizing problems, and it also has been shown to mitigate parenting stress and enhance parenting attitudes and behaviors. However, PCIT is seldom available to foster families, and it rarely has been tested under intervention conditions that are generalizable to community-based child welfare service contexts. To address this gap, PCIT was adapted and implemented in a field experiment using 2 novel approaches—group-based training and telephone consultation—both of which have the potential to be integrated into usual care. Method This study analyzes 129 foster-parent-child dyads who were randomly assigned to 1 of 3 conditions: (a) waitlist control, (b) brief PCIT, and (c) extended PCIT. Self-report and observational data were gathered at multiple time points up to 14 weeks post baseline. Results Findings from mixed-model, repeated measures analyses indicated that the brief and extended PCIT interventions were associated with a significant decrease in self-reported parenting stress. Results from mixed-effects generalized linear models showed that the interventions also led to significant improvements in observed indicators of positive and negative parenting. The brief course of PCIT was as efficacious as the extended PCIT intervention. Conclusions The findings suggest that usual training and support services can be improved upon by introducing foster parents to experiential, interactive PCIT training. PMID:26977251

  6. Designing and Dosimetry of a Shield for Photon Fields of Radiation Therapy in Oral Cavity Cancer.

    PubMed

    Jabbari, Keyvan; Senobari, Somayeh; Roayaei, Mahnaz; Rostampour, Masoumeh

    2015-01-01

    The cancer of oral cavity is related to lesions of mucous membrane of tongue and gum that can be treated with radiation therapy. A lateral photon field can be used to treat this kind of tumor, which has a side-effect on normal tissue in the opposite side of the oral cavity. In this study the dosimetric effect of the various shields in oral cavity is evaluated. In this study, a special phantom similar to the structure of oral cavity with capability of film dosimetry was designed and constructed. The various shield slabs were made of five materials: Lead, Plexiglas, Acrylic resin, Silicon and Plaster. For irradiation, Cobalt 60 (60Co) and 6 MV photon beams were used. The film dosimetry before and after the shield was performed using GAFCHROMIC EBT2 films. The film before the shield measures the magnitude of backscattering radiation from the shield. The prescribed dose was 150 cGy. Results showed that 3 cm of the lead in both energies had the maximum absorption of radiation. The absorbed dose to opposite side of shield for 6 MV photon beams and 60Co were 21 and 32 cGy, respectively. The minimum attenuation on radiation was observed in silicon shield for which the dose of opposite side were 116 and 147 cGy for 6 MV and 60Co respectively. The maximum backscattered dose was measured 177 cGy and 219 cGy using 3 cm thickness of lead, which was quite considerable. The minimum backscattering where for acrylic resin 101 and 118 cGy for 6 MV and cobalt. In this study, it was concluded that the amount of backscattering for 3 cm Lead shield is quite considerable and increases the dose significantly. A composite layer of shield with 1-2 cm lead and 1 cm acrylic resin can have the protective effect and low backscattering radiation at the same time.

  7. Designing and Dosimetry of a Shield for Photon Fields of Radiation Therapy in Oral Cavity Cancer

    PubMed Central

    Jabbari, Keyvan; Senobari, Somayeh; Roayaei, Mahnaz; Rostampour, Masoumeh

    2015-01-01

    The cancer of oral cavity is related to lesions of mucous membrane of tongue and gum that can be treated with radiation therapy. A lateral photon field can be used to treat this kind of tumor, which has a side-effect on normal tissue in the opposite side of the oral cavity. In this study the dosimetric effect of the various shields in oral cavity is evaluated. In this study, a special phantom similar to the structure of oral cavity with capability of film dosimetry was designed and constructed. The various shield slabs were made of five materials: Lead, Plexiglas, Acrylic resin, Silicon and Plaster. For irradiation, Cobalt 60 (60Co) and 6 MV photon beams were used. The film dosimetry before and after the shield was performed using GAFCHROMIC EBT2 films. The film before the shield measures the magnitude of backscattering radiation from the shield. The prescribed dose was 150 cGy. Results showed that 3 cm of the lead in both energies had the maximum absorption of radiation. The absorbed dose to opposite side of shield for 6 MV photon beams and 60Co were 21 and 32 cGy, respectively. The minimum attenuation on radiation was observed in silicon shield for which the dose of opposite side were 116 and 147 cGy for 6 MV and 60Co respectively. The maximum backscattered dose was measured 177 cGy and 219 cGy using 3 cm thickness of lead, which was quite considerable. The minimum backscattering where for acrylic resin 101 and 118 cGy for 6 MV and cobalt. In this study, it was concluded that the amount of backscattering for 3 cm Lead shield is quite considerable and increases the dose significantly. A composite layer of shield with 1–2 cm lead and 1 cm acrylic resin can have the protective effect and low backscattering radiation at the same time. PMID:26120570

  8. Enhancing Predicted Efficacy of Tumor Treating Fields Therapy of Glioblastoma Using Targeted Surgical Craniectomy: A Computer Modeling Study

    PubMed Central

    Korshoej, Anders Rosendal; Saturnino, Guilherme Bicalho; Rasmussen, Line Kirkegaard; von Oettingen, Gorm; Sørensen, Jens Christian Hedemann; Thielscher, Axel

    2016-01-01

    Objective The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. Methods We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic clinical scenarios. Results For the superficial tumor, removal of a standard craniotomy bone flap increased the electrical field strength by 60–70% in the tumor. The percentage of tissue in expected growth arrest or regression was increased from negligible values to 30–50%. The observed effects were highly focal and targeted at the regions of pathology underlying the craniectomy. No significant changes were observed in surrounding healthy tissues. Median field strengths in tumor tissue increased with increasing craniectomy diameter up to 50–70 mm. Multiple smaller burr holes were more efficient than single craniectomies of equivalent area. Craniectomy caused no significant field enhancement in the deeply seated tumor, but rather a focal enhancement in the brain tissue underlying the skull defect. Conclusions Our results provide theoretical evidence that small and clinically feasible craniectomies may provide significant enhancement of TTFields intensity in cerebral hemispheric tumors without severely compromising brain protection or causing unacceptable heating in

  9. Towards the optimisation of acoustic fields for ablative therapies of tumours in the upper abdomen

    NASA Astrophysics Data System (ADS)

    Gélat, P.; ter Haar, G.; Saffari, N.

    2013-08-01

    The efficacy of high intensity focused ultrasound (HIFU) for the non-invasive treatment of cancer has been demonstrated for a range of different cancers including those of the liver, kidney, prostate and breast. As a non-invasive focused therapy, HIFU offers considerable advantages over other techniques such as chemotherapy and surgical resection, in terms of its non-invasiveness and low risk of harmful side effects. There is, however, a number of significant challenges which currently hinder its widespread clinical application. One of these challenges is the need to transmit sufficient energy through the ribcage to induce tissue necrosis at the required foci whilst minimising the formation of side lobes and sparing healthy tissue. Ribs both absorb and reflect ultrasound strongly. As such, a common side effect of focusing ultrasound in regions located behind the rib cage is the overheating of bone and surrounding tissue, which can lead to skin burns. Successful treatment of a patient with tumours in the upper abdomen therefore requires a thorough understanding of the way acoustic and thermal energy are deposited. This is likely to rely on a treatment planning procedure in which optimal source velocity distributions are obtained so as to maximise a dose quantity at the treatment sites, whilst ensuring that this quantity does not exceed a specified threshold at other field locations, particularly on the surface of the ribs. Previously, a boundary element approach based on a Generalised Minimal Residual (GMRES) implementation of the Burton-Miller formulation was developed to predict the field of a multi-element HIFU array scattered by human ribs, the topology of which was obtained from CT scan data [1]. This work describes the reformulation of the boundary element equations as a least-squares minimisation problem with non-linear constraints. The methodology was subsequently tested at an excitation frequency of 100 kHz on a spherical multi-element array in the presence

  10. Split-field vs extended-field intensity-modulated radiation therapy plans for oropharyngeal cancer: Which spares the larynx? Which spares the thyroid?

    SciTech Connect

    Yu, Yao; Chen, Josephine; Leary, Celeste I.; Shugard, Erin; Yom, Sue S.

    2016-07-01

    Radiation of the low neck can be accomplished using split-field intensity-modulated radiation therapy (sf-IMRT) or extended-field intensity-modulated radiation therapy (ef-IMRT). We evaluated the effect of these treatment choices on target coverage and thyroid and larynx doses. Using data from 14 patients with cancers of the oropharynx, we compared the following 3 strategies for radiating the low neck: (1) extended-field IMRT, (2) traditional split-field IMRT with an initial cord-junction block to 40 Gy, followed by a full-cord block to 50 Gy, and (3) split-field IMRT with a full-cord block to 50 Gy. Patients were planned using each of these 3 techniques. To facilitate comparison, extended-field plans were normalized to deliver 50 Gy to 95% of the neck volume. Target coverage was assessed using the dose to 95% of the neck volume (D{sub 95}). Mean thyroid and larynx doses were computed. Extended-field IMRT was used as the reference arm; the mean larynx dose was 25.7 ± 7.4 Gy, and the mean thyroid dose was 28.6 ± 2.4 Gy. Split-field IMRT with 2-step blocking reduced laryngeal dose (mean larynx dose 15.2 ± 5.1 Gy) at the cost of a moderate reduction in target coverage (D{sub 95} 41.4 ± 14 Gy) and much higher thyroid dose (mean thyroid dose 44.7 ± 3.7 Gy). Split-field IMRT with initial full-cord block resulted in greater laryngeal sparing (mean larynx dose 14.2 ± 5.1 Gy) and only a moderately higher thyroid dose (mean thyroid dose 31 ± 8 Gy) but resulted in a significant reduction in target coverage (D{sub 95} 34.4 ± 15 Gy). Extended-field IMRT comprehensively covers the low neck and achieves acceptable thyroid and laryngeal sparing. Split-field IMRT with a full-cord block reduces laryngeal doses to less than 20 Gy and spares the thyroid, at the cost of substantially reduced coverage of the low neck. Traditional 2-step split-field IMRT similarly reduces the laryngeal dose but also reduces low-neck coverage and delivers very high doses to the thyroid.

  11. Split-field vs extended-field intensity-modulated radiation therapy plans for oropharyngeal cancer: Which spares the larynx? Which spares the thyroid?

    PubMed

    Yu, Yao; Chen, Josephine; Leary, Celeste I; Shugard, Erin; Yom, Sue S

    2016-01-01

    Radiation of the low neck can be accomplished using split-field intensity-modulated radiation therapy (sf-IMRT) or extended-field intensity-modulated radiation therapy (ef-IMRT). We evaluated the effect of these treatment choices on target coverage and thyroid and larynx doses. Using data from 14 patients with cancers of the oropharynx, we compared the following 3 strategies for radiating the low neck: (1) extended-field IMRT, (2) traditional split-field IMRT with an initial cord-junction block to 40Gy, followed by a full-cord block to 50Gy, and (3) split-field IMRT with a full-cord block to 50Gy. Patients were planned using each of these 3 techniques. To facilitate comparison, extended-field plans were normalized to deliver 50Gy to 95% of the neck volume. Target coverage was assessed using the dose to 95% of the neck volume (D95). Mean thyroid and larynx doses were computed. Extended-field IMRT was used as the reference arm; the mean larynx dose was 25.7 ± 7.4Gy, and the mean thyroid dose was 28.6 ± 2.4Gy. Split-field IMRT with 2-step blocking reduced laryngeal dose (mean larynx dose 15.2 ± 5.1Gy) at the cost of a moderate reduction in target coverage (D95 41.4 ± 14Gy) and much higher thyroid dose (mean thyroid dose 44.7 ± 3.7Gy). Split-field IMRT with initial full-cord block resulted in greater laryngeal sparing (mean larynx dose 14.2 ± 5.1Gy) and only a moderately higher thyroid dose (mean thyroid dose 31 ± 8Gy) but resulted in a significant reduction in target coverage (D95 34.4 ± 15Gy). Extended-field IMRT comprehensively covers the low neck and achieves acceptable thyroid and laryngeal sparing. Split-field IMRT with a full-cord block reduces laryngeal doses to less than 20Gy and spares the thyroid, at the cost of substantially reduced coverage of the low neck. Traditional 2-step split-field IMRT similarly reduces the laryngeal dose but also reduces low-neck coverage and delivers very high doses to the thyroid.

  12. Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies

    SciTech Connect

    Salama, Joseph K. . E-mail: jsalama@radonc.uchicago.edu; Mundt, Arno J.; Roeske, John; Mehta, Neil

    2006-07-15

    Purpose: The aim of this article is to report a preliminary analysis of our initial clinical experience with extended-field intensity-modulated radiotherapy for gynecologic malignancies. Methods and Materials: Between November 2002 and May 2005, 13 women with gynecologic malignancies were treated with extended-field radiation therapy. Of the women, 7 had endometrial cancer, 4 cervical cancer, 1 recurrent endometrial cancer, and 1 suspected cervical cancer. All women underwent computed tomography planning, with the upper vagina, parametria, and uterus (if present) contoured within the CTV. In addition, the clinical target volume contained the pelvic and presacral lymph nodes as well as the para-aortic lymph nodes. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE v 3.0). All late toxicity was scored using the Radiation Therapy Oncology Group late toxicity score. Results: The median follow-up was 11 months. Extended-field intensity-modulated radiation therapy (IMRT) for gynecologic malignancies was well tolerated. Two patients experienced Grade 3 or higher toxicity. Both patients were treated with concurrent cisplatin based chemotherapy. Neither patient was planned with bone marrow sparing. Eleven patients had no evidence of late toxicity. One patient with multiple previous surgeries experienced a bowel obstruction. One patient with bilateral grossly involved and unresectable common iliac nodes experienced bilateral lymphedema. Extended-field-IMRT achieved good local control with only 1 patient, who was metastatic at presentation, and 1 patient not able to complete treatment, experiencing in-field failure. Conclusions: Extended-field IMRT is safe and effective with a low incidence of acute toxicity. Longer follow-up is needed to assess chronic toxicity, although early results are promising.

  13. Video Screen Capture Basics

    ERIC Educational Resources Information Center

    Dunbar, Laura

    2014-01-01

    This article is an introduction to video screen capture. Basic information of two software programs, QuickTime for Mac and BlueBerry Flashback Express for PC, are also discussed. Practical applications for video screen capture are given.

  14. Exploring the influence of gestalt therapy training on psychiatric nursing practice: stories from the field.

    PubMed

    Kelly, Teresa; Howie, Linsey

    2011-08-01

    Psychiatric nurses interested in extending their interpersonal and psychotherapeutic skills sometimes undertake postgraduate training in gestalt therapy. Little is known about how this new knowledge and psychotherapeutic skill base informs their practice. This paper presents the findings of a qualitative study that aimed to explore the influence of gestalt therapy training on psychiatric nursing practice. Within a framework of narrative inquiry, four psychiatric nurses trained in gestalt therapy were invited to tell their stories of training in a gestalt approach to therapy, and recount their experiences of how it influenced their practice. In keeping with narrative analysis methods, the research findings were presented as a collection of four stories. Eight themes were derived from a thematic analysis conducted within and across the four stories. The discussion of the themes encapsulates the similarities and differences across the storied collection, providing a community and cultural context for understanding the individual stories.

  15. Assessment of radiation-induced second cancer risks in proton therapy and IMRT for organs inside the primary radiation field.

    PubMed

    Paganetti, Harald; Athar, Basit S; Moteabbed, Maryam; A Adams, Judith; Schneider, Uwe; Yock, Torunn I

    2012-10-07

    There is clinical evidence that second malignancies in radiation therapy occur mainly within the beam path, i.e. in the medium or high-dose region. The purpose of this study was to assess the risk for developing a radiation-induced tumor within the treated volume and to compare this risk for proton therapy and intensity-modulated photon therapy (IMRT). Instead of using data for specific patients we have created a representative scenario. Fully contoured age- and gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a treatment planning system and tumor volumes were contoured based on patients treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for IMRT and proton therapy treatments were generated. Lifetime attributable risks (LARs) for developing a second malignancy were calculated using a risk model considering cell kill, mutation, repopulation, as well as inhomogeneous organ doses. For standard fractionation schemes, the LAR for developing a second malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year old optic glioma patient treated with IMRT considering a soft-tissue carcinoma risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14 year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma cases the risks based on a sarcoma model were typically higher than the carcinoma risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from proton therapy turned out to be lower by at least a factor of 2 and up to a factor of 10. This is mainly due to lower total energy deposited in the patient when using proton beams. However, the comparison of a three-field and four-field proton plan also shows that the distribution of the dose, i.e. the particular treatment plan, plays a role. When using different fractionation schemes, the estimated risks roughly scale with the total dose difference in%. In conclusion, proton therapy can

  16. Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours.

    PubMed

    Sakurai, Yoshinori; Ono, Koji; Miyatake, Shin-Ichi; Maruhashi, Akira

    2006-03-07

    Boron neutron capture therapy (BNCT) without craniotomy for malignant brain tumours was started using an epi-thermal neutron beam at the Kyoto University Reactor in June 2002. We have tried some techniques to overcome the treatable-depth limit in BNCT. One of the effective techniques is void formation utilizing a tumour-removed cavity. The tumorous part is removed by craniotomy about 1 week before a BNCT treatment in our protocol. Just before the BNCT irradiation, the cerebro-spinal fluid (CSF) in the tumour-removed cavity is drained out, air is infused to the cavity and then the void is made. This void improves the neutron penetration, and the thermal neutron flux at depth increases. The phantom experiments and survey simulations modelling the CSF drainage and air infusion of the tumour-removed cavity were performed for the size and shape of the void. The advantage of the CSF drainage and air infusion is confirmed for the improvement in the depth-dose distribution. From the parametric surveys, it was confirmed that the cavity volume had good correlation with the improvement effect, and the larger effect was expected as the cavity volume was larger.

  17. Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours

    NASA Astrophysics Data System (ADS)

    Sakurai, Yoshinori; Ono, Koji; Miyatake, Shin-ichi; Maruhashi, Akira

    2006-03-01

    Boron neutron capture therapy (BNCT) without craniotomy for malignant brain tumours was started using an epi-thermal neutron beam at the Kyoto University Reactor in June 2002. We have tried some techniques to overcome the treatable-depth limit in BNCT. One of the effective techniques is void formation utilizing a tumour-removed cavity. The tumorous part is removed by craniotomy about 1 week before a BNCT treatment in our protocol. Just before the BNCT irradiation, the cerebro-spinal fluid (CSF) in the tumour-removed cavity is drained out, air is infused to the cavity and then the void is made. This void improves the neutron penetration, and the thermal neutron flux at depth increases. The phantom experiments and survey simulations modelling the CSF drainage and air infusion of the tumour-removed cavity were performed for the size and shape of the void. The advantage of the CSF drainage and air infusion is confirmed for the improvement in the depth-dose distribution. From the parametric surveys, it was confirmed that the cavity volume had good correlation with the improvement effect, and the larger effect was expected as the cavity volume was larger.

  18. Capture Their Attention: Capturing Lessons Using Screen Capture Software

    ERIC Educational Resources Information Center

    Drumheller, Kristina; Lawler, Gregg

    2011-01-01

    When students miss classes for university activities such as athletic and academic events, they inevitably miss important class material. Students can get notes from their peers or visit professors to find out what they missed, but when students miss new and challenging material these steps are sometimes not enough. Screen capture and recording…

  19. TU-CD-304-07: Intensity Modulated Electron Beam Therapy Employing Small Fields in Virtual Scanning Mode

    SciTech Connect

    Rodrigues, A; Yin, F; Wu, Q; Liang, B

    2015-06-15

    Purpose: Dynamic electron radiation therapies such as dynamic electron arc radiotherapy (DEAR) utilize small fields to provide target conformity and fluence modulation. The purpose of this study is to demonstrate the feasibility of virtual scanning mode using small fields. Methods: Monte Carlo simulations (EGSnrc/BEAMnrc/DOSXYZnrc) were performed using validated Varian TrueBeam phase space files for electron beam energies of 6, 9, 12, and 16 MeV and square/circular fields (1×1/1, 2×2/2, 3×3/3, 4×4/4, 5×5/5 cm{sup 2}/cm diameter). Resulting dose distributions (kernels) were used for subsequent calculations. The following analyses were performed: (1) Comparison of composite square fields and reference 10×10 cm{sup 2} dose distributions and (2) Scanning beam deliveries for square and circular fields realized as the convolution of kernels and scanning pattern. Preliminary beam weight and pattern optimization were also performed. Two linear scans of 10 cm with/without overlap were modeled. Comparison metrics included depth and orthogonal profiles at dmax. Results: (1) Composite fields regained reference depth dose profiles for most energies and fields within 5%. Smaller kernels and higher energies increased dose in the build-up and Bremsstrahlung region (30%, 16MeV and 1×1 cm{sup 2}), while reference dmax was maintained for all energies and composite fields. Smaller kernels (<2×2 cm{sup 2}) maintained penumbra and field size within 0.2 cm, and flatness within 2%. Deterioration of penumbra for larger kernels (5×5 cm{sup 2}) were observed. Balancing desirable dosimetry and efficiencies suggests that smaller kernels are used at edges and larger kernels in the center of the target. (2) Beam weight optimization improved cross-plane penumbra (0.2 cm) and increased the field size (0.4 cm) on average. In-plane penumbra and field size remained unchanged. Overlap depended on kernel size and optimal overlap resulted in flatness ±2%. Conclusion: Dynamic electron beam

  20. Comparison of out-of-field photon doses in 6 MV IMRT and neutron doses in proton therapy for adult and pediatric patients

    NASA Astrophysics Data System (ADS)

    Athar, Basit S.; Bednarz, Bryan; Seco, Joao; Hancox, Cindy; Paganetti, Harald

    2010-05-01

    The purpose of this study was to assess lateral out-of-field doses in 6 MV IMRT (intensity modulated radiation therapy) and compare them with secondary neutron equivalent dose contributions in proton therapy. We simulated out-of-field photon doses to various organs as a function of distance, patient's age, gender and treatment volumes based on 3, 6, 9 cm field diameters in the head and neck and spine region. The out-of-field photon doses to organs near the field edge were found to be in the range of 2, 5 and 10 mSv Gy-1 for 3 cm, 6 cm and 9 cm diameter IMRT fields, respectively, within 5 cm of the field edge. Statistical uncertainties calculated in organ doses vary from 0.2% to 40% depending on the organ location and the organ volume. Next, a comparison was made with previously calculated neutron equivalent doses from proton therapy using identical field arrangements. For example, out-of-field doses for IMRT to lung and uterus (organs close to the 3 cm diameter spinal field) were computed to be 0.63 and 0.62 mSv Gy-1, respectively. These numbers are found to be a factor of 2 smaller than the corresponding out-of-field doses for proton therapy, which were estimated to be 1.6 and 1.7 mSv Gy-1 (RBE), respectively. However, as the distance to the field edge increases beyond approximately 25 cm the neutron equivalent dose from proton therapy was found to be a factor of 2-3 smaller than the out-of-field photon dose from IMRT. We have also analyzed the neutron equivalent doses from an ideal scanned proton therapy (assuming not significant amount of absorbers in the treatment head). Out-of-field doses were found to be an order of magnitude smaller compared to out-of-field doses in IMRT or passive scattered proton therapy. In conclusion, there seem to be three geometrical areas when comparing the out-of-target dose from IMRT and (passive scattered) proton treatments. Close to the target (in-field, not analyzed here) protons offer a distinct advantage due to the lower

  1. Cryogenic Carbon Capture

    SciTech Connect

    2010-07-15

    IMPACCT Project: SES is developing a process to capture CO2 from the exhaust gas of coal-fired power plants by desublimation - the conversion of a gas to a solid. Capturing CO2 as a solid and delivering it as a liquid avoids the large energy cost of CO2 gas compression. SES’ capture technology facilitates the prudent use of available energy resources. Coal is our most abundant energy resource and is an excellent fuel for baseline power production. SES capture technology can capture 99% of the CO2 emissions in addition to a wide range of other pollutants more efficiently and at lower costs than existing capture technologies. SES’ capture technology can be readily added to our existing energy infrastructure.

  2. Modern radiation therapy for extranodal lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group.

    PubMed

    Yahalom, Joachim; Illidge, Tim; Specht, Lena; Hoppe, Richard T; Li, Ye-Xiong; Tsang, Richard; Wirth, Andrew

    2015-05-01

    Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL, involving any organ in the body and the spectrum of histological sub-types, poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU), as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype, anatomy, the treatment intent, and other treatment modalities that may be have been used before RT.

  3. Modern Radiation Therapy for Extranodal Lymphomas: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group

    SciTech Connect

    Yahalom, Joachim; Illidge, Tim; Specht, Lena; Hoppe, Richard T.; Li, Ye-Xiong; Tsang, Richard; Wirth, Andrew

    2015-05-01

    Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL, involving any organ in the body and the spectrum of histological sub-types, poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU), as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype, anatomy, the treatment intent, and other treatment modalities that may be have been used before RT.

  4. High-throughput phenotyping (HTP) identifies seedling root traits linked to variation in seed yield and nutrient capture in field-grown oilseed rape (Brassica napus L.)

    PubMed Central

    Thomas, C. L.; Graham, N. S.; Hayden, R.; Meacham, M. C.; Neugebauer, K.; Nightingale, M.; Dupuy, L. X.; Hammond, J. P.; White, P. J.; Broadley, M. R.

    2016-01-01

    Background and Aims Root traits can be selected for crop improvement. Techniques such as soil excavations can be used to screen root traits in the field, but are limited to genotypes that are well-adapted to field conditions. The aim of this study was to compare a low-cost, high-throughput root phenotyping (HTP) technique in a controlled environment with field performance, using oilseed rape (OSR; Brassica napus) varieties. Methods Primary root length (PRL), lateral root length and lateral root density (LRD) were measured on 14-d-old seedlings of elite OSR varieties (n = 32) using a ‘pouch and wick’ HTP system (∼40 replicates). Six field experiments were conducted using the same varieties at two UK sites each year for 3 years. Plants were excavated at the 6- to 8-leaf stage for general vigour assessments of roots and shoots in all six experiments, and final seed yield was determined. Leaves were sampled for mineral composition from one of the field experiments. Key Results Seedling PRL in the HTP system correlated with seed yield in four out of six (r = 0·50, 0·50, 0·33, 0·49; P < 0·05) and with emergence in three out of five (r = 0·59, 0·22, 0·49; P < 0·05) field experiments. Seedling LRD correlated positively with leaf concentrations of some minerals, e.g. calcium (r = 0·46; P < 0·01) and zinc (r = 0·58; P < 0·001), but did not correlate with emergence, general early vigour or yield in the field. Conclusions Associations between PRL and field performance are generally related to early vigour. These root traits might therefore be of limited additional selection value, given that vigour can be measured easily on shoots/canopies. In contrast, LRD cannot be assessed easily in the field and, if LRD can improve nutrient uptake, then it may be possible to use HTP systems to screen this trait in both elite and more genetically diverse, non-field-adapted OSR. PMID:27052342

  5. Comparison of second cancer risk due to out-of-field doses from 6-MV IMRT and proton therapy based on 6 pediatric patient treatment plans

    PubMed Central

    Athar, Basit S.; Paganetti, Harald

    2010-01-01

    Background and Purpose This study compared 6-MV IMRT and proton therapy in terms of organ specific second cancer lifetime attributable risks (LARs) caused by scattered and secondary out-of-field radiation. Material and Methods Based on simulated organ doses, excess relative and excess absolute risk models were applied to assess organ-specific LARs. Two treatment sites (cranium and central spine) were considered involving 6 treatment volumes and 6 patient ages (9-month, 4-year, 8-year, 11-year, 14-year, and adult). Results The LARs for thyroid cancer from a 6 cm diameter field treating a brain lesion in a 4-year old patient were estimated to be 1.1% and 0.3% in passive proton therapy and IMRT, respectively. However, estimated LARs for bladder cancer, more than 25 cm from the field edge for the same patient and treatment field, were estimated to be 0.2% and 0.02% from IMRT and proton therapy, respectively. Risks for proton beam scanning was found to be an order of magnitude smaller compared to passive proton therapy. Conclusion In terms of out-of-field risks, IMRT offers advantage close to the primary field and an increasing advantage for passive proton therapy is noticed with increasing distance to the field. Scanning proton beam therapy shows the lowest risks. PMID:21159398

  6. Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular-scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS).

    PubMed

    Chandra, S; Ahmad, T; Barth, R F; Kabalka, G W

    2014-06-01

    Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron-10 ((10)B) atoms to individual tumour cells. Cell killing results from the (10)B (n, α)(7) Li neutron capture and fission reactions that occur if a sufficient number of (10)B atoms are localized in the tumour cells. Intranuclear (10)B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of (10)B atoms reflects both bound and free pools of boron in individual tumour cells. The assessment of these pools, delivered by a boron delivery agent, currently cannot be made at subcellular-scale resolution by clinically applicable techniques such as positron emission tomography and magnetic resonance imaging. In this study, a secondary ion mass spectrometry based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G glioblastoma cells were evaluated for boron uptake and retention of two delivery agents. The first, L-p-boronophenylalanine (BPA), has been used clinically for BNCT of high-grade gliomas, recurrent tumours of the head and neck region and melanomas. The second, a boron analogue of an unnatural amino acid, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC), has been studied in rodent glioma and melanoma models by quantification of boron in the nucleus and cytoplasm of individual tumour cells. The bound and free pools of boron were assessed by exposure of cells to boron-free nutrient medium. Both BPA and cis-ABCPC delivered almost 70% of the pool of boron in the free or loosely bound form to the nucleus and cytoplasm of human glioblastoma cells. This free pool of boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular boron. In the case of BPA, the intracellular free pool of boron also was affected by the presence of phenylalanine in the nutrient medium. This

  7. 3D for the people: multi-camera motion capture in the field with consumer-grade cameras and open source software

    PubMed Central

    Evangelista, Dennis J.; Ray, Dylan D.; Hedrick, Tyson L.

    2016-01-01

    ABSTRACT Ecological, behavioral and biomechanical studies often need to quantify animal movement and behavior in three dimensions. In laboratory studies, a common tool to accomplish these measurements is the use of multiple, calibrated high-speed cameras. Until very recently, the complexity, weight and cost of such cameras have made their deployment in field situations risky; furthermore, such cameras are not affordable to many researchers. Here, we show how inexpensive, consumer-grade cameras can adequately accomplish these measurements both within the laboratory and in the field. Combined with our methods and open source software, the availability of inexpensive, portable and rugged cameras will open up new areas of biological study by providing precise 3D tracking and quantification of animal and human movement to researchers in a wide variety of field and laboratory contexts. PMID:27444791

  8. 3D for the people: multi-camera motion capture in the field with consumer-grade cameras and open source software.

    PubMed

    Jackson, Brandon E; Evangelista, Dennis J; Ray, Dylan D; Hedrick, Tyson L

    2016-09-15

    Ecological, behavioral and biomechanical studies often need to quantify animal movement and behavior in three dimensions. In laboratory studies, a common tool to accomplish these measurements is the use of multiple, calibrated high-speed cameras. Until very recently, the complexity, weight and cost of such cameras have made their deployment in field situations risky; furthermore, such cameras are not affordable to many researchers. Here, we show how inexpensive, consumer-grade cameras can adequately accomplish these measurements both within the laboratory and in the field. Combined with our methods and open source software, the availability of inexpensive, portable and rugged cameras will open up new areas of biological study by providing precise 3D tracking and quantification of animal and human movement to researchers in a wide variety of field and laboratory contexts.

  9. Low-Dose-Area-Constrained Helical TomoTherapy-Based Whole Breast Radiotherapy and Dosimetric Comparison with Tangential Field-in-Field IMRT

    PubMed Central

    Qiu, Jie; Yang, Bo; Hou, Xiaorong; Zhang, Fuquan

    2013-01-01

    Background and Purpose. To present a novel helical TomoTherapy-based method for whole breast radiotherapy that has better dosimetry and also has acceptable low-dose regions for lungs, heart, and contralateral breast compared with tangential field-in-field IMRT (FIF-IMRT). Material and Methods. Ten patients with left-side breast cancer were planned with low-dose-area-constrained helical TomoTherapy (LDC-HT) and FIF-IMRT. Dosimetry was compared for all techniques. Results. Coverage of the whole breast was adequate with both techniques. Homogeneity index (HI) and conformity index (CI) were better with LDC-HT. LDC-HT showed dosimetry advantages over FIF-IMRT for ipsilateral lung and heart in not only high-dose levels but also in low-dose levels such as V10 Gy and V5 Gy. For contralateral lung, both techniques can provide good protection, although the mean dose of LDC-HT is higher than that of FIF-IMRT. Conclusions. With LDC-HT, we obtained adequate target coverage, better HI and CI of target volume, better sparing of organs at risk, and acceptably low-dose areas compared with FIF-IMRT. LDC-HT could be a feasible method in whole breast radiotherapy. Clinical benefits of LDC-HT need further investigation. PMID:24024197

  10. The GEANT4 toolkit capability in the hadron therapy field: simulation of a transport beam line

    NASA Astrophysics Data System (ADS)

    Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.; Raffaele, L.; Russo, G.; Guatelli, S.; Pia, M. G.

    2006-01-01

    At Laboratori Nazionali del Sud of the Instituto Nazionale di Fisica Nucleare of Catania (Sicily, Italy), the first Italian hadron therapy facility named CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) has been realized. Inside CATANA 62 MeV proton beams, accelerated by a superconducting cyclotron, are used for the radiotherapeutic treatments of some types of ocular tumours. Therapy with hadron beams still represents a pioneer technique, and only a few centers worldwide can provide this advanced specialized cancer treatment. On the basis of the experience so far gained, and considering the future hadron-therapy facilities to be developed (Rinecker, Munich Germany, Heidelberg/GSI, Darmstadt, Germany, PSI Villigen, Switzerland, CNAO, Pavia, Italy, Centro di Adroterapia, Catania, Italy) we decided to develop a Monte Carlo application based on the GEANT4 toolkit, for the design, the realization and the optimization of a proton-therapy beam line. Another feature of our project is to provide a general tool able to study the interactions of hadrons with the human tissue and to test the analytical-based treatment planning systems actually used in the routine practice. All the typical elements of a hadron-therapy line, such as diffusers, range shifters, collimators and detectors were modelled. In particular, we simulated the Markus type ionization chamber and a Gaf Chromic film as dosimeters to reconstruct the depth (Bragg peak and Spread Out Bragg Peak) and lateral dose distributions, respectively. We validated our simulated detectors comparing the results with the experimental data available in our facility.

  11. Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.

    PubMed

    Giladi, Moshe; Weinberg, Uri; Schneiderman, Rosa S; Porat, Yaara; Munster, Michal; Voloshin, Tali; Blatt, Roni; Cahal, Shay; Itzhaki, Aviran; Onn, Amir; Kirson, Eilon D; Palti, Yoram

    2014-10-01

    Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Common treatment modalities for NSCLC include surgery, radiotherapy, chemotherapy, and, in recent years, the clinical management paradigm has evolved with the advent of targeted therapies. Despite such advances, the impact of systemic therapies for advanced disease remains modest, and as such, the prognosis for patients with NSCLC remains poor. Standard modalities are not without their respective toxicities and there is a clear need to improve both efficacy and safety for current management approaches. Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death. We evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. We investigated the response of Lewis lung carcinoma and KLN205 squamous cell carcinoma in mice treated with TTFields in combination with pemetrexed, cisplatin, or paclitaxel and compared these to the efficacy observed in mice exposed only to the single agents. Combining TTFields with these therapeutic agents enhanced treatment efficacy in comparison with the respective single agents and control groups in all animal models. Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC.

  12. "We Do Not See Things as They Are. We See Things as We Are." Capturing the Transformation of Career Changing Women from STEM Fields to Teaching

    ERIC Educational Resources Information Center

    Snyder, Catherine

    2010-01-01

    This qualitative study tracks the journeys of four career changing women in STEM fields as they pursue a Master of Arts in Teaching degree and transition into teaching positions. Through analysis of archived writing, journaling, photo elicitation, interviews and member-checking, the study analyzes participants' thinking and learning at the…

  13. [Physiotherapy with rotating pulse magnetic field in combined therapy of chronic obstructive pulmonary disease].

    PubMed

    Lobanov, A Iu; Gilinskaia, N Iu; Chereĭskaia, N K

    2005-01-01

    Rationale and technique are proposed and clinical trial has been made of efficacy of chronic obstructive pulmonary disease (COPD) treatment with impacts of rotating impulse magnetic field (RIMF) from the device Polyus-VIEM (two fields, induction 48-72 mTe, reversive rotation, 4-6 s reversion duration, 20-30 Hz, 7-10 min exposure of each field, 7-10 procedures). The addition of RIMF in combined treatment of COPD improves treatment and shortens its duration.

  14. Testing the Capture Magnet

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image of a model capture magnet was taken after an experiment in a Mars simulation chamber at the University of Aarhus, Denmark. It has some dust on it, but not as much as that on the Mars Exploration Rover Spirit's capture magnet. The capture and filter magnets on both Mars Exploration Rovers were delivered by the magnetic properties team at the Center for Planetary Science, Copenhagen, Denmark.

  15. A phenomenological relative biological effectiveness approach for proton therapy based on an improved description of the mixed radiation field

    NASA Astrophysics Data System (ADS)

    Mairani, A.; Dokic, I.; Magro, G.; Tessonnier, T.; Bauer, J.; Böhlen, T. T.; Ciocca, M.; Ferrari, A.; Sala, P. R.; Jäkel, O.; Debus, J.; Haberer, T.; Abdollahi, A.; Parodi, K.

    2017-02-01

    Proton therapy treatment planning systems (TPSs) are based on the assumption of a constant relative biological effectiveness (RBE) of 1.1 without taking into account the found in vitro experimental variations of the RBE as a function of tissue type, linear energy transfer (LET) and dose. The phenomenological RBE models available in literature are based on the dose-averaged LET (LET D ) as an indicator of the physical properties of the proton radiation field. The LET D values are typically calculated taking into account primary and secondary protons, neglecting the biological effect of heavier secondaries. In this work, we have introduced a phenomenological RBE approach which considers the biological effect of primary protons, and of secondary protons, deuterons, tritons (Z  =  1) and He fragments (3He and 4He, Z  =  2). The calculation framework, coupled with a Monte Carlo (MC) code, has been successfully benchmarked against clonogenic in vitro data measured in this work for two cell lines and then applied to determine biological quantities for spread-out Bragg peaks and a prostate and a head case. The introduced RBE formalism, which depends on the mixed radiation field, the dose and the ratio of the linear–quadratic model parameters for the reference radiation {{≤ft(α /β \\right)}\\text{ph}} , predicts, when integrated in an MC code, higher RBE values in comparison to LET D -based parameterizations. This effect is particular enhanced in the entrance channel of the proton field and for low {{≤ft(α /β \\right)}\\text{ph}} tissues. For the prostate and the head case, we found higher RBE-weighted dose values up to about 5% in the entrance channel when including or neglecting the Z  =  2 secondaries in the RBE calculation. TPSs able to proper account for the mixed radiation field in proton therapy are thus recommended for an accurate determination of the RBE in the whole treatment field.

  16. Magnetic nanoparticles with high specific absorption rate of electromagnetic energy at low field strength for hyperthermia therapy.

    PubMed

    Shubitidze, Fridon; Kekalo, Katsiaryna; Stigliano, Robert; Baker, Ian

    2015-03-07

    Magnetic nanoparticles (MNPs), referred to as the Dartmouth MNPs, which exhibit high specific absorption rate at low applied field strength have been developed for hyperthermia therapy applications. The MNPs consist of small (2-5 nm) single crystals of gamma-Fe2O3 with saccharide chains implanted in their crystalline structure, forming 20-40 nm flower-like aggregates with a hydrodynamic diameter of 110-120 nm. The MNPs form stable (>12 months) colloidal solutions in water and exhibit no hysteresis under an applied quasistatic magnetic field, and produce a significant amount of heat at field strengths as low as 100 Oe at 99-164 kHz. The MNP heating mechanisms under an alternating magnetic field (AMF) are discussed and analyzed quantitatively based on (a) the calculated multi-scale MNP interactions obtained using a three dimensional numerical model called the method of auxiliary sources, (b) measured MNP frequency spectra, and (c) quantified MNP friction losses based on magneto-viscous theory. The frequency responses and hysteresis curves of the Dartmouth MNPs are measured and compared to the modeled data. The specific absorption rate of the particles is measured at various AMF strengths and frequencies, and compared to commercially available MNPs. The comparisons demonstrate the superior heating properties of the Dartmouth MNPs at low field strengths (<250 Oe). This may extend MNP hyperthermia therapy to deeper tumors that were previously non-viable targets, potentially enabling the treatment of some of the most difficult cancers, such as pancreatic and rectal cancers, without damaging normal tissue.

  17. Magnetic nanoparticles with high specific absorption rate of electromagnetic energy at low field strength for hyperthermia therapy

    NASA Astrophysics Data System (ADS)

    Shubitidze, Fridon; Kekalo, Katsiaryna; Stigliano, Robert; Baker, Ian

    2015-03-01

    Magnetic nanoparticles (MNPs), referred to as the Dartmouth MNPs, which exhibit high specific absorption rate at low applied field strength have been developed for hyperthermia therapy applications. The MNPs consist of small (2-5 nm) single crystals of gamma-Fe2O3 with saccharide chains implanted in their crystalline structure, forming 20-40 nm flower-like aggregates with a hydrodynamic diameter of 110-120 nm. The MNPs form stable (>12 months) colloidal solutions in water and exhibit no hysteresis under an applied quasistatic magnetic field, and produce a significant amount of heat at field strengths as low as 100 Oe at 99-164 kHz. The MNP heating mechanisms under an alternating magnetic field (AMF) are discussed and analyzed quantitatively based on (a) the calculated multi-scale MNP interactions obtained using a three dimensional numerical model called the method of auxiliary sources, (b) measured MNP frequency spectra, and (c) quantified MNP friction losses based on magneto-viscous theory. The frequency responses and hysteresis curves of the Dartmouth MNPs are measured and compared to the modeled data. The specific absorption rate of the particles is measured at various AMF strengths and frequencies, and compared to commercially available MNPs. The comparisons demonstrate the superior heating properties of the Dartmouth MNPs at low