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Sample records for neutron capture therapies

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  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. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  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. 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.

  20. 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.

  1. 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.

  2. 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.

  3. [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.

  4. 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.}

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Neutron sources for a neutron capture therapy facility

    SciTech Connect

    Lennox, A.J.

    1993-04-01

    Recent advances in the development of boron pharmaceuticals have reopened the possibility of using epithermal neutrons to treat brain tumors containing boron-10. This paper summarizes the approaches being used to generate the neutron sources and identifies specific areas where more research and development are needed.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  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. 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.

  19. 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.

  20. 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.

  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. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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)

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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].

  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. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Neutron therapy of cancer

    NASA Technical Reports Server (NTRS)

    Frigerio, N. A.; Nellans, H. N.; Shaw, M. J.

    1969-01-01

    Reports relate applications of neutrons to the problem of cancer therapy. The biochemical and biophysical aspects of fast-neutron therapy, neutron-capture and neutron-conversion therapy with intermediate-range neutrons are presented. Also included is a computer program for neutron-gamma radiobiology.

  14. 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)

  15. (A clinical trial of neutron capture therapy for brain tumors)

    SciTech Connect

    Zamenhof, R.G.

    1988-01-01

    This report describes progress made in refining of neutron-induced alpha tract autoradiography, in designing epithermal neutron bean at MITR-II and in planning treatment dosimetry using Monte Carlo techniques.

  16. 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.

  17. 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.

  18. 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.

  19. 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).

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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].

  12. [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.

  13. (A clinical trial of neutron capture therapy for brain tumors)

    SciTech Connect

    Zamenhof, R.G.

    1990-01-01

    This document briefly describes recent advances in the author's laboratory. Topics described include neutron beam design, high- resolution autoradiography, boronated phenylalanine (BPA) distribution and survival studies in glioma bearing mice, computer- aided treatment planning, prompt gamma boron 10 analysis facility at MITI-II, non-rodent BPA toxicity studies, and preparations for clinical studies.

  14. (A clinical trial of neutron capture therapy for brain tumors)

    SciTech Connect

    Zamenhof, R.G.

    1989-01-01

    This report describes accomplishments by this laboratory concerning development of high-resolution alpha-autoradiography design of an optimized epithermal neutron beam dosimetry and treatment planning Using Monte Carlo techniques development of a prompt-gamma {sup 10}B analysis facility.

  15. 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.

  16. [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.

  17. 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

  18. 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.

  19. 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.

  20. 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)).

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  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. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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).

  15. 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.

  16. 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.

  17. 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.

  18. [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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Evaluation of an iron-filtered epithermal neutron beam for neutron-capture therapy.

    PubMed

    Musolino, S V; McGinley, P H; Greenwood, R C; Kliauga, P; Fairchild, R G

    1991-01-01

    An epithermal neutron filter using iron, aluminum, and sulfur was evaluated to determine if the therapeutic performance could be improved with respect to aluminum-sulfur-based filters. An empirically optimized filter was developed that delivered a 93% pure beam of 24-keV epithermal neutrons. It was expected that a thick filter using iron with a density thickness greater than 200 g/cm2 would eliminate the excess gamma contamination found in Al-S filters. This research showed that prompt gamma production from neutron interactions in iron was the dominant dose component. Dosimetric parameters of the beam were determined from the measurement of absorbed dose in air, thermal neutron flux in a head phantom, neutron and gamma spectroscopy, and microdosimetry.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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)

  16. 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.

  17. 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.

  18. 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.

  19. 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

  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. 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.

  2. 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.

  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. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  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. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Neutron capture reactions at DANCE

    NASA Astrophysics Data System (ADS)

    Bredeweg, T. A.

    2008-05-01

    The Detector for Advanced Neutron Capture Experiments (DANCE) is a 4π BaF2 array consisting of 160 active detector elements. The primary purpose of the array is to perform neutron capture cross section measurements on small (>~100 μg) and/or radioactive (<~100 mCi) species. The measurements made possible with this array will be useful in answering outstanding questions in the areas of national security, threat reduction, nuclear astrophysics, advanced reactor design and accelerator transmutation of waste. Since the commissioning of DANCE we have performed neutron capture cross section measurements on a wide array of medium to heavy mass nuclides. Measurements to date include neutron capture cross sections on 241,243Am, neutron capture and neutron-induced fission cross sections and capture-to-fission ratio (α = σγ/σf) for 235U using a new fission-tagging detector as well as neutron capture cross sections for several astrophysics branch-point nuclei. Results from several of these measurements will be presented along with a discussion of additional physics information that can be extracted from the DANCE data.

  4. Neutron capture reactions at DANCE

    SciTech Connect

    Bredeweg, T. A.

    2008-05-12

    The Detector for Advanced Neutron Capture Experiments (DANCE) is a 4{pi} BaF{sub 2} array consisting of 160 active detector elements. The primary purpose of the array is to perform neutron capture cross section measurements on small (> or approx.100 {mu}g) and/or radioactive (< or approx. 100 mCi) species. The measurements made possible with this array will be useful in answering outstanding questions in the areas of national security, threat reduction, nuclear astrophysics, advanced reactor design and accelerator transmutation of waste. Since the commissioning of DANCE we have performed neutron capture cross section measurements on a wide array of medium to heavy mass nuclides. Measurements to date include neutron capture cross sections on {sup 241,243}Am, neutron capture and neutron-induced fission cross sections and capture-to-fission ratio ({alpha} = {sigma}{sub {gamma}}/{sigma}{sub f}) for {sup 235}U using a new fission-tagging detector as well as neutron capture cross sections for several astrophysics branch-point nuclei. Results from several of these measurements will be presented along with a discussion of additional physics information that can be extracted from the DANCE data.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. [A clinical trial of neutron capture therapy for brain tumors]. Technical progress report 1988

    SciTech Connect

    Zamenhof, R.G.

    1988-12-31

    This report describes progress made in refining of neutron-induced alpha tract autoradiography, in designing epithermal neutron bean at MITR-II and in planning treatment dosimetry using Monte Carlo techniques.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

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

    SciTech Connect

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

    1990-09-01

    This monthly bulletin describes activities in the following project areas during this reporting period: supporting technology development, large animal model studies, neutron source and facility preparation, administration and common support, and PBF operations. (FI)

  3. 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.

  4. 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.

  5. Design of multidirectional neutron beams for boron neutron capture synovectomy

    SciTech Connect

    Gierga, D.P.; Yanch, J.C.; Shefer, R.E.

    1997-12-01

    Boron neutron capture synovectomy (BNCS) is a potential application of the {sup 10}B(n, a) {sup 7}Li reaction for the treatment of rheumatoid arthritis. The target of therapy is the synovial membrane. Rheumatoid synovium is greatly inflamed and is the source of the discomfort and disability associated with the disease. The BNCS proposes to destroy the synovium by first injecting a boron-labeled compound into the joint space and then irradiating the joint with a neutron beam. This study discusses the design of a multidirectional neutron beam for BNCS.

  6. [A clinical trial of neutron capture therapy for brain tumors]. Technical progress report, 1990

    SciTech Connect

    Zamenhof, R.G.

    1990-12-31

    This document briefly describes recent advances in the author`s laboratory. Topics described include neutron beam design, high- resolution autoradiography, boronated phenylalanine (BPA) distribution and survival studies in glioma bearing mice, computer- aided treatment planning, prompt gamma boron 10 analysis facility at MITI-II, non-rodent BPA toxicity studies, and preparations for clinical studies.

  7. [A clinical trial of neutron capture therapy for brain tumors]. Technical progress report 1989

    SciTech Connect

    Zamenhof, R.G.

    1989-12-31

    This report describes accomplishments by this laboratory concerning development of high-resolution alpha-autoradiography design of an optimized epithermal neutron beam dosimetry and treatment planning Using Monte Carlo techniques development of a prompt-gamma {sup 10}B analysis facility.

  8. Capturing the Future: Direct and Indirect Probes of Neutron Capture

    SciTech Connect

    Couture, Aaron Joseph

    2016-08-31

    This report documents aspects of direct and indirect neutron capture. The importance of neutron capture rates and methods to determine them are presented. The following conclusions are drawn: direct neutron capture measurements remain a backbone of experimental study; work is being done to take increased advantage of indirect methods for neutron capture; both instrumentation and facilities are making new measurements possible; more work is needed on the nuclear theory side to understand what is needed furthest from stability.

  9. 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

  10. 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.

  11. Correlation of clinical outcome to the estimated radiation dose from Boron Neutron Capture Therapy (BNCT)

    SciTech Connect

    Chadha, M.; Coderre, J.A.; Chanana, A.D.

    1996-12-31

    A phase I/II trial delivering a single fraction of BNCT using p-Boronophenylalanine-Fructose and epithermal neutrons at the the Brookhaven Medical Research Reactor was initiated in September 1994. The primary endpiont of the study was to evaluate the feasibility and safety of a given BNCT dose. The clinical outcome of the disease was a secondary endpoint of the study. The objective of this paper is to evaluate the correlation of the clinical outcome of patients to the estimated radiation dose from BNCT.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Development of beryllium-based neutron target system with three-layer structure for accelerator-based neutron source for boron neutron capture therapy.

    PubMed

    Kumada, Hiroaki; Kurihara, Toshikazu; Yoshioka, Masakazu; Kobayashi, Hitoshi; Matsumoto, Hiroshi; Sugano, Tomei; Sakurai, Hideyuki; Sakae, Takeji; Matsumura, Akira

    2015-12-01

    The iBNCT project team with University of Tsukuba is developing an accelerator-based neutron source. Regarding neutron target material, our project has applied beryllium. To deal with large heat load and blistering of the target system, we developed a three-layer structure for the target system that includes a blistering mitigation material between the beryllium used as the neutron generator and the copper heat sink. The three materials were bonded through diffusion bonding using a hot isostatic pressing method. Based on several verifications, our project chose palladium as the intermediate layer. A prototype of the neutron target system was produced. We will verify that sufficient neutrons for BNCT treatment are generated by the device in the near future.

  11. 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.

  12. 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).

  13. 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.

  14. 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.

  15. 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.

  16. Benchmarking a surrogate reaction for neutron capture

    SciTech Connect

    Hatarik, R.; Cizewski, J. A.; Hatarik, A. M.; O'Malley, P. D.; Bernstein, L. A.; Bleuel, D. L.; Burke, J. T.; Escher, J. E.; Lesher, S. R.; Gibelin, J.; Phair, L.; Rodriguez-Vieitez, E.; Goldblum, B. L.; Swan, T.; Wiedeking, M.

    2010-01-15

    {sup 171,173}Yb(d,p{gamma}) reactions are measured, with the goal of extracting the neutron capture cross-section ratio as a function of the neutron energy using the external surrogate ratio method. The cross-section ratios obtained are compared to the known neutron capture cross sections. Although the Weisskopf-Ewing limit is demonstrated not to apply for these low neutron energies, a prescription for deducing surrogate cross sections is presented. The surrogate cross-section ratios deduced from the {sup 171,173}Yb(d,p{gamma}) measurements agree with the neutron capture results within 15%.

  17. 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.

  18. 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.

  19. 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.

  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. 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.

  5. Neutronic effects on tungsten-186 double neutron capture

    NASA Astrophysics Data System (ADS)

    Garland, Marc Alan

    Rhenium-188, a daughter product of tungsten-188, is an isotope of great interest in therapeutic nuclear medicine, being used in dozens of laboratory and clinical investigations worldwide. Applications include various cancer therapy strategies, treatment of rheumatoid arthritis, prevention of restenosis following coronary artery angioplasty, and palliation of bone pain associated with cancer metastases. With its half-life of 17 hours, 2.12 MeV (maximum) beta-particle emission, chemical similarity to technetium-99m (the most widely used diagnostic radioisotope), and its availability in a convenient tungsten-188/rhenium-188 generator system, rhenium-188 is a superb candidate for a broad range of applications. Production of 188W is typically via double neutron capture by 186W in a high flux nuclear reactor, predominantly the High Flux Isotope Reactor at the Oak Ridge National Laboratory in Tennessee. Experience at HFIR has shown that production yields (measured in Ci of 188W produced per g of 186W target) decrease considerably as target size increases. While the phenomenon of neutron resonance self-shielding would be expected to produce such an effect, temperature effects on neutron flux distribution and neutron capture rates may also be involved. Experimental investigations of these phenomena have not been previously performed. The work presented in this thesis evaluates the factors that contribute to the decrease in 188W yield from both theoretical and experimental standpoints. Neutron self-shielding and temperature effects were characterized to develop a strategy for target design that would optimize production yield, an important factor in minimizing health care costs. It was determined that decrease in yield due to neutron self-shielding can be attributed to depletion of epithermal neutrons at resonant energies, most significantly within the initial 0.4 mm depth of the target. The results from these studies further show that 188W yield in the interior of the

  6. 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.

  7. Neutron captures and the r-process

    SciTech Connect

    Farouqi, K.; Kratz, K.-L.; Pfeiffer, B.; Rauscher, T.; Thielemann, F.-K.

    2006-03-13

    In order to study possible neutron-capture effects during an r-process, it is necessary to perform fully dynamical simulations. We have performed such calculations within the model of an adiabatically expanding high-entropy bubble of a SN II, using temperature-dependent reaction rates including the NON-SMOKER neutron-capture rates of Rauscher et al.

  8. 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.

  9. Measurement of neutron capture on 136Xe

    NASA Astrophysics Data System (ADS)

    Albert, J. B.; Daugherty, S. J.; Johnson, T. N.; O'Conner, T.; Kaufman, L. J.; Couture, A.; Ullmann, J. L.; Krtička, M.

    2016-09-01

    136Xe is a 0 ν β β decay candidate isotope, and is used in multiple experiments searching for this hypothetical decay mode. These experiments require precise information about neutron capture for their background characterization and minimization. Thermal and resonant neutron capture on 136Xe have been measured at the Detector for Advanced Neutron Capture Experiments (DANCE) at the Los Alamos Neutron Science Center. A neutron beam ranging from thermal energy to greater than 100 keV was incident on a gas cell filled with isotopically pure 136Xe. The relative neutron capture cross sections for neutrons at thermal energies and the first resonance at 2.154 keV have been measured, yielding a new absolute measurement of 0.238 ±0.019 b for the thermal neutron capture cross section. Additionally, the γ cascades for captures at both energies have been measured, and cascade models have been developed which may be used by 0 ν β β experiments using 136Xe.

  10. Capture-Gated Fast Neutron Spectroscopy

    NASA Astrophysics Data System (ADS)

    Mumm, H. P.; Abdurashitov, J. N.; Beise, E. J.; Breuer, H.; Gavrin, V. N.; Heimbach, C. R.; Langford, T. J.; Mendenhall, M.; Nico, J. S.; Shikhin, A. A.

    2015-10-01

    We present recent developments in fast neutron detection using segmented spectrometers based on the principle of capture-gating. Our approach employs an organic scintillator to detect fast neutrons through their recoil interaction with protons in the scintillator. The neutrons that thermalize and are captured produce a signal indicating that the event was due to a neutron recoil and that the full energy of the neutron was deposited. The delayed neutron capture also serves to discriminate against uncorrelated background events. The segmentation permits reconstruction of the initial neutron energy despite the nonlinear response of the scintillator. We have constructed spectrometers using both He-3 proportional counters and Li-6 doping as capture agents in plastic and liquid organic scintillators. We discuss the operation of the spectrometers for the measurement of low levels of fast neutrons for several applications, including the detection of very low-activity neutron sources and the characterization of the flux and spectrum of fast neutrons at the Earth's surface and in the underground environment.

  11. Moderated 252Cf neutron energy spectra in brain tissue and calculated boron neutron capture dose.

    PubMed

    Rivard, Mark J; Zamenhof, Robert G

    2004-11-01

    While there is significant clinical experience using both low- and high-dose (252)Cf brachytherapy, combination therapy using (10)B for neutron capture therapy-enhanced (252)Cf brachytherapy has not been performed. Monte Carlo calculations were performed in a brain phantom (ICRU 44 brain tissue) to evaluate the dose enhancement predicted for a range of (10)B concentrations over a range of distances from a clinical (252)Cf source. These results were compared to experimental measurements and calculations published in the literature. For (10)B concentrations neutron capture dose enhancement was small in comparison to the (252)Cf fast neutron dose.

  12. "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).

  13. 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.

  14. 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.

  15. 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.

  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. 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.

  18. Neutron capture in the r-process

    SciTech Connect

    Surman, Rebecca; Mclaughlin, Gail C; Mumpower, Matthew; Hix, William Raphael; Jones, K. L.

    2010-01-01

    Recently we have shown that neutron capture rates on nuclei near stability significantly influence the r-process abundance pattern. We discuss the different mechanisms by which the abundance pattern is sensitive to the capture rates and identify key nuclei whose rates are of particular im- portance. Here we consider nuclei in the A = 130 and A = 80 regions.

  19. Chandra Captures Neutron Star Action

    NASA Video Gallery

    This movie from NASA's Chandra X-ray Observatory shows a fast moving jet of particles produced by a rapidly rotating neutron star, and may provide new insight into the nature of some of the densest...

  20. High-power electron beam tests of a liquid-lithium target and characterization study of (7)Li(p,n) near-threshold neutrons for accelerator-based boron neutron capture therapy.

    PubMed

    Halfon, S; Paul, M; Arenshtam, A; Berkovits, D; Cohen, D; Eliyahu, I; Kijel, D; Mardor, I; Silverman, I

    2014-06-01

    A compact Liquid-Lithium Target (LiLiT) was built and tested with a high-power electron gun at Soreq Nuclear Research Center (SNRC). The target is intended to demonstrate liquid-lithium target capabilities to constitute an accelerator-based intense neutron source for Boron Neutron Capture Therapy (BNCT) in hospitals. The lithium target will produce neutrons through the (7)Li(p,n)(7)Be reaction and it will overcome the major problem of removing the thermal power >5kW generated by high-intensity proton beams, necessary for sufficient therapeutic neutron flux. In preliminary experiments liquid lithium was flown through the target loop and generated a stable jet on the concave supporting wall. Electron beam irradiation demonstrated that the liquid-lithium target can dissipate electron power densities of more than 4kW/cm(2) and volumetric power density around 2MW/cm(3) at a lithium flow of ~4m/s, while maintaining stable temperature and vacuum conditions. These power densities correspond to a narrow (σ=~2mm) 1.91MeV, 3mA proton beam. A high-intensity proton beam irradiation (1.91-2.5MeV, 2mA) is being commissioned at the SARAF (Soreq Applied Research Accelerator Facility) superconducting linear accelerator. In order to determine the conditions of LiLiT proton irradiation for BNCT and to tailor the neutron energy spectrum, a characterization of near threshold (~1.91MeV) (7)Li(p,n) neutrons is in progress based on Monte-Carlo (MCNP and Geant4) simulation and on low-intensity experiments with solid LiF targets. In-phantom dosimetry measurements are performed using special designed dosimeters based on CR-39 track detectors.

  1. Neutron capture by hook or by crook

    NASA Astrophysics Data System (ADS)

    Mosby, Shea

    2016-03-01

    The neutron capture reaction is a topic of fundamental interest for both heavy element (A>60) nucleosynthesis and applications in such fields as nuclear energy and defense. The full suite of interesting isotopes ranges from stable nuclei to the most exotic, and it is not possible to directly measure all the relevant reaction rates. The DANCE instrument at Los Alamos provides direct access to the neutron capture reaction for stable and long-lived nuclei, while Apollo coupled to HELIOS at Argonne has been developed as an indirect probe for cases where a direct measurement is impossible. The basic techniques and their implications will be presented, and the status of ongoing experimental campaigns to address neutron capture in the A=60 and A=100 mass regions will be discussed.

  2. Optimum design of a moderator system based on dose calculation for an accelerator driven Boron Neutron Capture Therapy.

    PubMed

    Inoue, R; Hiraga, F; Kiyanagi, Y

    2014-06-01

    An accelerator based BNCT has been desired because of its therapeutic convenience. However, optimal design of a neutron moderator system is still one of the issues. Therefore, detailed studies on materials consisting of the moderator system are necessary to obtain the optimal condition. In this study, the epithermal neutron flux and the RBE dose have been calculated as the indicators to look for optimal materials for the filter and the moderator. As a result, it was found that a combination of MgF2 moderator with Fe filter gave best performance, and the moderator system gave a dose ratio greater than 3 and an epithermal neutron flux over 1.0×10(9)cm(-2)s(-1).

  3. Collaborative Physical and Biological Dosimetry Studies for Neutron Capture Therapy at the RA-1 Research Reactor Facility

    SciTech Connect

    Nigg, D.W.; Schwint, A.E.; Hartwell, J.K.; Heber, E.M.; Trivillin, V.; Castillo, J.; Wentzeis, L.; Sloan, P.; Wemple, C.A.

    2004-10-04

    Initial physical dosimetry measurements have been completed using activation spectrometry and thermoluminiscent dosimeters to characterize the BNCT irradiation facility developed at the RA-1 research reactor operated by the Argentine National Atomic Energy Commission in Buenos Aires. Some biological scoping irradiations have also been completed using a small-animal (hamster) oral mucosa tumor model. Results indicate that the RA-1 neutron source produces useful dose rates but that some improvements in the initial configuration will be needed to optimize the spectrum for thermal-neutron BNCT research applications.

  4. Collaborative Physical and Biological Dosimetry Studies for Neutron Capture Therapy at the RA-1 Research Reactor Facility

    SciTech Connect

    David W. Nigg; Amanda E. Schwint; John K. Hartwell; Elisa M. Heber; Veronica Trivillin; Jorge Castillo; Luis Wentzeis; Patrick Sloan; Charles A. Wemple

    2004-10-01

    Initial physical dosimetry measurements have been completed using activation spectrometry and thermoluminiscent dosimeters to characterize the BNCT irradiation facility developed at the RA-1 research reactor operated by the Argentine National Atomic Energy Commission in Buenos Aires. Some biological scoping irradiations have also been completed using a small-animal (hamster) oral mucosa tumor model. Results indicate that the RA-1 neutron source produces useful dose rates but that some improvements in the initial configuration will be needed to optimize the spectrum for thermal-neutron BNCT research applications.

  5. Neutron capture cross section of Am241

    NASA Astrophysics Data System (ADS)

    Jandel, M.; Bredeweg, T. A.; Bond, E. M.; Chadwick, M. B.; Clement, R. R.; Couture, A.; O'Donnell, J. M.; Haight, R. C.; Kawano, T.; Reifarth, R.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wilhelmy, J. B.; Wouters, J. M.; Agvaanluvsan, U.; Parker, W. E.; Wu, C. Y.; Becker, J. A.

    2008-09-01

    The neutron capture cross section of Am241 for incident neutrons from 0.02 eV to 320 keV has been measured with the detector for advanced neutron capture experiments (DANCE) at the Los Alamos Neutron Science Center. The thermal neutron capture cross section was determined to be 665±33 b. Our result is in good agreement with other recent measurements. Resonance parameters for En<12 eV were obtained using an R-matrix fit to the measured cross section. The results are compared with values from the ENDF/B-VII.0, Mughabghab, JENDL-3.3, and JEFF-3.1 evaluations. Γn neutron widths for the first three resonances are systematically larger by 5-15% than the ENDF/B-VII.0 values. The resonance integral above 0.5 eV was determined to be 1553±7 b. Cross sections in the resolved and unresolved energy regions above 12 eV were calculated using the Hauser-Feshbach theory incorporating the width-fluctuation correction of Moldauer. The calculated results agree well with the measured data, and the extracted averaged resonance parameters in the unresolved resonance region are consistent with those for the resolved resonances.

  6. Direct-Semidirect Thermal Neutron Capture Calculations

    SciTech Connect

    Arbanas, G; Dietrich, F S; Kerman, A K

    2005-12-20

    A method for computing direct-semidirect (DSD) neutron radiative capture is presented and applied to thermal neutron capture on {sup 19}F, {sup 27}Al, {sup 28,29.30}Si, {sup 35,37}Cl, {sup 39,41}K, {sup 56}Fe, and {sup 238}U, in support of data evaluation effort at the O.R.N.L. The DSD method includes both direct and semidirect capture; the latter is a core-polarization term in which the giant dipole resonance is formed. We study the effects of a commonly used ''density'' approximation to the EM operator and find it to be unsatisfactory for the nuclei considered here. We also study the magnitude of semidirect capture relative to the pure direct capture. Furthermore, we compare our results with those obtained from another direct capture code (Tedca [17]). We also compare our results with those obtained from analytical expression for external capture derived by Lane and Lynn [3], and its extension to include internal capture [7]. To estimate the effect of nuclear deformation on direct capture, we computed direct thermal capture on {sup 238}U with and without imposition of spherical symmetry. Direct capture for a spherically symmetric {sup 238}U was approximately 6 mb, while a quadrupole deformation of 0.215 on the shape of {sup 238}U lowers this cross section down to approximately 2 mb. This result suggests that effects of nuclear deformation on direct capture warrant a further study. We also find out that contribution to the direct capture on {sup 238}U from the nuclear interior significantly cancels that coming from the exterior region, and hence both contributions must be taken into account. We reproduced a well known discrepancy between the computed and observed branching ratios in {sup 56}Fe(n,{gamma}). This will lead us to revisit the concept of doorway states in the particle-hole model.

  7. Design of multivalent galactosyl carborane as a targeting specific agent for potential application to boron neutron capture therapy.

    PubMed

    Lai, Chian-Hui; Lin, Yu-Chuan; Chou, Fong-In; Liang, Chien-Fu; Lin, En-Wei; Chuang, Yung-Jen; Lin, Chun-Cheng

    2012-01-14

    A multivalent galactosyl carborane derivative 10 (dendritic glyco-borane, DGB) was synthesized and demonstrated as a potential cell-targeting agent in BNCT with HepG2 cells. DGB 10 improved the delivery of boron to HepG2 cells and neutron irradiation data show DGB 10 with ten-fold improvement at killing the HepG2 cells over BSH.

  8. 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%.

  9. 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.

  10. 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

  11. 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

  12. Performance of a New Composite Single-Crystal Filtered Thermal Neutron Beam for Neutron Capture Therapy Research at the University of Missouri

    SciTech Connect

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

    2008-11-01

    The University of Missouri (MU) Institute for Nano and Molecular Medicine, the Idaho National Laboratory (INL) and the University of Missouri Research Reactor (MURR) have undertaken a new collaborative research initiative to further the development of improved boron delivery agents for BNCT. The first step of this effort has involved the design and construction of a new thermal neutron beam irradiation facility for cell and small-animal radiobological research at the MURR. In this paper we present the beamline design with the results of pertinent neutronic design calculations. Results of neutronic performance measurements, initiated in February 2008, will also be available for inclusion in the final paper. The new beam will be located in an existing 152.4 mm (6’) diameter MURR beam tube extending from the core to the right in Figure 1. The neutron beam that emanates from the berylium reflector around the reactor is filtered with single-crystal silicon and single-crystal bismuth segments to remove high energy, fission spectrum neutrons and reactor gamma ray contamination. The irradiation chamber is downstream of the bismuth filter section, and approximately 3.95 m from the central axis of the reactor. There is sufficient neutron flux available from the MURR at its rated power of 10 MW to avoid the need for cryogenic cooling of the crystals. The MURR operates on average 150 hours per week, 52 weeks a year. In order to take advantage of 7800 hours of operation time per year the small animal BNCT facility will incorparate a shutter constucuted of boral, lead, steel and polyethylene that will allow experimenters to access the irradiation chamber a few minutes after irradiation. Independent deterministic and stochastic models of the coupled reactor core and beamline were developed using the DORT two-dimensional radiation transport code and the MCNP-5 Monte Carlo code, respectively. The BUGLE-80 47-neutron, 20-gamma group cross section library was employed for the DORT

  13. Thermal-neutron capture in light nuclei

    SciTech Connect

    Raman, S.; Jurney, E.T.; Lynn, J.E.

    1996-10-01

    We have made considerable progress toward the goal of carrying out thermal-neutron capture {gamma}-ray measurements on all stable isotopes below A=60. Information processed till now has significantly augmented the existing knowledge on the detailed nuclear level structure of many light nuclides. Most of this knowledge comes from our {gamma}-ray energies, level placements, and branching ratios of secondary transitions between low-lying states. Spectroscopic information is also contained in the cross sections of the primary transitions originating from the capturing state. This is deduced from the success of ``direct`` theories of neutron capture for many nuclides, especially those of light and near closed-shell character. 23 refs, 1 tab, 3 figs.

  14. Neutron transmission and capture of 241Am

    NASA Astrophysics Data System (ADS)

    Lampoudis, C.; Kopecky, S.; Plompen, A.; Schillebeeckx, P.; Wynants, R.; Gunsing, F.; Sage, C.; Bouland, O.; Noguere, G.

    2013-03-01

    A set of neutron transmission and capture experiments based on the Time Of Flight (TOF) technique, were performed in order to determine the 241Am capture cross section in the energy range from 0.01 eV to 1 keV. The GELINA facility of the Institute for Reference Materials and Measurements (IRMM) served as the neutron source. A pair of C6D6 liquid scintillators was used to register the prompt gamma rays emerging from the americium sample, while a Li-glass detector was used in the transmission setup. Results from the capture and transmission data acquired are consistent with each other, but appear to be inconsistent with the evaluated data files. Resonance parameters have been derived for the data up to the energy of 100 eV.

  15. 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.

  16. “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.

  17. "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.

  18. 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.

  19. Review of the fundamentals of the neutron-capture reaction

    SciTech Connect

    Chrien, R. E.

    1982-01-01

    Fifty years of research into the nature of the radiative capture reaction mechanisms is briefly summarized. A variety of such mechanisms is exploited to explain neutron capture over nine decades of neutron energy.

  20. 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.

  1. 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.

  2. Neutron capture cross section of 102Pd

    NASA Astrophysics Data System (ADS)

    Duncan, C. L.; Krane, K. S.

    2005-05-01

    The cross sections for radiative neutron capture by 102Pd have been deduced from a measurement of the γ rays emitted by 17.0-d 103Pd. The thermal cross section has been determined to be σ=1.82±0.20 b, and the effective resonance integral is I=23±4 b. We also report thermal and resonance capture cross sections for 108Pd and note possible inconsistencies with the presently accepted values of the 110Pd cross sections.

  3. Non-Statistical Effects in Neutron Capture

    NASA Astrophysics Data System (ADS)

    Koehler, P. E.; Bredeweg, T. A.; Guber, K. H.; Harvey, J. A.; O'Donnell, J. M.; Reifarth, R.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wiarda, D.; Wouters, J. M.

    2009-01-01

    There have been many reports of non-statistical effects in neutron-capture measurements. However, reports of deviations of reduced-neutron-width (Γn0) distributions from the expected Porter-Thomas (PT) shape largely have been ignored. Most of these deviations have been reported for odd-A nuclides. Because reliable spin (J) assignments have been absent for most resonances for such nuclides, it is possible that reported deviations from PT might be due to incorrect J assignments. We recently developed a new method for measuring spins of neutron resonances by using the DANCE detector at the Los Alamos Neutron Science Center (LANSCE). Measurements made with a 147Sm sample allowed us to determine spins of almost all known resonances below 1 keV. Furthermore, analysis of these data revealed that the Γn0 distribution was in good agreement with PT for resonances below 350 eV, but in disagreement with PT for resonances between 350 and 700 eV. Our previous (n,α) measurements had revealed that the α strength function also changes abruptly at this energy. There currently is no known explanation for these two non-statistical effects. Recently, we have developed another new method for determining the spins of neutron resonances. To implement this technique required a small change (to record pulse-height information for coincidence events) to a much simpler apparatus: A pair of C6D6 γ-ray detectors which we have employed for many years to measure neutron-capture cross sections at the Oak Ridge Electron Linear Accelerator (ORELA). Measurements with a 95Mo sample revealed that not only does the method work very well for determining spins, but it also makes possible parity assignments. Taken together, these new techniques at LANSCE and ORELA could be very useful for further elucidation of non-statistical effects.

  4. Non-Statistical Effects in Neutron Capture

    SciTech Connect

    Koehler, P. E.; Guber, K. H.; Harvey, J. A.; Wiarda, D.; Bredeweg, T. A.; O'Donnell, J. M.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.; Reifarth, R.

    2009-01-28

    There have been many reports of non-statistical effects in neutron-capture measurements. However, reports of deviations of reduced-neutron-width ({gamma}{sub n}{sup 0}) distributions from the expected Porter-Thomas (PT) shape largely have been ignored. Most of these deviations have been reported for odd-A nuclides. Because reliable spin (J) assignments have been absent for most resonances for such nuclides, it is possible that reported deviations from PT might be due to incorrect J assignments. We recently developed a new method for measuring spins of neutron resonances by using the DANCE detector at the Los Alamos Neutron Science Center (LANSCE). Measurements made with a {sup 147}Sm sample allowed us to determine spins of almost all known resonances below 1 keV. Furthermore, analysis of these data revealed that the {gamma}{sub n}{sup 0} distribution was in good agreement with PT for resonances below 350 eV, but in disagreement with PT for resonances between 350 and 700 eV. Our previous (n,{alpha}) measurements had revealed that the {alpha} strength function also changes abruptly at this energy. There currently is no known explanation for these two non-statistical effects. Recently, we have developed another new method for determining the spins of neutron resonances. To implement this technique required a small change (to record pulse-height information for coincidence events) to a much simpler apparatus: A pair of C{sub 6}D{sub 6}{gamma}-ray detectors which we have employed for many years to measure neutron-capture cross sections at the Oak Ridge Electron Linear Accelerator (ORELA). Measurements with a {sup 95}Mo sample revealed that not only does the method work very well for determining spins, but it also makes possible parity assignments. Taken together, these new techniques at LANSCE and ORELA could be very useful for further elucidation of non-statistical effects.

  5. Non-Statistical Effects in Neutron Capture

    SciTech Connect

    Koehler, Paul Edward; Bredeweg, t a; Guber, Klaus H; Harvey, John A; O'Donnell, J. M.; Reifarth, R.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wiarda, Dorothea; Wouters, J. M.

    2009-01-01

    There have been many reports of non-statistical effects in neutron-capture measurements. However, reports of deviations of reduced-neutron-width ({Gamma}n{sup 0}) distributions from the expected Porter-Thomas (PT) shape largely have been ignored. Most of these deviations have been reported for odd-A nuclides. Because reliable spin (J) assignments have been absent for most resonances for such nuclides, it is possible that reported deviations from PT might be due to incorrect J assignments. We recently developed a new method for measuring spins of neutron resonances by using the DANCE detector at the Los Alamos Neutron Science Center (LANSCE). Measurements made with a 147Sm sample allowed us to determine spins of almost all known resonances below 1 keV. Furthermore, analysis of these data revealed that the {Gamma}n{sup 0} distribution was in good agreement with PT for resonances below 350 eV, but in disagreement with PT for resonances between 350 and 700 eV. Our previous (n,{alpha}) measurements had revealed that the {alpha} strength function also changes abruptly at this energy. There currently is no known explanation for these two non-statistical effects. Recently, we have developed another new method for determining the spins of neutron resonances. To implement this technique required a small change (to record pulse-height information for coincidence events) to a much simpler apparatus: A pair of C6D6 ?-ray detectors which we have employed for many years to measure neutron-capture cross sections at the Oak Ridge Electron Linear Accelerator (ORELA). Measurements with a 95Mo sample revealed that not only does the method work very well for determining spins, but it also makes possible parity assignments. Taken together, these new techniques at LANSCE and ORELA could be very useful for further elucidation of non-statistical effects.

  6. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer.

    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; Trivillin, Verónica A; Schwint, Amanda E

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group

  7. 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

  8. Thermal Neutron Capture y's (CapGam)

    DOE Data Explorer

    The National Nuclear Data Center (NNDC) presents two tables showing energy and photon intensity with uncertainties of gamma rays as seen in thermal-neutron capture.  One table is organized in ascending order of gamma energy, and the second is organized by Z, A of the target. In the energy-ordered table the three strongest transitions are indicated in each case. The nuclide given is the target nucleus in the capture reaction. The gamma energies given are in keV. The gamma intensities given are relative to 100 for the strongest transition. %Iγ (per 100 n-captures) for the strongest transition is given, where known. All data are taken from the Evaluated Nuclear Structure Data File (ENSDF), a computer file of evaluated nuclear structure data and from the eXperimental Unevaluated Nuclear Data List (XUNDL). (Specialized Interface)

  9. 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

  10. 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.

  11. 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)

  12. 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.

  13. 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

  14. Neutron Capture Cross Section of 239Pu

    NASA Astrophysics Data System (ADS)

    Mosby, S.; Arnold, C.; Bredeweg, T. A.; Couture, A.; Jandel, M.; O'Donnell, J. M.; Rusev, G.; Ullmann, J. L.; Chyzh, A.; Henderson, R.; Kwan, E.; Wu, C. Y.

    2014-09-01

    The 239Pu(n,γ) cross section has been measured over the energy range 10 eV - 10 keV using the Detector for Advanced Neutron Capture Experiments (DANCE) as part of a campaign to produce precision (n,γ) measurements on 239Pu in the keV region. Fission coincidences were measured with a PPAC and used to characterize the prompt fission γ-ray spectrum in this region. The resulting spectra will be used to better characterize the fission component of another experiment with a thicker target to extend the (n,γ) cross section measurement well into the keV region.

  15. Neutron Capture Cross Section of 239Pu

    NASA Astrophysics Data System (ADS)

    Mosby, S.; Arnold, C.; Bredeweg, T. A.; Chyzh, A.; Couture, A.; Henderson, R.; Jandel, M.; Kwan, E.; O'Donnell, J. M.; Rusev, G.; Ullmann, J. L.; Wu, C. Y.

    2014-05-01

    The Detector for Advanced Neutron Capture Experiments (DANCE) has been used to measure the 239Pu(n,γ) cross section from 10 eV to the keV region. Three experimental run conditions were used to characterize the prompt fission γ-ray spectrum across the entire energy regime, measure the cross section in the resolved resonance region, and obtain necessary count rate well into the keV region. The preliminary cross sections are in good agreement with current evaluations from 10 eV to 80 keV.

  16. 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

  17. Neutron Capture Experiments on Unstable Nuclei

    SciTech Connect

    Schwantes, Jon M.; Sudowe, Ralf; Folden, Charles M., III; Nitsche, Heino; Hoffman, Darleane C.

    2005-01-15

    The overall objective of this project is the measurement of neutron capture cross sections of importance to stewardship science and astrophysical modeling of nucleosynthesis, while at the same time helping to train the next generation of scientists with expertise relevant to U.S. national nuclear security missions and to stewardship science. A primary objective of this project is to study neutron capture cross sections for various stable and unstable isotopes that will contribute to the Science Based Stockpile Stewardship (SBSS) program by providing improved data for modeling and interpretation of nuclear device performance. Much of the information obtained will also be important in astrophysical modeling of nucleosynthesis. Measurements of these neutron capture cross sections are being conducted in collaboration with researchers at the Los Alamos Neutron Science Center (LANSCE) facility using the unique Detector for Advanced Neutron Capture Experiments (DANCE). In our early discussions with the DANCE group, decisions were made on the first cross sections to be measured and how our expertise in target preparation, radiochemical separations chemistry, and data analysis could best be applied. The initial emphasis of the project was on preparing suitable targets of both natural and separated stable europium isotopes in preparation for the ultimate goal of preparing a sufficiently large target of radioactive 155Eu (t1/2 = 4.7 years) and other radioactive and stable species for neutron cross-section measurements at DANCE. Our Annual Report, ''Neutron Capture Experiments on Unstable Nuclei'' by J. M. Schwantes, R. Sudowe, C. M. Folden III, H. Nitsche, and D. C. Hoffman, submitted to NNSA in December 2003, gives details about the initial considerations and scope of the project. During the current reporting period, electroplated targets of natural Eu together with valuable, stable, and isotopically pure 151Eu and 153Eu, and isotopically separated 154Sm were measured for

  18. 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

  19. The Detector for Advanced Neutron Capture Experiments at LANSCE

    SciTech Connect

    Ullmann, J.L.; Reifarth, R.; Haight, R.C.; Hunt, L.; O'Donnell, J.M.; Rundberg, R.S.; Bredeweg, T.A.; Wilhelmy, J.B.; Fowler, M.M.; Vieira, D.J.; Wouters, J.M.; Strottman, D.D.; Kaeppeler, F.; Heil, M.; Chamberlin, E.P.

    2003-08-26

    The Detector for Advanced Neutron Capture Experiments (DANCE) is a 159-element 4{pi} barium fluoride array designed to study neutron capture on small quantities, 1 mg or less, of radioactive nuclides. It is being built on a 20 m neutron flight path which views the 'upper tier' water moderator at the Manuel J. Lujan Jr. Neutron Scattering Center at the Los Alamos Neutron Science Center. The detector design is based on Monte Carlo calculations which have suggested ways to minimize backgrounds due to neutron scattering events. A data acquisition system based on fast transient digitizers is being implemented.

  20. Neutron Capture Experiments Using the DANCE Array at Los Alamos

    NASA Astrophysics Data System (ADS)

    Dashdorj, D.; Mitchell, G. E.; Baramsai, B.; Chyzh, A.; Walker, C.; Agvaanluvsan, U.; Becker, J. A.; Parker, W.; Sleaford, B.; Wu, C. Y.; Bredeweg, T. A.; Couture, A.; Haight, R. C.; Jandel, M.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.; Krtička, M.; Bečvář, F.

    2009-03-01

    The Detector for Advanced Neutron Capture Experiments (DANCE) is designed for neutron capture measurements on very small and/or radioactive targets. The DANCE array of 160 BaF2 scintillation detectors is located at the Lujan Center at the Los Alamos Neutron Science Center (LANSCE). Accurate measurements of neutron capture data are important for many current applications as well as for basic understanding of neutron capture. The gamma rays following neutron capture reactions have been studied by the time-of-flight technique using the DANCE array. The high granularity of the array allows measurements of the gamma-ray multiplicity. The gamma-ray multiplicities and energy spectra for different multiplicities can be measured and analyzed for spin and parity determination of the resolved resonances.

  1. Neutron Capture Experiments Using the DANCE Array at Los Alamos

    SciTech Connect

    Dashdorj, D.; Mitchell, G. E.; Baramsai, B.; Chyzh, A.; Walker, C.; Agvaanluvsan, U.; Becker, J. A.; Parker, W.; Sleaford, B.; Wu, C. Y.; Bredeweg, T. A.; Couture, A.; Haight, R. C.; Jandel, M.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.; Krticka, M.; Becvar, F.

    2009-03-31

    The Detector for Advanced Neutron Capture Experiments (DANCE) is designed for neutron capture measurements on very small and/or radioactive targets. The DANCE array of 160 BaF{sub 2} scintillation detectors is located at the Lujan Center at the Los Alamos Neutron Science Center (LANSCE). Accurate measurements of neutron capture data are important for many current applications as well as for basic understanding of neutron capture. The gamma rays following neutron capture reactions have been studied by the time-of-flight technique using the DANCE array. The high granularity of the array allows measurements of the gamma-ray multiplicity. The gamma-ray multiplicities and energy spectra for different multiplicities can be measured and analyzed for spin and parity determination of the resolved resonances.

  2. Detecting energy dependent neutron capture distributions in a liquid scintillator

    NASA Astrophysics Data System (ADS)

    Balmer, Matthew J. I.; Gamage, Kelum A. A.; Taylor, Graeme C.

    2015-03-01

    A novel technique is being developed to estimate the effective dose of a neutron field based on the distribution of neutron captures in a scintillator. Using Monte Carlo techniques, a number of monoenergetic neutron source energies and locations were modelled and their neutron capture response was recorded. Using back propagation Artificial Neural Networks (ANN) the energy and incident direction of the neutron field was predicted from the distribution of neutron captures within a 6Li-loaded liquid scintillator. Using this proposed technique, the effective dose of 252Cf, 241AmBe and 241AmLi neutron fields was estimated to within 30% for four perpendicular angles in the horizontal plane. Initial theoretical investigations show that this technique holds some promise for real-time estimation of the effective dose of a neutron field.

  3. Neutron induced capture and fission discrimination using calorimetric shape decomposition

    NASA Astrophysics Data System (ADS)

    Carrapiço, C.; Berthoumieux, E.; Dridi, W.; Gonçalves, I. F.; Gunsing, F.; Lampoudis, C.; Vaz, P.; n TOF Collaboration

    2013-03-01

    The neutron capture and fission cross-sections of 233U have been measured at the neutron time-of-flight facility n_TOF at CERN in the energy range from 1 eV to 1 keV using a high performance 4π BaF2 Total Absorption Calorimeter (TAC) as a detection device. In order to separate the contributions of neutron capture and neutron induced fission in the TAC, a methodology called Calorimetric Shape Decomposition (CSD) was developed. The CSD methodology is based on the study of the TAC's energy response for all competing reactions, allowing to discriminate between γ s originating from neutron induced fission and those from neutron capture reactions without the need for fission tagging or any additional detection system. In this article, the concept behind the CSD is explained in detail together with the necessary analysis to obtain the TAC's response to neutron capture and neutron induced fission. The discrimination between capture and fission contributions is shown for several neutron energies. A comparison between the 233U neutron capture and fission yield extraction with ENDF/B-VII v1. library data is also provided.

  4. Characterization of moderator assembly dimension for accelerator boron neutron capture therapy of brain tumors using {sup 7}Li(p,n) neutrons at proton energy of 2.5 MeV

    SciTech Connect

    Tanaka, Kenichi; Kobayashi, Tooru; Bengua, Gerard; Nakagawa, Yoshinobu; Endo, Satoru; Hoshi, Masaharu

    2006-06-15

    The characteristics of moderator assembly dimension are investigated for the usage of {sup 7}Li(p,n) neutrons by 2.5 MeV protons in boron newtron capture therapy (BNCT) of brain tumors in the present study. The indexes checked are treatable protocol depth (TPD), which is the greatest depth of the region satisfying the dose requirements in BNCT protocol, proton current necessary to complete BNCT by 1 h irradiation, and the heat flux deposited in the Li target which should be removed. Assumed materials are D{sub 2}O for moderator, and mixture of polyethylene and LiF with 50 wt % for collimator. Dose distributions have been computed with MCNP 4B and 4C codes. Consequently, realized TPD does not show a monotonical tendency for the Li target diameter. However, the necessary proton current and heat flux in the Li target decreases as the Li target diameter increases, while this trend reverses at around 10 cm of the Li target diameter for the necessary proton current in the condition of this study. As to the moderator diameter, TPD does not exhibit an apparent dependence. On the other hand, necessary proton current and heat flux decrease as the moderator diameter increases, and this tendency saturates at around 60 cm of the moderator diameter in this study. As to the collimator, increase in inner diameter is suitable from the viewpoint of increasing TPD and decreasing necessary proton current and heat flux, while these indexes do not show apparent difference for collimator inner diameters over 14 cm for the parameters treated here. The practical viewpoint in selecting the parameters of moderator assembly dimension is to increase TPD, within the technically possible condition of accelerated proton current and heat removal from the Li target. In this process, the values for which the resultant characteristics mentioned above saturate or reverse would be important factors.

  5. System and method for delivery of neutron beams for medical therapy

    DOEpatents

    Nigg, D.W.; Wemple, C.A.

    1999-07-06

    A neutron delivery system that provides improved capability for tumor control during medical therapy is disclosed. The system creates a unique neutron beam that has a bimodal or multi-modal energy spectrum. This unique neutron beam can be used for fast-neutron therapy, boron neutron capture therapy (BNCT), or both. The invention includes both an apparatus and a method for accomplishing the purposes of the invention. 5 figs.

  6. System and method for delivery of neutron beams for medical therapy

    DOEpatents

    Nigg, David W.; Wemple, Charles A.

    1999-01-01

    A neutron delivery system that provides improved capability for tumor control during medical therapy. The system creates a unique neutron beam that has a bimodal or multi-modal energy spectrum. This unique neutron beam can be used for fast-neutron therapy, boron neutron capture therapy (BNCT), or both. The invention includes both an apparatus and a method for accomplishing the purposes of the invention.

  7. 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.

  8. 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.

  9. Neutron Capture Cross Sections of 236U and 234U

    SciTech Connect

    Rundberg, R. S.; Bredeweg, T. A.; Bond, E. M.; Haight, R. C.; Hunt, L. F.; O'Donnell, J. M.; Schwantes, J. M.; Ullmann, J. L.; Vieira, D. J.; Wilhelmy, J. B.; Wouters, J. M.; Kronenberg, A.

    2006-03-13

    Accurate neutron capture cross sections of the actinide elements at neutron energies up to 1 MeV are needed to better interpret archived nuclear test data, for post-detonation nuclear attribution, and the Advanced Fuel Cycle Initiative. The Detector for Advance Neutron Capture Experiments, DANCE, has unique capabilities that allow the differentiation of capture gamma rays from fission gamma rays and background gamma rays from scattered neutrons captured by barium isotopes in the barium fluoride scintillators. The DANCE array has a high granularity, 160 scintillators, high efficiency, and nearly 4-{pi} solid angle. Through the use of cuts in cluster multiplicity and calorimetric energy the capture gamma-rays are differentiated from other sources of gamma rays. The preliminary results for the capture cross sections of 236U are in agreement with the ENDF/B-VI evaluation. The preliminary results for 234U lower are than ENDF/B-VI evaluation and are closer to older evaluations.

  10. Boron neutron capture irradiation: setting up a clinical programme in Nice.

    PubMed

    Pignol, J P; Chauvel, P; Paquis, P; Courdi, A; Iborra-Brassart, N; Lonjon, M; Lebrun-Frenay, C; Frenay, M; Grellier, P; Chatel, M; Hérault, J; Bensadoun, R J; Milano, G; Nepveu, F; Patau, J P; Demard, F; Breteau, N

    1996-01-01

    Neutron capture irradiation aims to selectively destroy tumor cells using 10B(n,alpha)7Li nuclear reactions produced within themselves. Following the capture reaction, an alpha particle and a, 7Li ion are emitted. Carrying an energy of 2.79 MeV, they destroy all molecular structures along their path close to 10 microns. These captures, used exclusively with a 'slow' neutron irradiation, provide a neutron capture therapy (BNCT). If they are used in addition to a fast neutron beam irradiation, they provide a neutron capture potentiation (NCP). The Centre Antoine-Lacassagne in Nice is actively involved in the European Demonstration Project for BNCT of grade IV glioblastomas (GBM) after surgical excision and BSH administration. Taking into account the preliminary results obtained in Japan, work on an 'epithermal' neutron target compatible with various cyclotron beams is in progress to facilitate further developments of this technique. For NCP, thermalized neutron yield has been measured in phantoms irradiated in the fast neutron beam of the biomedical cyclotron in Nice. A thermal peak appears after 5 cm depth in the tissues, delayed after the fast neutron peak at 1.8 cm depth. Thus, a physical overdosage of 10% may be obtained if 100 ppm of 10B are assumed in the tissues. Our results using CAL 58 GBM cell line demonstrate a dose modification factor (DMF) of 1.19 when 100 ppm of boric acid are added to the growth medium. Thus for the particles, issued from neutron capture, a biological efficiency at least twice that of fast neutrons can be derived. These results, compared with historical data on fast neutron irradiation of glioblastoma, suggest that a therapeutic window may be obtained for GBM.

  11. PGNAA of human arthritic synovium for boron neutron capture synovectomy

    SciTech Connect

    Binello, E.; Yanch, J.C.; Shortkroff, S.

    1997-12-01

    Boron neutron capture synovectomy (BNCS), is a proposed new therapy modality for the treatment of rheumatoid arthritis, an autoimmune disease afflicting the joints. The synovium, which is the membrane lining the joint, becomes inflamed and represents the target tissue for therapy. When a joint is unresponsive to drug treatment, physical removal of the synovium, termed synovectomy, becomes necessary. Existing options include surgery and radiation synovectomy. BNCS has advantages over these options in that it is noninvasive and does not require the administration of radioactive substances. Previous studies have shown that the uptake of {sup 10}B by human arthritic synovium ex vivo is high, ranging from 194 to 545 ppm with an unenriched boron compound. While tissue samples remain viable up to 1 week, ex vivo conditions do not accurately reflect those in vivo. This paper presents results from experiments assessing the washout of boron from the tissue and examines the implications for in vivo studies.

  12. Computational assessment of deep-seated tumor treatment capability of the 9Be(d,n)10B reaction for accelerator-based boron neutron capture therapy (AB-BNCT).

    PubMed

    Capoulat, M E; Minsky, D M; Kreiner, A J

    2014-03-01

    The 9Be(d,n)10B reaction was studied as an epithermal neutron source for brain tumor treatment through Boron Neutron Capture Therapy (BNCT). In BNCT, neutrons are classified according to their energies as thermal (<0.5 eV), epithermal (from 0.5 eV to 10 keV) or fast (>10 keV). For deep-seated tumors epithermal neutrons are needed. Since a fraction of the neutrons produced by this reaction are quite fast (up to 5-6 MeV, even for low-bombarding energies), an efficient beam shaping design is required. This task was carried out (1) by selecting the combinations of bombarding energy and target thickness that minimize the highest-energy neutron production; and (2) by the appropriate choice of the Beam Shaping Assembly (BSA) geometry, for each of the combinations found in (1). The BSA geometry was determined as the configuration that maximized the dose deliverable to the tumor in a 1 h treatment, within the constraints imposed by the healthy tissue dose adopted tolerance. Doses were calculated through the MCNP code. The highest dose deliverable to the tumor was found for an 8 μm target and a deuteron beam of 1.45 MeV. Tumor weighted doses ≥40 Gy can be delivered up to about 5 cm in depth, with a maximum value of 51 Gy at a depth of about 2 cm. This dose performance can be improved by relaxing the treatment time constraint and splitting the treatment into two 1-h sessions. These good treatment capabilities strengthen the prospects for a potential use of this reaction in BNCT.

  13. Neutron Capture Experiments on Unstable Nuclei

    SciTech Connect

    Jon M. Schwantes; Ralf Sudowe; Heino Nitsche; Darleane C. Hoffman

    2003-12-16

    A primary objective of this project is to study neutron capture cross sections for various stable and unstable isotopes that will contribute to the Science Based Stockpile Stewardship (SBSS) program by providing improved data for modeling and interpretation of nuclear device performance. The information obtained will also be important in astrophysical modeling of nucleosynthesis. During this reporting period, the emphasis has been on preparing a radioactive target of {sup 155}Eu (half-life = 4.7 years), and several stable targets, including isotopically separated {sup 154}Sm, {sup 151}Eu, and {sup 153}Eu. Measurements of their neutron capture cross sections will be conducted in collaboration with researchers at the Los Alamos Neutron Science Center (LANSCE) facility using the Detector for Advanced Neutron Capture Experiments (DANCE). A suitable backing material (beryllium) for the targets has been selected after careful calculations of its contribution to the background of the measurements. In addition, a high voltage plating procedure has been developed and optimized. Stable targets of {sup 151}Eu and {sup 153}Eu and a target of natural Eu ({approx}50% {sup 151}Eu and {approx}50% {sup 153}Eu) have each been plated to a mass thickness of >1 mg/cm{sup 2} and delivered to the DANCE collaboration at Los Alamos National Laboratory (LANL). Natural Eu targets will be tested first to confirm that the target dimensions and backing are appropriate prior to performing measurements on the extremely valuable targets of separated isotopes. In order to prepare a target of the radioactive {sup 155}Eu, it must first be separated from the {sup 154}Sm target material that was irradiated in a very high neutron flux of 1.5x1015 neutrons/cm{sup 2}/s for 50 days. The reaction is {sup 154}Sm (n,f){sup 155}Sm (half-life = 22 minutes) {sup 155}Eu. Considerable progress has been made in developing a suitable high-yield and high-purity separation method for separating Eu from targets

  14. Large animal normal tissue tolerance with boron neutron capture

    SciTech Connect

    Gavin, P.R.; Swartz, C.D. ); Kraft, S.L. ); Briebenow, M.L. ); DeHaan, C.E.

    1994-03-30

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA[sub 2]B[sub 12]H[sub 11]SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 [times] 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood. 23 refs., 6 figs., 2 tabs.

  15. Neutron Capture Reactions on lu Isotopes at Dance

    NASA Astrophysics Data System (ADS)

    Roig, O.; Meot, V.; Daugas, J.-M.; Morel, P.; Jandel, M.; Vieira, D. J.; Bond, E. M.; Bredeweg, T. A.; Couture, A. J.; Haight, R. C.; Keksis, A. L.; Rundberg, R. S.; Ullmann, J. L.; Wouters, J. M.

    2013-03-01

    The DANCE1 (Detector for Advanced Neutron Capture Experiments) array at LANSCE spallation neutron source in Los Alamos has been used to obtain the neutron radiative capture cross sections for 175Lu and 176Lu with neutron energies from thermal up to 100 keV. Both isotopes are of current interest for the nucleosynthesis s-process.2,3 Three targets were used to perform these measurements. One was natural Lu foil of 31 mg/cm2 and the other two were isotope-enriched targets of 175Lu and 176Lu. Firstly, the cross sections were obtained by normalizing yield to a well-known cross section at the thermal neutron energy. Now, we want to obtain absolute cross sections of radiative capture through a precise neutron flux determination, an accurate target mass measurement and an efficiency determination of the DANCE array.

  16. Radiative neutron capture cross sections on 176Lu at DANCE

    NASA Astrophysics Data System (ADS)

    Roig, O.; Jandel, M.; Méot, V.; Bond, E. M.; Bredeweg, T. A.; Couture, A. J.; Haight, R. C.; Keksis, A. L.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.

    2016-03-01

    The cross section of the neutron capture reaction 176Lu(n ,γ ) has been measured for a wide incident neutron energy range with the Detector for Advanced Neutron Capture Experiments at the Los Alamos Neutron Science Center. The thermal neutron capture cross section was determined to be (1912 ±132 ) b for one of the Lu natural isotopes, 176Lu. The resonance part was measured and compared to the Mughabghab's atlas using the R -matrix code, sammy. At higher neutron energies the measured cross sections are compared to ENDF/B-VII.1, JEFF-3.2, and BRC evaluated nuclear data. The Maxwellian averaged cross sections in a stellar plasma for thermal energies between 5 keV and 100 keV were extracted using these data.

  17. Experimental Neutron Capture Rate Constraint Far from Stability.

    PubMed

    Liddick, S N; Spyrou, A; Crider, B P; Naqvi, F; Larsen, A C; Guttormsen, M; Mumpower, M; Surman, R; Perdikakis, G; Bleuel, D L; Couture, A; Crespo Campo, L; Dombos, A C; Lewis, R; Mosby, S; Nikas, S; Prokop, C J; Renstrom, T; Rubio, B; Siem, S; Quinn, S J

    2016-06-17

    Nuclear reactions where an exotic nucleus captures a neutron are critical for a wide variety of applications, from energy production and national security, to astrophysical processes, and nucleosynthesis. Neutron capture rates are well constrained near stable isotopes where experimental data are available; however, moving far from the valley of stability, uncertainties grow by orders of magnitude. This is due to the complete lack of experimental constraints, as the direct measurement of a neutron-capture reaction on a short-lived nucleus is extremely challenging. Here, we report on the first experimental extraction of a neutron capture reaction rate on ^{69}Ni, a nucleus that is five neutrons away from the last stable isotope of Ni. The implications of this measurement on nucleosynthesis around mass 70 are discussed, and the impact of similar future measurements on the understanding of the origin of the heavy elements in the cosmos is presented.

  18. Neutron Capture Gamma-Ray Libraries for Nuclear Applications

    SciTech Connect

    Sleaford, B W; Firestone, R B; Summers, N; Escher, J; Hurst, A; Krticka, M; Basunia, S; Molnar, G; Belgya, T; Revay, Z; Choi, H D

    2010-11-04

    The neutron capture reaction is useful in identifying and analyzing the gamma-ray spectrum from an unknown assembly as it gives unambiguous information on its composition. this can be done passively or actively where an external neutron source is used to probe an unknown assembly. There are known capture gamma-ray data gaps in the ENDF libraries used by transport codes for various nuclear applications. The Evaluated Gamma-ray Activation file (EGAF) is a new thermal neutron capture database of discrete line spectra and cross sections for over 260 isotopes that was developed as part of an IAEA Coordinated Research project. EGAF is being used to improve the capture gamma production in ENDF libraries. For medium to heavy nuclei the quasi continuum contribution to the gamma cascades is not experimentally resolved. The continuum contains up to 90% of all the decay energy and is modeled here with the statistical nuclear structure code DICEBOX. This code also provides a consistency check of the level scheme nuclear structure evaluation. The calculated continuum is of sufficient accuracy to include in the ENDF libraries. This analysis also determines new total thermal capture cross sections and provides an improved RIPL database. For higher energy neutron capture there is less experimental data available making benchmarking of the modeling codes more difficult. They are investigating the capture spectra from higher energy neutrons experimentally using surrogate reactions and modeling this with Hauser-Feshbach codes. This can then be used to benchmark CASINO, a version of DICEBOX modified for neutron capture at higher energy. This can be used to simulate spectra from neutron capture at incident neutron energies up to 20 MeV to improve the gamma-ray spectrum in neutron data libraries used for transport modeling of unknown assemblies.

  19. 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.

  20. Enhancing the Detector for Advanced Neutron Capture Experiments

    NASA Astrophysics Data System (ADS)

    Couture, A.; Mosby, S.; Baramsai, B.; Bredeweg, T. A.; Jandel, M.; Macon, K.; O'Donnell, J. M.; Rusev, G.; Taddeucci, T. N.; Ullmann, J. L.; Walker, C. L.

    2015-05-01

    The Detector for Advanced Neutron Capture Experiments (DANCE) has been used for extensive studies of neutron capture, gamma decay, photon strength functions, and prompt and delayed fission-gamma emission. Despite these successes, the potential measurements have been limited by the data acquisition hardware. We report on a major upgrade of the DANCE data acquisition that simultaneously enables strait-forward coupling to auxiliary detectors, including high-resolution high-purity germanium detectors and neutron tagging array. The upgrade will enhance the time domain accessible for time-of-flight neutron measurements as well as improve the resolution in the DANCE barium fluoride crystals for photons.

  1. Enhancing the detector for advanced neutron capture experiments

    SciTech Connect

    Couture, A.; Mosby, S.; Baramsai, B.; Bredeweg, T. A.; Jandel, M.; Macon, K.; O’Donnell, J. M.; Rusev, G.; Taddeucci, T. N; Ullmann, J. L.; Walker, C. L.

    2015-05-28

    The Detector for Advanced Neutron Capture Experiments (DANCE) has been used for extensive studies of neutron capture, gamma decay, photon strength functions, and prompt and delayed fission-gamma emission. Despite these successes, the potential measurements have been limited by the data acquisition hardware. We report on a major upgrade of the DANCE data acquisition that simultaneously enables strait-forward coupling to auxiliary detectors, including high-resolution high-purity germanium detectors and neutron tagging array. The upgrade will enhance the time domain accessible for time-of-flight neutron measurements as well as improve the resolution in the DANCE barium fluoride crystals for photons.

  2. Neutron detection by measuring capture gammas in a calorimetric approach

    NASA Astrophysics Data System (ADS)

    Pausch, Guntram; Herbach, Claus-Michael; Kong, Yong; Lentering, Ralf; Plettner, Cristina; Roemer, Katja; Scherwinski, Falko; Stein, Juergen; Schotanus, Paul; Wilpert, Thomas

    2011-10-01

    The neutron capture detector (NCD) is introduced as a novel detection scheme for thermal and epithermal neutrons that could provide large-area neutron counters by using common detector materials and proven technologies. The NCD is based on the fact that neutron captures are usually followed by prompt gamma cascades, where the sum energy of the gammas equals to the total excitation energy of typically 6-9 MeV. This large sum energy is measured in a calorimetric approach and taken as the signature of a neutron capture event. An NCD consists of a neutron converter, comprising of constituents with large elemental neutron capture cross-section like cadmium or gadolinium, which is embedded in common scintillator material. The scintillator must be large and dense enough to absorb with reasonable probability a portion of the sum energy that exceeds the energy of gammas emitted by common (natural, medical, industrial) radiation sources. An energy window, advantageously complemented with a multiplicity filter, then discriminates neutron capture signals against background. The paper presents experimental results obtained at the cold-neutron beam of the BER II research reactor, Helmholtz-Zentrum Berlin, and at other neutron sources with a prototype NCD, consisting of four BGO crystals with embedded cadmium sheets, and with a benchmark configuration consisting of two separate NaI(Tl) detectors. The detector responses are in excellent agreement with predictions of a simulation model developed for optimizing NCD configurations. NCDs could be deployed as neutron detectors in radiation portal monitors (RPMs). Advanced modular scintillation detector systems could even combine neutron and gamma sensitivity with excellent background suppression at minimum overall expense.

  3. Cross section expansion for direct neutron radiative capture

    SciTech Connect

    Baye, D.

    2004-07-01

    Cross sections for neutron radiative capture multiplied by the relative velocity can be expressed as a Taylor expansion in powers of the relative energy. The coefficients of this expansion are expressed in the potential model as integrals involving solutions of the radial Schroedinger equation and of its inhomogeneous energy derivatives calculated at zero energy. Similarities and differences with charged-particle capture are emphasized. The {sup 12}C(n,{gamma}){sup 13}C capture reaction is treated as an example. The coefficients of the Taylor expansion lead to simple parametrizations of the experimental partial cross sections for neutron capture to each {sup 13}C bound state.

  4. Neutron Capture Reactions for Stockpile Stewardship and Basic Science

    SciTech Connect

    Parker, W; Agvaanluvsan, U; Becker, J; Wilk, P; Wu, C; Bredeweg, T; Couture, A; Haight, R; Jandel, M; O'Donnell, J; Reifarth, R; Rundberg, R; Ullmann, J; Vieira, D; Wouters, J; Sheets, S; Mitchell, G; Becvar, F; Krticka, M

    2007-08-04

    The capture process is a nuclear reaction in which a target atom captures an incident projectile, e.g. a neutron. The excited-state compound nucleus de-excites by emitting photons. This process creates an atom that has one more neutron than the target atom, so it is a different isotope of the same element. With low energy (slow) neutron projectiles, capture is the dominant reaction, other than elastic scattering. However, with very heavy nuclei, fission competes with capture as a method of de-excitation of the compound nucleus. With higher energy (faster) incident neutrons, additional reactions are also possible, such as emission of protons or emission of multiple neutrons. The probability of a particular reaction occurring (such as capture) is referred to as the cross section for that reaction. Cross sections are very dependent on the incoming neutron's energy. Capture reactions can be studied either using monoenergetic neutron sources or 'white' neutron sources. A 'white' neutron source has a wide range of neutron energies in one neutron beam. The advantage to the white neutron source is that it allows the study of cross sections as they depend on neutron energies. The Los Alamos Neutron Science Center, located at Los Alamos National Laboratory, provides an intense white neutron source. Neutrons there are created by a high-energy proton beam from a linear accelerator striking a heavy metal (tungsten) target. The neutrons range in energy from subthermal up to very fast - over 100 MeV in energy. Low-energy neutron reaction cross sections fluctuate dramatically from one target to another, and they are very difficult to predict by theoretical modeling. The cross sections for particular capture reactions are important for defense sciences, advanced reactor concepts, transmutation of radioactive wastes and nuclear astrophysics. We now have a strong collaboration between Lawrence Livermore National Laboratory, Los Alamos National Laboratory, North Carolina State

  5. 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.

  6. FAST NEUTRON SPECTROMETER USING SPACED SEMICONDUCTORS FOR MEASURING TOTAL ENERGY OF NEUTRONS CAPTURED

    DOEpatents

    Love, T.A.; Murray, R.B.

    1964-04-14

    A fast neutron spectrometer was designed, which utilizes a pair of opposed detectors having a layer of /sup 6/LiF between to produce alpha and T pair for each neutron captured to provide signals, which, when combined, constitute a measure of neutron energy. (AEC)

  7. 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.

  8. Cosmogenic neutron-capture-produced nuclides in stony meteorites

    NASA Technical Reports Server (NTRS)

    Spergel, M. S.; Reedy, R. C.; Lazareth, O. W.; Levy, P. W.; Slatest, L. A.

    1986-01-01

    The complete neutron-flux results and production rates for Cl-36, Ni-59, and Co-60 in stony meteorites of various radii and composition are presented. The relative neutron source strengths and neutron production-versus-depth profiles were determined by using calculated H-3 production rates. The absolute source strengths were normalized to that determined for the moon by Woolum et al. (1975). The energy spectrum of the source neutrons and the neutron transport calculations, which employed the ANISN computer code, were similar to those used for the moon by Lingenfelter et al. (1972). The production rates of the three radionuclides were determined as a function of depth in various spherical meteoroids from the calculated equilibrium neutron-flux distributions and from energy-dependent neutron-capture cross sections. Rates for producing these radionuclides by spallation reactions were also calculated.

  9. In Vivo Boron Uptake Determination for Boron Neutron Capture Synovectomy

    SciTech Connect

    Binello, Emanuela; Shortkroff, Sonya; Yanch, Jacquelyn C.

    1999-06-06

    Boron neutron capture synovectomy (BNCS) has been proposed as a new application of the boron neutron capture reaction for the treatment of rheumatoid arthritis. In BNCS, a boron compound is injected into the joint space, where it is taken up by the synovium. The joint is then irradiated with neutrons of a desired energy range, inducing the boron neutron capture reaction in boron-loaded cells. Boron uptake by the synovium is an important parameter in the assessment of the potential of BNCS and in the determination of whether to proceed to animal irradiations for the testing of therapeutic efficacy. We present results from an investigation of boron uptake in vivo by the synovium.

  10. Measurement of internal conversion electrons from Gd neutron capture

    NASA Astrophysics Data System (ADS)

    Kandlakunta, P.; Cao, L. R.; Mulligan, P.

    2013-03-01

    Gadolinium (Gd) is a suitable material for neutron conversion because of its superior neutron absorption cross-section. However, the principal secondary particles that generate electron-hole pairs in a semiconductor detector after Gd neutron capture are low-energy internal conversion (IC) electrons. We measured the IC electron spectrum due to Gd neutron capture by using a thermal neutron beam and a digitizer-based multidetector spectroscopy. We also discussed the effective use of the IC electrons in the context of a twin-detector design and the associated gamma-ray rejection issues. Extensive simulations of the spectra of IC electrons and gamma rays agreed well with the experimental results; both types of results support the feasibility of the proposed n-γ separation method.

  11. Virtual Gamma Ray Radiation Sources through Neutron Radiative Capture

    SciTech Connect

    Scott Wilde, Raymond Keegan

    2008-07-01

    The countrate response of a gamma spectrometry system from a neutron radiation source behind a plane of moderating material doped with a nuclide of a large radiative neutron capture cross-section exhibits a countrate response analogous to a gamma radiation source at the same position from the detector. Using a planar, surface area of the neutron moderating material exposed to the neutron radiation produces a larger area under the prompt gamma ray peak in the detector than a smaller area of dimensions relative to the active volume of the gamma detection system.

  12. An improved method for estimating the neutron background in measurements of neutron capture reactions

    NASA Astrophysics Data System (ADS)

    Žugec, P.; Bosnar, D.; Colonna, N.; Gunsing, F.

    2016-08-01

    The relation between the neutron background in neutron capture measurements and the neutron sensitivity related to the experimental setup is examined. It is pointed out that a proper estimate of the neutron background may only be obtained by means of dedicated simulations taking into account the full framework of the neutron-induced reactions and their complete temporal evolution. No other presently available method seems to provide reliable results, in particular under the capture resonances. An improved neutron background estimation technique is proposed, the main improvement regarding the treatment of the neutron sensitivity, taking into account the temporal evolution of the neutron-induced reactions. The technique is complemented by an advanced data analysis procedure based on relativistic kinematics of neutron scattering. The analysis procedure allows for the calculation of the neutron background in capture measurements, without requiring the time-consuming simulations to be adapted to each particular sample. A suggestion is made on how to improve the neutron background estimates if neutron background simulations are not available.

  13. Neutron capture and neutron-induced fission experiments on americium isotopes with DANCE

    SciTech Connect

    Jandel, Marian

    2008-01-01

    Neutron capture cross section data on Am isotopes were measured using the Detector for Advanced Neutron Capture Experiments (DANCE) at Los Alamos National Laboratory. The neutron capture cross section was determined for {sup 241}Am for neutron energies between thermal and 320 keV. Preliminary results were also obtained for {sup 243}Am for neutron energies between 35 eV and 200 keV. The results on concurrent neutron-induced fission and neutron-capture measurements on {sup 242m}Am will be presented, where the fission events were actively triggered during the experiments. In these experiments, the Parallel-Plate Avalanche Counter (PPAC) detector that surrounds the target located in the center of the DANCE array was used as a fission-tagging detector to separate (n,{gamma}) from (n,f) events. The first evidence of neutron capture on {sup 242m}Am in the resonance region in between 2 and 9 eV of the neutron energy was obtained.

  14. Neutron capture and neutron-induced fission experiments on americium isotopes with DANCE

    SciTech Connect

    Jandel, M.; Bredeweg, T. A.; Fowler, M. M.; Bond, E. M.; Couture, A.; Haight, R. C.; Keksis, A. L.; O'Donnell, J. M.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wilhelmy, J. B.; Wouters, J. M.; Stoyer, M. A.; Wu, C. Y.; Becker, J. A.; Haslett, R. J.; Henderson, R. A.

    2009-01-28

    Neutron capture cross section data on Am isotopes were measured using the Detector for Advanced Neutron Capture Experiments (DANCE) at Los Alamos National Laboratory. The neutron capture cross section was determined for {sup 241}Am for neutron energies between thermal and 320 keV. Preliminary results were also obtained for {sup 243}Am for neutron energies between 10 eV and 250 keV. The results on concurrent neutron-induced fission and neutron-capture measurements on {sup 242m}Am will be presented where the fission events were actively triggered during the experiments. In these experiments, a Parallel-Plate Avalanche Counter (PPAC) detector that surrounds the target located in the center of the DANCE array was used as a fission-tagging detector to separate (n,{gamma}) events from (n,f) events. The first direct observation of neutron capture on {sup 242m}Am in the resonance region in between 2 and 9 eV of the neutron energy was obtained.

  15. Thermal-neutron capture for A=36-44

    SciTech Connect

    Chunmei, Z.; Firestone, R.B.

    2003-01-01

    The prompt gamma-ray data of thermal- neutron captures fornuclear mass number A=26-35 had been evaluated and published in "ATOMICDATA AND NUCLEAR DATA TABLES, 26, 511 (1981)". Since that time the manyexperimental data of the thermal-neutron captures have been measured andpublished. The update of the evaluated prompt gamma-ray data is verynecessary for use in PGAA of high-resolution analytical prompt gamma-rayspectroscopy. Besides, the evaluation is also very needed in theEvaluated Nuclear Structure Data File, ENSDF, because there are no promptgamma-ray data in ENSDF. The levels, prompt gamma-rays and decay schemesof thermal-neutron captures fornuclides (26Mg, 27Al, 28Si, 29Si, 30Si,31P, 32S, 33S, 34S, and 35Cl) with nuclear mass number A=26-35 have beenevaluated on the basis of all experimental data. The normalizationfactors, from which absolute prompt gamma-ray intensity can be obtained,and necessary comments are given in the text. The ENSDF format has beenadopted in this evaluation. The physical check (intensity balance andenergy balance) of evaluated thermal-neutron capture data has been done.The evaluated data have been put into Evaluated Nuclear Structure DataFile, ENSDF. This evaluation may be considered as an update of the promptgamma-ray from thermal-neutron capture data tables as published in"ATOMIC DATA AND NUCLEAR DATA TABLES, 26, 511 (1981)".

  16. 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

  17. Progress on the Europium Neutron-Capture Study using DANCE

    SciTech Connect

    Agvaanluvsan, U; Becker, J A; Macri, R A; Parker, W; Wilk, P; Wu, C Y; Bredeweg, T A; Esch, E; Haight, R C; O'Donnell, J M; Reifarth, R; Rundberg, R S; Schwantes, J M; Ullmann, J L; Vieira, D J; Wilhelmy, J B; Wouters, J M; Mitchell, G E; Sheets, S A; Becvar, F; Krticka, M

    2006-09-05

    The accurate measurement of neutron-capture cross sections of the Eu isotopes is important for many reasons including nuclear astrophysics and nuclear diagnostics. Neutron capture excitation functions of {sup 151,153}Eu targets were measured recently using a 4{pi} {gamma}-ray calorimeter array DANCE located at the Los Alamos Neutron Science Center for E{sub n} = 0.1-100 keV. The progress on the data analysis efforts is given in the present paper. The {gamma}-ray multiplicity distributions for the Eu targets and Be backing are significantly different. The {gamma}-ray multiplicity distribution is found to be the same for different neutron energies for both {sup 151}Eu and {sup 153}Eu. The statistical simulation to model the {gamma}-ray decay cascade is summarized.

  18. Neutron capture cross section of {sup 241}Am

    SciTech Connect

    Jandel, M.; Bredeweg, T. A.; Bond, E. M.; Chadwick, M. B.; Clement, R. R.; Couture, A.; O'Donnell, J. M.; Haight, R. C.; Kawano, T.; Reifarth, R.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wilhelmy, J. B.; Wouters, J. M.; Agvaanluvsan, U.; Parker, W. E.; Wu, C. Y.; Becker, J. A.

    2008-09-15

    The neutron capture cross section of {sup 241}Am for incident neutrons from 0.02 eV to 320 keV has been measured with the detector for advanced neutron capture experiments (DANCE) at the Los Alamos Neutron Science Center. The thermal neutron capture cross section was determined to be 665{+-}33 b. Our result is in good agreement with other recent measurements. Resonance parameters for E{sub n}<12 eV were obtained using an R-matrix fit to the measured cross section. The results are compared with values from the ENDF/B-VII.0, Mughabghab, JENDL-3.3, and JEFF-3.1 evaluations. {gamma}{sub n} neutron widths for the first three resonances are systematically larger by 5-15% than the ENDF/B-VII.0 values. The resonance integral above 0.5 eV was determined to be 1553{+-}7 b. Cross sections in the resolved and unresolved energy regions above 12 eV were calculated using the Hauser-Feshbach theory incorporating the width-fluctuation correction of Moldauer. The calculated results agree well with the measured data, and the extracted averaged resonance parameters in the unresolved resonance region are consistent with those for the resolved resonances.

  19. Thermal Neutron Capture Cross Section of {sup 22}Ne

    SciTech Connect

    Belgya, T.; Uberseder, E.; Petrich, D.; Kaeppeler, F.

    2009-01-28

    The radiative thermal neutron capture cross section of the astrophysically important {sup 22}Ne nucleus has been measured at the guided cold neutron beam of the Budapest Research Reactor. High-pressure gas-bottles filled with mixtures of enriched {sup 22}Ne and CH{sub 4} were used. The cross section was determined by means of the comparator method, and an improved decay-scheme obtained in this work. The new value for the thermal neutron cross section is 52.7{+-}0.7 mb, 18% larger than the accepted value. The influence of the new cross section on the astrophysical reaction rate is under investigation.

  20. Neutron capture cross section standards for BNL 325, Fourth Edition

    SciTech Connect

    Holden, N.E.

    1981-01-01

    This report evaluates the experimental data and recommends values for the thermal neutron cross sections and resonance integrals for the neutron capture reactions: /sup 55/Mn(n,..gamma..), /sup 59/Co(n,..gamma..) and /sup 197/Au(n,..gamma..). The failure of lithium and boron as standards due to the natural variation of the absorption cross sections of these elements is discussed. The Westcott convention, which describes the neutron spectrum as a thermal Maxwellian distribution with an epithermal component, is also discussed.

  1. A capture-gated fast neutron detection method

    NASA Astrophysics Data System (ADS)

    Liu, Yi; Yang, Yi-Gang; Tai, Yang; Zhang, Zhi

    2016-07-01

    To address the problem of the shortage of neutron detectors used in radiation portal monitors (RPMs), caused by the 3He supply crisis, research on a cadmium-based capture-gated fast neutron detector is presented in this paper. The detector is composed of many 1 cm × 1 cm × 20 cm plastic scintillator cuboids covered by 0.1 mm thick film of cadmium. The detector uses cadmium to absorb thermal neutrons and produce capture γ-rays to indicate the detection of neutrons, and uses plastic scintillator to moderate neutrons and register γ-rays. This design removes the volume competing relationship in traditional 3He counter-based fast neutron detectors, which hinders enhancement of the neutron detection efficiency. Detection efficiency of 21.66% ± 1.22% has been achieved with a 40.4 cm × 40.4 cm × 20 cm overall detector volume. This detector can measure both neutrons and γ-rays simultaneously. A small detector (20.2 cm × 20.2 cm × 20 cm) demonstrated a 3.3 % false alarm rate for a 252Cf source with a neutron yield of 1841 n/s from 50 cm away within 15 s measurement time. It also demonstrated a very low (<0.06%) false alarm rate for a 3.21×105 Bq 137Cs source. This detector offers a potential single-detector replacement for both neutron and the γ-ray detectors in RPM systems. Supported by National Natural Science Foundation of China (11175098, 11375095)

  2. Neutron Capture Reactions on Fe and Ni Isotopes for the Astrophysical s-process

    SciTech Connect

    Lederer, C.; Giubrone, G.; Massimi, C.; Žugec, P.; Barbagallo, M.; Colonna, N.; Domingo-Pardo, C.; Guerrero, C.; Gunsing, F.; Käppeler, F.; Tain, J.L.; Altstadt, S.; Andrzejewski, J.; Audouin, L.; Bečvář, F.; and others

    2014-06-15

    Neutron capture cross sections in the keV neutron energy region are the key nuclear physics input to study the astrophysical slow neutron capture process. In the past years, a series of neutron capture cross section measurements has been performed at the neutron time-of-flight facility n{sub T}OF at CERN focussing on the Fe/Ni mass region. Recent results and future developments in the neutron time-of-flight technique are discussed.

  3. Neutron transfer reactions: Surrogates for neutron capture for basic and applied nuclear science

    SciTech Connect

    Cizewski, J. A.; Jones, K. L.; Kozub, R. L.; Pain, Steven D; Peters, W. A.; Adekola, Aderemi S; Allen, J.; Bardayan, Daniel W; Becker, J.; Blackmon, Jeff C; Chae, K. Y.; Chipps, K.; Erikson, Luke; Gaddis, A. L.; Harlin, Christopher W; Hatarik, Robert; Howard, Joshua A; Jandel, M.; Johnson, Micah; Kapler, R.; Krolas, W.; Liang, J Felix; Livesay, Jake; Ma, Zhanwen; Matei, Catalin; Matthews, C.; Moazen, Brian; Nesaraja, Caroline D; O'Malley, Patrick; Patterson, N. P.; Paulauskas, Stanley; Pelham, T.; Pittman, S. T.; Radford, David C; Rogers, J.; Schmitt, Kyle; Shapira, Dan; ShrinerJr., J. F.; Sissom, D. J.; Smith, Michael Scott; Swan, T. P.; Thomas, J. S.; Vieira, D. J.; Wilhelmy, J. B.; Wilson, Gemma L

    2009-04-01

    Neutron capture reactions on unstable nuclei are important for both basic and applied nuclear science. A program has been developed at the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory to study single-neutron transfer (d,p) reactions with rare isotope beams to provide information on neutron-induced reactions on unstable nuclei. Results from (d,p) studies on {sup 130,132}Sn, {sup 134}Te and {sup 75}As are discussed.

  4. Neutron capture studies on /sup 189/Os

    SciTech Connect

    Bruce, A.M.; Colvin, G.G.; Gelletly, W.; Warner, D.D.

    1987-01-01

    An extensive study of the level structure of /sup 189/Os has been carried out using the (n,..gamma..) and (n,e-) reactions. The use of the Average Resonance Capture technique ensures that the complete set of 1/2-, 3/2- states has been established up to 1500 keV in excitation energy and secondary ..gamma..-rays have been measured in singles and coincidence to build up the detailed level scheme. 7 refs., 2 figs.

  5. Thermal Neutron Capture onto the Stable Tungsten Isotopes

    NASA Astrophysics Data System (ADS)

    Hurst, A. M.; Firestone, R. B.; Sleaford, B. W.; Summers, N. C.; Revay, Zs.; Szentmiklósi, L.; Belgya, T.; Basunia, M. S.; Capote, R.; Choi, H.; Dashdorj, D.; Escher, J.; Krticka, M.; Nichols, A.

    2012-02-01

    Thermal neutron-capture measurements of the stable tungsten isotopes have been carried out using the guided thermal-neutron beam at the Budapest Reactor. Prompt singles spectra were collected and analyzed using the HYPERMET γ-ray analysis software package for the compound tungsten systems 183W, 184W, and 187W, prepared from isotopically-enriched samples of 182W, 183W, and 186W, respectively. These new data provide both confirmation and new insights into the decay schemes and structure of the tungsten isotopes reported in the Evaluated Gamma-ray Activation File based upon previous elemental analysis. The experimental data have also been compared to Monte Carlo simulations of γ-ray emission following the thermal neutron-capture process using the statistical-decay code DICEBOX. Together, the experimental cross sections and modeledfeeding contribution from the quasi continuum, have been used to determine the total radiative thermal neutron-capture cross sections for the tungsten isotopes and provide improved decay-scheme information for the structural- and neutron-data libraries.

  6. Development and construction of a neutron beam line for accelerator-based boron neutron capture synovectomy.

    PubMed

    Gierga, D P; Yanch, J C; Shefer, R E

    2000-01-01

    A potential application of the 10B(n, alpha)7Li nuclear reaction for the treatment of rheumatoid arthritis, termed Boron Neutron Capture Synovectomy (BNCS), is under investigation. In an arthritic joint, the synovial lining becomes inflamed and is a source of great pain and discomfort for the afflicted patient. The goal of BNCS is to ablate the synovium, thereby eliminating the symptoms of the arthritis. A BNCS treatment would consist of an intra-articular injection of boron followed by neutron irradiation of the joint. Monte Carlo radiation transport calculations have been used to develop an accelerator-based epithermal neutron beam line for BNCS treatments. The model includes a moderator/reflector assembly, neutron producing target, target cooling system, and arthritic joint phantom. Single and parallel opposed beam irradiations have been modeled for the human knee, human finger, and rabbit knee joints. Additional reflectors, placed to the side and back of the joint, have been added to the model and have been shown to improve treatment times and skin doses by about a factor of 2. Several neutron-producing charged particle reactions have been examined for BNCS, including the 9Be(p,n) reaction at proton energies of 4 and 3.7 MeV, the 9Be(d,n) reaction at deuteron energies of 1.5 and 2.6 MeV, and the 7Li(p,n) reaction at a proton energy of 2.5 MeV. For an accelerator beam current of 1 mA and synovial boron uptake of 1000 ppm, the time to deliver a therapy dose of 10,000 RBEcGy ranges from 3 to 48 min, depending on the treated joint and the neutron producing charged particle reaction. The whole-body effective dose that a human would incur during a knee treatment has been estimated to be 3.6 rem or 0.75 rem, for 1000 ppm or 19,000 ppm synovial boron uptake, respectively, although the shielding configuration has not yet been optimized. The Monte Carlo design process culminated in the construction, installation, and testing of a dedicated BNCS beam line on the high

  7. Direct Neutron Capture Calculations with Covariant Density Functional Theory Inputs

    NASA Astrophysics Data System (ADS)

    Zhang, Shi-Sheng; Peng, Jin-Peng; Smith, Michael S.; Arbanas, Goran; Kozub, Ray L.

    2014-09-01

    Predictions of direct neutron capture are of vital importance for simulations of nucleosynthesis in supernovae, merging neutron stars, and other astrophysical environments. We calculate the direct capture cross sections for E1 transitions using nuclear structure information from a covariant density functional theory as input for the FRESCO coupled-channels reaction code. We find good agreement of our predictions with experimental cross section data on the double closed-shell targets 16O, 48Ca, and 90Zr, and the exotic nucleus 36S. Extensions of the technique for unstable nuclei and for large-scale calculations will be discussed. Predictions of direct neutron capture are of vital importance for simulations of nucleosynthesis in supernovae, merging neutron stars, and other astrophysical environments. We calculate the direct capture cross sections for E1 transitions using nuclear structure information from a covariant density functional theory as input for the FRESCO coupled-channels reaction code. We find good agreement of our predictions with experimental cross section data on the double closed-shell targets 16O, 48Ca, and 90Zr, and the exotic nucleus 36S. Extensions of the technique for unstable nuclei and for large-scale calculations will be discussed. Supported by the U.S. Dept. of Energy, Office of Nuclear Physics.

  8. Neutron-capture nucleosynthesis in the first stars

    SciTech Connect

    Roederer, Ian U.; Preston, George W.; Thompson, Ian B.; Shectman, Stephen A.; Sneden, Christopher

    2014-04-01

    Recent studies suggest that metal-poor stars enhanced in carbon but containing low levels of neutron-capture elements may have been among the first to incorporate the nucleosynthesis products of the first generation of stars. We have observed 16 stars with enhanced carbon or nitrogen using the MIKE Spectrograph on the Magellan Telescopes at Las Campanas Observatory and the Tull Spectrograph on the Smith Telescope at McDonald Observatory. We present radial velocities, stellar parameters, and detailed abundance patterns for these stars. Strontium, yttrium, zirconium, barium, europium, ytterbium, and other heavy elements are detected. In four stars, these heavy elements appear to have originated in some form of r-process nucleosynthesis. In one star, a partial s-process origin is possible. The origin of the heavy elements in the rest of the sample cannot be determined unambiguously. The presence of elements heavier than the iron group offers further evidence that zero-metallicity rapidly rotating massive stars and pair instability supernovae did not contribute substantial amounts of neutron-capture elements to the regions where the stars in our sample formed. If the carbon- or nitrogen-enhanced metal-poor stars with low levels of neutron-capture elements were enriched by products of zero-metallicity supernovae only, then the presence of these heavy elements indicates that at least one form of neutron-capture reaction operated in some of the first stars.

  9. Radiative neutron capture: Hauser Feshbach vs. statistical resonances

    NASA Astrophysics Data System (ADS)

    Rochman, D.; Goriely, S.; Koning, A. J.; Ferroukhi, H.

    2017-01-01

    The radiative neutron capture rates for isotopes of astrophysical interest are commonly calculated on the basis of the statistical Hauser Feshbach (HF) reaction model, leading to smooth and monotonically varying temperature-dependent Maxwellian-averaged cross sections (MACS). The HF approximation is known to be valid if the number of resonances in the compound system is relatively high. However, such a condition is hardly fulfilled for keV neutrons captured on light or exotic neutron-rich nuclei. For this reason, a different procedure is proposed here, based on the generation of statistical resonances. This novel technique, called the "High Fidelity Resonance" (HFR) method is shown to provide similar results as the HF approach for nuclei with a high level density but to deviate and be more realistic than HF predictions for light and neutron-rich nuclei or at relatively low sub-keV energies. The MACS derived with the HFR method are systematically compared with the traditional HF calculations for some 3300 neutron-rich nuclei and shown to give rise to significantly larger predictions with respect to the HF approach at energies of astrophysical relevance. For this reason, the HF approach should not be applied to light or neutron-rich nuclei. The Doppler broadening of the generated resonances is also studied and found to have a negligible impact on the calculated MACS.

  10. Neutron capture nuclei-containing carbon nanoparticles for destruction of cancer cells.

    PubMed

    Hwang, Kuo Chu; Lai, Po Dong; Chiang, Chi-Shiun; Wang, Pei-Jen; Yuan, Chiun-Jye

    2010-11-01

    HeLa cells were incubated with neutron capture nuclei (boron-10 and gadolinium)-containing carbon nanoparticles, followed by irradiation of slow thermal neutron beam. Under a neutron flux of 6 x 10(11) n/cm(2) (or 10 min irradiation at a neutron flux of 1 x 10(9) n/cm(2) s), the percentages of acute cell death at 8 h after irradiation are 52, 55, and 28% for HeLa cells fed with BCo@CNPs, GdCo@CNPs, and Co@CNPs, respectively. The proliferation capability of the survived HeLa cells was also found to be significantly suppressed. At 48 h after neutron irradiation, the cell viability further decreases to 35 +/- 5% as compared to the control set receiving the same amount of neutron irradiation dose but in the absence of carbon nanoparticles. This work demonstrates "proof-of-concept" examples of neutron capture therapy using (10)B-, (157)Gd-, and (59)Co-containing carbon nanoparticles for effective destruction of cancer cells. It will also be reported the preparation and surface functionalization of boron or gadolinium doped core-shell cobalt/carbon nanoparticles (BCo@CNPs, GdCo@CNPs and Co@CNPs) using a modified DC pulsed arc discharge method, and their characterization by various spectroscopic measurements, including TEM, XRD, SQUID, FT-IR, etc. Tumor cell targeting ability was introduced by surface modification of these carbon nanoparticles with folate moieties.

  11. Neutron capture measurements on unstable nuclei at LANSCE

    SciTech Connect

    Ullmann, J. L.; Haight, R. C.; Fowler, M. M.; Miller, G. G.; Rundberg, R. S.; Wilhelmy, J. B.

    1999-06-10

    Although neutron capture by stable isotopes has been extensively measured, there are very few measurements on unstable isotopes. The intense neutron flux at the Manual Lujan Jr. Neutron Scattering Center at LANSCE enables us to measure capture on targets with masses of about 1 mg over the energy range from 1 eV to 100 keV. These measurements are important not only for understanding the basic physics, but also for calculations of stellar nucleosynthesis and Science-Based Stockpile Stewardship. Preliminary measurements on {sup 169}Tm and {sup 171}Tm have been made with deuterated benzene detectors. A new detector array at the Lujan center and a new radioactive isotope separator will combine to give Los Alamos a unique capability for making these measurements.

  12. Misassigned neutron resonances of 142Nd and stellar neutron capture cross sections

    NASA Astrophysics Data System (ADS)

    Katabuchi, Tatsuya; Matsuhashi, Taihei; Terada, Kazushi; Igashira, Masayuki; Mizumoto, Motoharu; Hirose, Kentaro; Kimura, Atsushi; Iwamoto, Nobuyuki; Hara, Kaoru Y.; Harada, Hideo; Hori, Jun-ichi; Kamiyama, Takashi; Kino, Koichi; Kitatani, Fumito; Kiyanagi, Yoshiaki; Nakamura, Shoji; Toh, Yosuke

    2015-03-01

    Time-of-flight spectra of the neutron capture events of 142Nd were measured using a spallation neutron source at the Japan Proton Accelerator Research Complex. The first six resonances of 142Nd reported in a previous work were not observed. The experimental results and cross-search of resonance energies in nuclear data libraries suggested that resonances of the impurity nuclide 141Pr have been mistakenly assigned as 142Nd in the previous experiment. To investigate the impact of the nonexistence of the resonances on the s -process nucleosynthesis model, the Maxwellian averaged neutron capture cross sections with and without the misassigned resonances were compared.

  13. Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

    SciTech Connect

    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.

    2014-11-11

    Unilamellar liposomes formulated with an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the lipid bilayer, and encapsulating Na3[1-(2’-B10-H9)-2-NH3B10H8] were prepared by probe sonication and investigated in vivo. Microwave assisted digestion followed by inductively coupled plasma-optical emission spectroscopy was utilized to determine the biodistribution of boron in various tissues following either a single tail vein injection or two identical injections (separated by 24 hours) of the liposomal suspension in BALB/c mice bearing EMT6 mammary adenocarcinomas in their right flank. Double-injection protocols resulted in a boron content in the tumor exceeding 50 µg of boron per gram of tissue for 48 to 72 hours subsequent to the initial injection while tumor:blood boron ratios were more ideal from 54 hours (1.9:1) to 96 hours (5.7:1) subsequent to the initial injection. Tumor bearing mice were given a double-injection of liposomes containing the 10B-enriched analogs of the aforementioned agents and subjected to a 30 minute irradiation by thermal neutrons with a flux of 8.8 x 108 (±7%) neutrons/cm2 s integrated over the energy range of 0.0 – 0.414 eV. Significant tumor response for a single BNCT treatment was demonstrated by growth curves versus a control group. Vastly diminished tumor growth was witnessed at 14 days (186% increase versus 1551% in controls) in mice that were given a second injection/radiation treatment 7 days after the first. Mice given a one hour neutron irradiation following the double-injection of liposomes had a similar response (169% increase at 14 days) suggesting that neutron fluence is the limiting factor towards BNCT efficacy in this study.

  14. Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats.

    PubMed

    Pozzi, Emiliano C C; Trivillin, Verónica A; Colombo, Lucas L; Monti Hughes, Andrea; Thorp, Silvia I; Cardoso, Jorge E; Garabalino, Marcela A; Molinari, Ana J; Heber, Elisa M; Curotto, Paula; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Schwint, Amanda E

    2013-11-01

    Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 ± 6.6 for Sham, 7.8 ± 4.1 for Beam only, 4.4 ± 5.6 for BPA-BNCT I and 0.45 ± 0.20 for BPA-BNCT II; tumor nodule weight was 750 ± 480 mg for Sham, 960 ± 620 mg for Beam only, 380 ± 720 mg for BPA-BNCT I and 7.3 ± 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.

  15. Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats

    SciTech Connect

    Emiliano C. C. Pozzi; Veronica A. Trivilin; Lucas L. Colombo; Andrea Monti Hughes; Silvia I. Thorp; Jorge E. Cardoso; Marcel A. Garabalino; Ana J. Molinari; Elisa M. Heber; Paula Curotto; Marcelo Miller; Maria E. Itoiz; Romina F. Aromando; David W. Nigg; Amanda E. Schwint

    2013-11-01

    Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 +/- 6.6 for Sham, 7.8 +/- 4.1 for Beam only, 4.4 +/- 5.6 for BPA-BNCT I and 0.45 +/- 0.20 for BPA-BNCT II; tumor nodule weight was 750 +/- 480 mg for Sham, 960 +/- 620 mg for Beam only, 380 +/- 720 mg for BPA-BNCT I and 7.3 +/- 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.

  16. 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

  17. Gadolinium neutron capture brachytherapy (GdNCB), a new treatment method for intravascular brachytherapy

    SciTech Connect

    Enger, Shirin A.; Rezaei, Arash; Munck af Rosenschoeld, Per; Lundqvist, Hans

    2006-01-15

    Restenosis is a major problem after balloon angioplasty and stent implantation. The aim of this study is to introduce gadolinium neutron capture brachytherapy (GdNCB) as a suitable modality for treatment of stenosis. The utility of GdNCB in intravascular brachytherapy (IVBT) of stent stenosis is investigated by using the GEANT4 and MCNP4B Monte Carlo radiation transport codes. To study capture rate, Kerma, absorbed dose and absorbed dose rate around a Gd-containing stent activated with neutrons, a 30 mm long, 5 mm diameter gadolinium foil is chosen. The input data is a neutron spectrum used for clinical neutron capture therapy in Studsvik, Sweden. Thermal neutron capture in gadolinium yields a spectrum of high-energy gamma photons, which due to the build-up effect gives an almost flat dose delivery pattern to the first 4 mm around the stent. The absorbed dose rate is 1.33 Gy/min, 0.25 mm from the stent surface while the dose to normal tissue is in order of 0.22 Gy/min, i.e., a factor of 6 lower. To spare normal tissue further fractionation of the dose is also possible. The capture rate is relatively high at both ends of the foil. The dose distribution from gamma and charge particle radiation at the edges and inside the stent contributes to a nonuniform dose distribution. This will lead to higher doses to the surrounding tissue and may prevent stent edge and in-stent restenosis. The position of the stent can be verified and corrected by the treatment plan prior to activation. Activation of the stent by an external neutron field can be performed days after catherization when the target cells start to proliferate and can be expected to be more radiation sensitive. Another advantage of the nonradioactive gadolinium stent is the possibility to avoid radiation hazard to personnel.

  18. Review of Livermore-Led Neutron Capture Studies Using DANCE

    SciTech Connect

    Parker, W; Sheets, S; Agvaanluvsan, U; Becker, J; Becvar, F; Bredeweg, T; Clement, R; Couture, A; Esch, E; Haight, R; Jandel, M; Krticka, M; Mitchell, G; Macri, R; O'Donnell, J; Reifarth, R; Rundberg, R; Schwantes, J; Ullmann, J; Vieira, D; Wouters, J; Wilk, P

    2007-05-11

    We have made neutron capture cross-section measurements using the white neutron source at the Los Alamos Science Center, the DANCE detector array (Detector for Advanced Neutron Capture Experiments) and targets important for basic science and stockpile stewardship. In this paper, we review results from (n,{gamma}) reactions on {sup 94,95}Mo, {sup 152,154,157,160,nat}Gd, {sup 151,153}Eu and {sup 242m}Am for neutron energies from < 1eV up to {approx} 20 keV. We measured details of the {gamma}-ray cascade following neutron capture, for comparison with results of statistical model simulations. We determined the neutron energy dependent (n,{gamma}) cross section and gained information about statistical decay properties, including the nuclear level density and the photon strength function. Because of the high granularity of the detector array, it is possible to look at gamma cascades with a specified number of transitions (a specific multiplicity). We simulated {gamma}-ray cascades using a combination of the DICEBOX/GEANT computer codes. In the case of the deformed nuclei, we found evidence of a scissors-mode resonance. For the Eu, we also determined the (n,{gamma}) cross sections. For the {sup 94,95}Mo, we focused on the spin and parity assignments of the resonances and the determination of the photon strength functions for the compound nuclei {sup 95,96}Mo. Future plans include measurements on actinide targets; our immediate interest is in {sup 242m}Am.

  19. SU-E-J-104: Single Photon Image From PET with Insertable SPECT Collimator for Boron Neutron Capture Therapy: A Feasibility Study

    SciTech Connect

    Jung, J; Yoon, D; Suh, T

    2014-06-01

    Purpose: The aim of our proposed system is to confirm the feasibility of extraction of two types of images from one positron emission tomography (PET) module with an insertable collimator for brain tumor treatment during the BNCT. Methods: Data from the PET module, neutron source, and collimator was entered in the Monte Carlo n-particle extended (MCNPX) source code. The coincidence events were first compiled on the PET detector, and then, the events of the prompt gamma ray were collected after neutron emission by using a single photon emission computed tomography (SPECT) collimator on the PET. The obtaining of full width at half maximum (FWHM) values from the energy spectrum was performed to collect effective events for reconstructed image. In order to evaluate the images easily, five boron regions in a brain phantom were used. The image profiles were extracted from the region of interest (ROI) of a phantom. The image was reconstructed using the ordered subsets expectation maximization (OSEM) reconstruction algorithm. The image profiles and the receiver operating characteristic (ROC) curve were compiled for quantitative analysis from the two kinds of reconstructed image. Results: The prompt gamma ray energy peak of 478 keV appeared in the energy spectrum with a FWHM of 41 keV (6.4%). On the basis of the ROC curve in Region A to Region E, the differences in the area under the curve (AUC) of the PET and SPECT images were found to be 10.2%, 11.7%, 8.2% (center, Region C), 12.6%, and 10.5%, respectively. Conclusion: We attempted to acquire the PET and SPECT images simultaneously using only PET without an additional isotope. Single photon images were acquired using an insertable collimator on a PET detector. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning (MSIP)(Grant No

  20. Proposed experiment to measure {gamma}-rays from the thermal neutron capture of gadolinium

    SciTech Connect

    Yano, Takatomi; Ou, I.; Izumi, T.; Yamaguchi, R.; Mori, T.; Sakuda, M.

    2012-11-12

    Gadolinium-157 ({sup 157}Gd) has the largest thermal neutron capture cross section among any stable nuclei. The thermal neutron capture yields {gamma}-ray cascade with total energy of about 8 MeV. Because of these characteristics, Gd is applied for the recent neutrino detectors. Here, we propose an experiment to measure the multiplicity and the angular correlation of {gamma}-rays from the Gd neutron capture. With these information, we expect the improved identification of the Gd neutron capture.

  1. Neutron radiative capture methods for surface elemental analysis

    USGS Publications Warehouse

    Trombka, J.I.; Senftle, F.; Schmadebeck, R.

    1970-01-01

    Both an accelerator and a 252Cf neutron source have been used to induce characteristic gamma radiation from extended soil samples. To demonstrate the method, measurements of the neutron-induced radiative capture and activation gamma rays have been made with both Ge(Li) and NaI(Tl) detectors, Because of the possible application to space flight geochemical analysis, it is believed that NaI(Tl) detectors must be used. Analytical procedures have been developed to obtain both qualitative and semiquantitative results from an interpretation of the measured NaI(Tl) pulse-height spectrum. Experiment results and the analytic procedure are presented. ?? 1970.

  2. Neutron capture cross section of {sup 102}Pd

    SciTech Connect

    Duncan, C.L.; Krane, K.S.

    2005-05-01

    The cross sections for radiative neutron capture by {sup 102}Pd have been deduced from a measurement of the {gamma} rays emitted by 17.0-d {sup 103}Pd. The thermal cross section has been determined to be {sigma}=1.82{+-}0.20 b, and the effective resonance integral is I=23{+-}4 b. We also report thermal and resonance capture cross sections for {sup 108}Pd and note possible inconsistencies with the presently accepted values of the {sup 110}Pd cross sections.

  3. Stellar neutron capture cross sections of the Lu isotopes

    SciTech Connect

    Wisshak, K.; Voss, F.; Kaeppeler, F.; Kazakov, L.

    2006-01-15

    The neutron capture cross sections of {sup 175}Lu and {sup 176}Lu have been measured in the energy range 3-225 keV at the Karlsruhe 3.7 MV Van de Graaff accelerator. Neutrons were produced via the {sup 7}Li(p,n){sup 7}Be reaction by bombarding metallic Li targets with a pulsed proton beam, and capture events were registered with the Karlsruhe 4{pi} barium fluoride detector. The cross sections were determined relative to the gold standard using isotopically enriched as well as natural lutetium oxide samples. Overall uncertainties of {approx}1% could be achieved in the final cross section ratios to the gold standard, about a factor of 5 smaller than in previous works. Maxwellian averaged neutron capture cross sections were calculated for thermal energies between kT = 8 and 100 keV. These values are systematically larger by {approx}7% than those reported in recent evaluations. These results are of crucial importance for the assessment of the s-process branchings at A 175/176.

  4. Stellar neutron capture cross sections of the tin isotopes

    SciTech Connect

    Wisshak, K.; Voss, F.; Theis, C.; Kaeppeler, F.; Guber, K.; Kazakov, L.; Kornilov, N.; Reffo, G.

    1996-09-01

    The neutron capture cross sections of {sup 114}Sn, {sup 115}Sn, {sup 116}Sn, {sup 117}Sn, {sup 118}Sn, and {sup 120}Sn were measured in the energy range from 3 to 225 keV at the Karlsruhe 3.75 MV Van de Graaff accelerator. Neutrons were produced via the {sup 7}Li({ital p},{ital n}){sup 7}Be reaction using a pulsed proton beam. Capture events were registered with the Karlsruhe 4{pi} barium fluoride detector. The experiment was complicated by the small ({ital n},{gamma}) cross sections of the proton magic tin isotopes and by the comparably low enrichment of the rare isotopes {sup 114}Sn and {sup 115}Sn. Despite significant corrections for capture of scattered neutrons and for isotopic impurities, the high efficiency and the spectroscopic quality of the BaF{sub 2} detector allowed the determination of the cross-section ratios with overall uncertainties of 1{endash}2{percent}, five times smaller compared to existing data. Based on these results, Maxwellian averaged ({ital n},{gamma}) cross sections were calculated for thermal energies between {ital kT}=10 and 100 keV. These data are used for a discussion of the solar tin abundance and for an improved determination of the isotopic {ital s}- and {ital r}-process components. {copyright} {ital 1996 The American Physical Society.}

  5. Modern alchemy: Fred Hoyle and element building by neutron capture

    NASA Astrophysics Data System (ADS)

    Burbidge, E. Margaret

    Fred Hoyle's fundamental work on building the chemical elements by nuclear processes in stars at various stages in their lives began with the building of elements around iron in the very dense hot interiors of stars. Later, in the paper by Burbidge, Burbidge, Fowler and Hoyle, we four showed that Hoyle's "equilibrium process" is one of eight processes required to make all of the isotopes of all the elements detected in the Sun and stars. Neutron capture reactions, which Fred had not considered in his epochal 1946 paper, but for which experimental data were just becoming available in 1957, are very important, in addition to the energy-generating reactions involving hydrogen, helium, carbon, nitrogen and oxygen, for building all of the elements. They are now providing clues to the late stages of stellar evolution and the earliest history of our Galaxy. I describe here our earliest observational work on neutron capture processes in evolved stars, some new work on stars showing the results of the neutron capture reactions, and data relating to processes ending in the production of lead, and I discuss where this fits into the history of stars in our own Galaxy.

  6. Microdosimetric investigations at the fast neutron therapy facility at Fermilab

    SciTech Connect

    Langen, K.M.

    1997-12-01

    Microdosimetry was used to investigate three issues at the neutron therapy facility (NTF) at Fermilab. Firstly, the conversion factor from absorbed dose in A-150 tissue equivalent plastic to absorbed dose in ICRU tissue was determined. For this, the effective neutron kerma factor ratios, i.e., oxygen tissue equivalent plastic and carbon to A-150 tissue equivalent plastic, were measured in the neutron beam. An A-150 tissue equivalent plastic to ICRU tissue absorbed dose conversion factor of 0.92 {+-} 0.04 was determined. Secondly, variations in the radiobiological effectiveness (RBE) in the beam were mapped by determining variations in two related quantities, e{sup *} and R, with field size and depth in tissue. Maximal variation in e{sup *} and R of 9% and 15% respectively were determined. Lastly, the feasibility of utilizing the boron neutron capture reaction on boron-10 to selectively enhance the tumor dose in the NTF beam was investigated.

  7. Neutron capture and (n,2n) measurements on 241Am

    SciTech Connect

    Vieira, D; Jandel, M; Bredeweg, T; Bond, E; Clement, R; Couture, A; Haight, R; O'Donnell, J; Reifarth, R; Ullmann, J; Wilhelmy, J; Wouters, J; Tonchev, A; Hutcheson, A; Angell, C; Crowell, A; Fallin, B; Hammond, S; Howell, C; Karowowski, H; Kelley, J; Pedroni, R; Tornow, W; Macri, R; Agvaanluvsan, U; Becker, J; Dashdorj, D; Stoyer, M; Wu, C

    2007-07-18

    We report on a set of neutron-induced reaction measurements on {sup 241}Am which are important for nuclear forensics and advanced nuclear reactor design. Neutron capture measurements have been performed on the DANCE detector array at the Los Alamos Neutron Scattering CEnter (LANSCE). In general, good agreement is found with the most recent data evaluations up to an incident neutron energy of {approx} 300 keV where background limits the measurement. Using mono-energetic neutrons produced in the {sup 2}H(d,n){sup 3}He reaction at Triangle University Nuclear Laboratory (TUNL), we have measured the {sup 241}Am(n,2n) excitation function from threshold (6.7 MeV) to 14.5 MeV using the activation method. Good agreement is found with previous measurements, with the exception of the three data points reported by Perdikakis et al. around 11 MeV, where we obtain a much lower cross section that is more consistent with theoretical estimates.

  8. Thermal neutron capture cross sections of the potassium isotopes

    NASA Astrophysics Data System (ADS)

    Firestone, R. B.; Krtička, M.; Révay, Zs.; Szentmiklosi, L.; Belgya, T.

    2013-02-01

    Precise thermal neutron capture γ-ray cross sections σγ for 39,40,41K were measured on a natural potassium target with the guided neutron beam at the Budapest Reactor. The cross sections were internally standardized using a stoichiometric KCl target with well-known 35Cl(n,γ) γ-ray cross sections [Révay and Molnár, Radiochimica ActaRAACAP0033-823010.1524/ract.91.6.361.20027 91, 361 (2003); Molnár, Révay, and Belgya, Nucl. Instrum. Meth. Phys. Res. BNIMBEU0168-583X10.1016/S0168-583X(03)01529-5 213, 32 (2004)]. These data were combined with γ-ray intensities from von Egidy [von Egidy, Daniel, Hungerford, Schmidt, Lieb, Krusche, Kerr, Barreau, Borner, Brissot , J. Phys. G. Nucl. Phys.JPHGBM0305-461610.1088/0305-4616/10/2/013 10, 221 (1984)] and Krusche [Krusche, Lieb, Ziegler, Daniel, von Egidy, Rascher, Barreau, Borner, and Warner, Nucl. Phys. ANUPABL0375-947410.1016/0375-9474(84)90506-2 417, 231 (1984); Krusche, Winter, Lieb, Hungerford, Schmidt, von Egidy, Scheerer, Kerr, and Borner, Nucl. Phys. ANUPABL0375-947410.1016/0375-9474(85)90429-4 439, 219 (1985)] to generate nearly complete capture γ-ray level schemes. Total radiative neutron cross sections were deduced from the total γ-ray cross section feeding the ground state, σ0=Σσγ(GS) after correction for unobserved statistical γ-ray feeding from levels near the neutron capture energy. The corrections were performed with Monte Carlo simulations of the potassium thermal neutron capture decay schemes using the computer code dicebox where the simulated populations of low-lying levels are normalized to the measured cross section depopulating those levels. Comparisons of the simulated and experimental level feeding intensities have led to proposed new spins and parities for selected levels in the potassium isotopes where direct reactions are not a significant contribution. We determined the total radiative neutron cross sections σ0(39K)=2.28±0.04 b, σ0(40K)=90±7 b, and σ0(41K)=1.62±0.03 b from the

  9. Monte Carlo calculations of thermal neutron capture in gadolinium: a comparison of GEANT4 and MCNP with measurements.

    PubMed

    Enger, Shirin A; Munck af Rosenschöld, Per; Rezaei, Arash; Lundqvist, Hans

    2006-02-01

    GEANT4 is a Monte Carlo code originally implemented for high-energy physics applications and is well known for particle transport at high energies. The capacity of GEANT4 to simulate neutron transport in the thermal energy region is not equally well known. The aim of this article is to compare MCNP, a code commonly used in low energy neutron transport calculations and GEANT4 with experimental results and select the suitable code for gadolinium neutron capture applications. To account for the thermal neutron scattering from chemically bound atoms [S(alpha,beta)] in biological materials a comparison of thermal neutron fluence in tissue-like poly(methylmethacrylate) phantom is made with MCNP4B, GEANT4 6.0 patch1, and measurements from the neutron capture therapy (NCT) facility at the Studsvik, Sweden. The fluence measurements agreed with MCNP calculated results considering S(alpha,beta). The location of the thermal neutron peak calculated with MCNP without S(alpha,beta) and GEANT4 is shifted by about 0.5 cm towards a shallower depth and is 25%-30% lower in amplitude. Dose distribution from the gadolinium neutron capture reaction is then simulated by MCNP and compared with measured data. The simulations made by MCNP agree well with experimental results. As long as thermal neutron scattering from chemically bound atoms are not included in GEANT4 it is not suitable for NCT applications.

  10. Blood-brain barrier (BBB) toxicity and permeability assessment after L-(4-¹⁰Boronophenyl)alanine, a conventional B-containing drug for boron neutron capture therapy, using an in vitro BBB model.

    PubMed

    Roda, E; Nion, S; Bernocchi, G; Coccini, T

    2014-10-02

    Since brain tumours are the primary candidates for treatment by Boron Neutron Capture Therapy, one major challenge in the selective drug delivery to CNS is the crossing of the blood-brain barrier (BBB). The present pilot study investigated (i) the transport of a conventional B-containing product (i.e., L-(4-(10)Boronophenyl)alanine, L-(10)BPA), already used in medicine but still not fully characterized regarding its CNS interactions, as well as (ii) the effects of the L-(10)BPA on the BBB integrity using an in vitro model, consisting of brain capillary endothelial cells co-cultured with glial cells, closely mimicking the in vivo conditions. The multi-step experimental strategy (i.e. Integrity test, Filter study, Transport assay) checked L-(10)BPA toxicity at 80 µg Boron equivalent/ml, and its ability to cross the BBB, additionally by characterizing the cytoskeletal and TJ's proteins by immunocytochemistry and immunoblotting. In conclusion, a lack of toxic effects of L-(10)BPA was demonstrated, nevertheless accompanied by cellular stress phenomena (e.g. vimentin expression modification), paralleled by a low permeability coefficient (0.39 ± 0.01 × 10(-3)cm min(-1)), corroborating the scarce probability that L-(10)BPA would reach therapeutically effective cerebral concentration. These findings emphasized the need for novel strategies aimed at optimizing boron delivery to brain tumours, trying to ameliorate the compound uptake or developing new targeted products suitable to safely and effectively treat head cancer. Thus, the use of in vitro BBB model for screening studies may provide a useful early safety assessment for new effective compounds.

  11. Neutron Capture Measurements on Tl-isotopes at DANCE

    NASA Astrophysics Data System (ADS)

    Couture, A.; Bredeweg, T. A.; Esch, E.-I.; Jandel, M.; Haight, R. C.; O'Donnell, J. M.; Reifarth, R.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.

    2006-10-01

    The thallium isotopes play an important role in the s-process nucleosynthesis at the s-process endpoint. Furthermore, ^204Tl is one of few branch point isotopes in the endpoint region. The understanding of branch point isotopes provides modeling constraints on the temperatures during which the process takes place. The production of s-only ^204Pb is controlled entirely by ^204Tl. Measurements of the capture cross-sections of the stable Tl isotopes have recently been made using the DANCE 4-π array at LANSCE. This provides needed resonance information in the region as well as preparing the way for measurements of as yet unmeasured capture cross-section of the unstable ^204Tl. The neutron capture data for the stable isotopes as well as the plan for future measurements will be discussed.

  12. Production of Molybdenum-99 using Neutron Capture Methods

    SciTech Connect

    Toth, James J; Greenwood, Lawrence R; Soderquist, Chuck Z; Wittman, Richard S; Pierson, Bruce D; Burns, Kimberly A; Lavender, Curt A; Painter, Chad L; Love, Edward F; Wall, Donald E

    2011-01-01

    Pacific Northwest National Laboratory (PNNL), operated by Battelle, has identified a reference process for the production of molybdenum-99 (99Mo) for use in a chromatographic generator to separate the daughter product, technetium-99m (99mTc). The reference process uses the neutron capture reaction of natural or enriched molybdenum oxide via the reaction 98Mo(n,γ)99Mo. The irradiated molybdenum is dissolved in an alkaline solution, whereby the molybdenum, dissolved as the molybdate anion, is loaded on a proprietary ion exchange material in the chromatographic generator. The approach of this investigation is to provide a systematic collection of technologies to make the neutron capture method for Mo-99 production economically viable. This approach would result in the development of a technetium Tc99m generator and a new type of target. The target is comprised of molybdenum, either natural or enriched, and is tailored to the design of currently operating U.S. research reactors. The systematic collection of technologies requires evaluation of new metallurgical methods to produce the target, evaluation of target geometries tailored to research reactors, and chemical methods to dissolve the irradiated target materials for use in a chromatographic generator. A Technical specification for testing the target and neutron capture method in a research reactor is also required. This report includes identification of research and demonstration activities needed to enable deployment of neutron capture production method, including irradiations of prototypic targets, chemical processing of irradiated targets, and loading and extraction tests of Mo99 and Tc99m on the sorbent material in a prototypic generator design. The prototypical generator design is based on the proprietary method and systems for isotope product generation. The proprietary methods and systems described in this report are clearly delineated with footnotes. Ultimately, the Tc-99m generator solution provided by

  13. Scissors Mode of 162Dy Studied from Resonance Neutron Capture

    NASA Astrophysics Data System (ADS)

    Baramsai, B.; Bečvář, F.; Bredeweg, T. A.; Haight, R. C.; Jandel, M.; Kroll, J.; Krtička, M.; Mitchell, G. E.; O'Donnell, J. M.; Rundberg, R. S.; Ullmann, J. L.; Valenta, S.; Wilhelmy, J. B.

    2015-05-01

    Multi-step cascade γ-ray spectra from the neutron capture at isolated resonances of 161Dy nucleus were measured at the LANSCE/DANCE time-of-flight facility in Los Alamos National Laboratory. The objectives of this experiment were to confirm and possibly extend the spin assignment of s-wave neutron resonances and get new information on photon strength functions with emphasis on the role of the M1 scissors mode vibration. The preliminary results show that the scissors mode plays a significant role in all transitions between accessible states of the studied nucleus. The photon strength functions describing well our data are compared to results from 3He-induced reactions, (n,γ) experiments on Gd isotopes, and (γ,γ') reactions.

  14. The heavy element yields of neutron capture nucleosynthesis

    NASA Technical Reports Server (NTRS)

    Cameron, A. G. W.

    1982-01-01

    Consideration of the contribution made to the abundances of the heavy element isotopes by the S- and R-processes of nucleosynthesis has led to the determination that the previous assumption concerning the exclusive alignment of isobars to one or the other of these processes is probably in error. If the relatively small odd and even mass number abundance fluctuations characterizing R-process abundances are always the case, as assumed by this study, S-process contributions to the abundances of R-process isobars are substantial, consistent with transient flashing episodes in the S-process neutron production processes. A smooth and monotonically-decreasing curve of the abundance of the S-process yields times the neutron capture cross-section versus mass number is therefore the primary tool for the separation of the abundances due to the two processes.

  15. Scissors Mode of 162 Dy Studied from Resonance Neutron Capture

    DOE PAGES

    Baramsai, B.; Bečvář, F.; Bredeweg, T. A.; ...

    2015-05-28

    Multi-step cascade γ-ray spectra from the neutron capture at isolated resonances of 161Dy nucleus were measured at the LANSCE/DANCE time-of-flight facility in Los Alamos National Laboratory. The objectives of this experiment were to confirm and possibly extend the spin assignment of s-wave neutron resonances and get new information on photon strength functions with emphasis on the role of the M1 scissors mode vibration. The preliminary results show that the scissors mode plays a significant role in all transitions between accessible states of the studied nucleus. The photon strength functions describing well our data are compared to results from 3He-induced reactions,more » (n,γ) experiments on Gd isotopes, and (γ,γ’) reactions.« less

  16. Radiative neutron capture as a counting technique at pulsed spallation neutron sources: a review of current progress.

    PubMed

    Schooneveld, E M; Pietropaolo, A; Andreani, C; Perelli Cippo, E; Rhodes, N J; Senesi, R; Tardocchi, M; Gorini, G

    2016-09-01

    Neutron scattering techniques are attracting an increasing interest from scientists in various research fields, ranging from physics and chemistry to biology and archaeometry. The success of these neutron scattering applications is stimulated by the development of higher performance instrumentation. The development of new techniques and concepts, including radiative capture based neutron detection, is therefore a key issue to be addressed. Radiative capture based neutron detectors utilize the emission of prompt gamma rays after neutron absorption in a suitable isotope and the detection of those gammas by a photon counter. They can be used as simple counters in the thermal region and (simultaneously) as energy selector and counters for neutrons in the eV energy region. Several years of extensive development have made eV neutron spectrometers operating in the so-called resonance detector spectrometer (RDS) configuration outperform their conventional counterparts. In fact, the VESUVIO spectrometer, a flagship instrument at ISIS serving a continuous user programme for eV inelastic neutron spectroscopy measurements, is operating in the RDS configuration since 2007. In this review, we discuss the physical mechanism underlying the RDS configuration and the development of associated instrumentation. A few successful neutron scattering experiments that utilize the radiative capture counting techniques will be presented together with the potential of this technique for thermal neutron diffraction measurements. We also outline possible improvements and future perspectives for radiative capture based neutron detectors in neutron scattering application at pulsed neutron sources.

  17. Radiative neutron capture as a counting technique at pulsed spallation neutron sources: a review of current progress

    NASA Astrophysics Data System (ADS)

    Schooneveld, E. M.; Pietropaolo, A.; Andreani, C.; Perelli Cippo, E.; Rhodes, N. J.; Senesi, R.; Tardocchi, M.; Gorini, G.

    2016-09-01

    Neutron scattering techniques are attracting an increasing interest from scientists in various research fields, ranging from physics and chemistry to biology and archaeometry. The success of these neutron scattering applications is stimulated by the development of higher performance instrumentation. The development of new techniques and concepts, including radiative capture based neutron detection, is therefore a key issue to be addressed. Radiative capture based neutron detectors utilize the emission of prompt gamma rays after neutron absorption in a suitable isotope and the detection of those gammas by a photon counter. They can be used as simple counters in the thermal region and (simultaneously) as energy selector and counters for neutrons in the eV energy region. Several years of extensive development have made eV neutron spectrometers operating in the so-called resonance detector spectrometer (RDS) configuration outperform their conventional counterparts. In fact, the VESUVIO spectrometer, a flagship instrument at ISIS serving a continuous user programme for eV inelastic neutron spectroscopy measurements, is operating in the RDS configuration since 2007. In this review, we discuss the physical mechanism underlying the RDS configuration and the development of associated instrumentation. A few successful neutron scattering experiments that utilize the radiative capture counting techniques will be presented together with the potential of this technique for thermal neutron diffraction measurements. We also outline possible improvements and future perspectives for radiative capture based neutron detectors in neutron scattering application at pulsed neutron sources.

  18. Stellar neutron capture cross sections of the Ba isotopes

    NASA Astrophysics Data System (ADS)

    Voss, F.; Wisshak, K.; Guber, K.; Käppeler, F.; Reffo, G.

    1994-11-01

    The neutron capture cross sections of 134Ba, 135Ba, 136Ba, and 137Ba were measured in the energy range from 5 to 225 keV at the Karlsruhe 3.75 MV Van de Graaff accelerator. Neutrons were produced via the 7Li (p,n)7 Be reaction by bombarding metallic Li targets with a pulsed proton beam. Capture events were registered with the Karlsruhe 4π barium fluoride detector. The cross section ratios were determined with an overall uncertainty of ~3%, an improvement by factors of 5 to 8 compared to existing data. Severe discrepancies were found with respect to previous results. As a new possibility in time of flight experiments, isomeric cross section ratios could be determined for 135Ba, 136Ba, and 137Ba. Maxwellian averaged neutron capture cross sections were calculated for thermal energies between kT=10 keV and 100 keV. These stellar cross sections were used in an s-process analysis. For the s-only isotopes 134Ba and 136Ba the Ns<σ> ratio was determined to 0.875+/-0.025. Hence, a significant branching of the s-process path at 134Cs can be claimed for the first time, in contrast to predictions from the classical approach. This branching yields information on the s-process temperature, indicating values around T8=2. The new cross sections are also important for the interpretation of barium isotopic anomalies, which were recently discovered in SiC grains of carbonaceous chondrite meteorites. Together with the results from previous experiments on tellurium and samarium, a general improvement of the Ns<σ> systematics in the mass range A=120-150 is achieved. This yields a more reliable separation of s- and r-process contributions for comparison with stellar observations, but reveals a 20% discrepancy with respect to the solar barium abundance.

  19. Is (d,p{gamma}) a surrogate for neutron capture?

    SciTech Connect

    Hatarik, R.; Cizewski, J. A.; O'Malley, P. D.; Bernstein, L. A.; Burke, J. T.; Lesher, S. R.; Gibelin, J. D.; Phair, L. W.; Swan, T.

    2008-04-17

    To benchmark the validity of using the (d,p{gamma}) reaction as a surrogate for (n,{gamma}), the {sup 171,173}Yb(d,p{gamma}) reactions were measured and compared with the neutron capture cross sections measured by Wisshak et al. The (d,p{gamma}) ratios were measured using an 18.5 MeV deuteron beam from the 88-Inch Cyclotron at LBNL. Preliminary results comparing the surrogate ratios with the known (n,{gamma}) cross sections are discussed.

  20. Measurement of the 242Pu neutron capture cross section

    NASA Astrophysics Data System (ADS)

    Buckner, M. Q.; Wu, C. Y.; Henderson, R. A.; Bucher, B.; Bredeweg, T. A.; Baramsai, B.; Couture, A.; Jandel, M.; Mosby, S.; O'Donnell, J. M.; Ullmann, J. L.; Chyzh, A.; Dance Collaboration

    2015-10-01

    Precision (n,f) and (n, γ) cross sections are important for the network calculations of the radiochemical diagnostic chain for the U.S. DOE's Stockpile Stewardship Program. 242Pu(n, γ) cross section is relevant to the network calculations of Pu and Am. Additionally, new reactor concepts have catalyzed considerable interest in the measurement of improved cross sections for neutron-induced reactions on key actinides. To date, little or no experimental data has been reported on 242Pu(n, γ) for incident neutron energy below 50 keV. A new measurement of the 242Pu(n, γ) reaction was performed with the DANCE together with an improved PPAC for fission-fragment detection at LANSCE during FY14. The relative scale of the 242Pu(n, γ) cross section spans four orders of magnitude for incident neutron energies from thermal to ~ 30 keV. The absolute scale of the 242Pu(n, γ) cross section is set according to the measured 239Pu(n,f) resonance at 7.8 eV; the target was spiked with 239Pu for this measurement. The absolute 242Pu(n, γ) neutron capture cross section is ~ 30% higher than the cross section reported in ENDF for the 2.7 eV resonance. Latest results to be reported. Funded by U.S. DOE Contract No. DE-AC52-07NA27344 (LLNL) and DE-AC52-06NA25396 (LANL). U.S. DOE/NNSA Office of Defense Nuclear Nonproliferation Research and Development. Isotopes (ORNL).

  1. Borehole parametric study for neutron induced capture gamma-ray spectrometry using the MCNP code.

    PubMed

    Shahriari, M; Sohrabpour, M

    2000-01-01

    The MCNP Monte Carlo code has been used to simulate neutron transport from an Am-Be source into a granite formation surrounding a borehole. The effects of the moisture and the neutron poison on the thermal neutron flux distribution and the capture by the absorbing elements has been calculated. Thermal and nonthermal captures for certain absorbers having resonance structures in the epithermal and fast energy regions such as W and Si were performed. It is shown that for those absorbers having large resonances in the epithermal regions when they are present in dry formation or when accompanied by neutron poisons the resonance captures may be significant compared to the thermal captures.

  2. Neutron single particle structure in 131Sn and direct neutron capture cross sections

    SciTech Connect

    Kozub, R. L.; Arbanas, Goran; Adekola, A. S.; Bardayan, Daniel W; Blackmon, Jeffery C; Chae, Kyung Yuk; Chipps, K.; Cizewski, J. A.; Erikson, Luke; Hatarik, Robert; Hix, William Raphael; Jones, K. L.; Krolas, W.; Liang, J Felix; Ma, Z.; Matei, Catalin; Moazen, Brian; Nesaraja, Caroline D; Pain, Steven D; Shapira, Dan; ShrinerJr., J. F.; Smith, Michael Scott; Swan, T. P.

    2012-01-01

    Recent calculations suggest that the rate of neutron capture by 130Sn has a significant impact on late-time nucleosynthesis in the r-process. Direct capture into low-lying bound states is expected to be significant in neutron capture near the N=82 closed shell, so r- process reaction rates may be strongly impacted by the properties of neutron single particle states in this region. In order to investigate these properties, the (d, p) reaction has been studied in inverse kinematics using a 630 MeV beam of 130Sn (4.8 MeV/u) and a (CD2)n target. An array of Si strip detectors, including SIDAR and an early implementation of the ORRUBA, was used to detect reaction products. Results for the 130Sn(d, p)131Sn reaction are found to be very similar to those from the previously reported 132Sn(d, p)133Sn reaction. Direct-semidirect (n, ) cross section calculations, based for the first time on experimental data, are presented. The uncertainties in these cross sections are thus reduced by orders of magnitude from previous estimates.

  3. Continuum quasiparticle random-phase approximation for astrophysical direct neutron capture reactions on neutron-rich nuclei

    NASA Astrophysics Data System (ADS)

    Matsuo, Masayuki

    2015-03-01

    I formulate a many-body theory to calculate the cross section of direct radiative neutron capture reaction by means of the Hartree-Fock-Bogoliubov mean-field model and the continuum quasiparticle random-phase approximation (QRPA). A focus is put on very-neutron-rich nuclei and low-energy neutron kinetic energy in the range from 1 keV to several MeV, which is relevant to the rapid neutron capture process of nucleosynthesis. I begin with the photoabsorption cross section and the E 1 strength function. Next, in order to apply the reciprocity theorem, I decompose the cross section into partial cross sections corresponding to different channels of one- and two-neutron emission decays of photo-excited states. A numerical example is shown for the photo-absorption of 142Sn and the neutron capture of 141Sn .

  4. Uncertainties in Hauser-Feshbach Neutron Capture Calculations for Astrophysics

    SciTech Connect

    Bertolli, M.G. Kawano, T.; Little, H.

    2014-06-15

    The calculation of neutron capture cross sections in a statistical Hauser-Feshbach method has proved successful in numerous astrophysical applications. Of increasing interest is the uncertainty associated with the calculated Maxwellian averaged cross sections (MACS). Aspects of a statistical model that introduce a large amount of uncertainty are the level density model, γ-ray strength function parameter, and the placement of E{sub low} – the cut-off energy below which the Hauser-Feshbach method is not applicable. Utilizing the Los Alamos statistical model code CoH3 we investigate the appropriate treatment of these sources of uncertainty via systematics of nuclei in a local region for which experimental or evaluated data is available. In order to show the impact of uncertainty analysis on nuclear data for astrophysical applications, these new uncertainties will be propagated through the nucleosynthesis code NuGrid.

  5. Scissors mode of Gd nuclei studied from resonance neutron capture

    SciTech Connect

    Kroll, J.; Baramsai, B.; Becker, J. A.; and others

    2012-10-20

    Spectra of {gamma} rays following the neutron capture at isolated resonances of stable Gd nuclei were measured. The objectives were to get new information on photon strength of {sup 153,155-159}Gd with emphasis on the role of the M1 scissors-mode vibration. An analysis of the data obtained clearly indicates that the scissors mode is coupled not only to the ground state, but also to all excited levels of the nuclei studied. The specificity of our approach ensures unbiasedness in estimating the sumed scissors-mode strength {Sigma}B(M1){up_arrow}, even for odd product nuclei, for which conventional nuclear resonance fluorescence measurements yield only limited information. Our analysis indicates that for these nuclei the sum {Sigma}B(M1){up_arrow} increases with A and for {sup 157,159}Gd it is significantly higher compared to {sup 156,158}Gd.

  6. Neutron Capture Cross Section Calculations with the Statistical Model

    NASA Astrophysics Data System (ADS)

    Beard, Mary; Uberseder, Ethan; Wiescher, Michael

    2014-09-01

    Hauser-Feshbach (HF) cross sections are of enormous importance for a wide range of applications, from waste transmutation and nuclear technologies, to medical applications, and nuclear astrophysics. It is a well observed result that different nuclear input models sensitively affect HF cross section calculations. Less well-known however are the effects on calculations originating from model-specific implementation details (such as level density parameter, matching energy, backshift and giant dipole parameters), as well as effects from non-model aspects, such as experimental data truncation and transmission function energy binning. To investigate the effects or these various aspects, Maxwellian-averaged neutron capture cross sections have been calculated for approximately 340 nuclei. The relative effects of these model details will be discussed.

  7. Measurement of the neutron-neutron scattering length using the π-d capture reaction

    NASA Astrophysics Data System (ADS)

    Chen, Q.; Howell, C. R.; Carman, T. S.; Gibbs, W. R.; Gibson, B. F.; Hussein, A.; Kiser, M. R.; Mertens, G.; Moore, C. F.; Morris, C.; Obst, A.; Pasyuk, E.; Roper, C. D.; Salinas, F.; Setze, H. R.; Slaus, I.; Sterbenz, S.; Tornow, W.; Walter, R. L.; Whiteley, C. R.; Whitton, M.

    2008-05-01

    We have determined a value for the 1S0 neutron-neutron scattering length (ann) from high-precision measurements of time-of-flight spectra of neutrons from the H2(π-,nγ)n capture reaction. The measurements were done at the Los Alamos Meson Physics Facility by the E1286 Collaboration. The high spatial resolution of our γ-ray detector enabled us to make a detailed assessment of the systematic uncertainties in our techniques. The value obtained in the present work is ann=-18.63±0.10 (statistical) ± 0.44 (systematic) ± 0.30 (theoretical) fm. This result is consistent with previous determinations of ann from the π-d capture reaction. We found that the analysis of the data with calculations that use a relativistic phase-space factor gives a more negative value for ann by 0.33 fm over the analysis done using a nonrelativistic phase-space factor. Combining the present result with the previous ones from π-d capture gives ann=-18.63±0.27(expt)±0.30 fm (theory). For the first time the combined statistical and systematic experimental uncertainty in ann is smaller than the theoretical uncertainty and comparable to the uncertainty in the proton-proton 1S0 scattering length (app). This average value of ann when corrected for the magnetic-moment interaction of the two neutrons becomes -18.9 ± 0.4 fm, which is 1.6 ± 0.5 fm different from the recommended value of app, thereby confirming charge symmetry breaking at the 1% confidence level.

  8. 21 CFR 892.5300 - Medical neutron radiation therapy system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical neutron radiation therapy system. 892.5300... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5300 Medical neutron radiation therapy system. (a) Identification. A medical neutron radiation therapy system is a device intended...

  9. 21 CFR 892.5300 - Medical neutron radiation therapy system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Medical neutron radiation therapy system. 892.5300... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5300 Medical neutron radiation therapy system. (a) Identification. A medical neutron radiation therapy system is a device intended...

  10. 21 CFR 892.5300 - Medical neutron radiation therapy system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical neutron radiation therapy system. 892.5300... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5300 Medical neutron radiation therapy system. (a) Identification. A medical neutron radiation therapy system is a device intended...

  11. 21 CFR 892.5300 - Medical neutron radiation therapy system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical neutron radiation therapy system. 892.5300... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5300 Medical neutron radiation therapy system. (a) Identification. A medical neutron radiation therapy system is a device intended...

  12. 21 CFR 892.5300 - Medical neutron radiation therapy system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical neutron radiation therapy system. 892.5300... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5300 Medical neutron radiation therapy system. (a) Identification. A medical neutron radiation therapy system is a device intended...

  13. Fission, total and neutron capture cross section measurements at ORELA

    SciTech Connect

    Guber, K.H.; Spencer, R.R.; Leal, L.C.; Larson, D.C.; Dos Santos, G.; Harvey, J.A.; Hill, N.W.

    1998-08-01

    In support of the Nuclear Criticality Predictability Program established in response to the Defense Nuclear Facility Safety Board Recommendation 93-2, time-of-flight (TOF) measurements of the fission cross sections of {sup 233}U in the neutron energy range from 0.36 eV to several hundred keV have been initiated at the Oak Ridge Electron Linear Accelerator (ORELA). Also total and capture cross sections of Al, Cl, and K in the energy range from about 100 eV to several hundred keV have been measured or are under way. The goal is to derive accurate cross section representations for the materials involved in criticality calculations of fuel storage, transportation, etc., configurations. Additional high-resolution measurements of the total cross sections of {sup 233}U below a few keV neutron energy are being planned for 1998, as well as for the other involved material. Evaluated data files in ENDF-6 format will be processed into formats for use in criticality analysis and utilized in benchmark data testing. Finally the data will be submitted for inclusion in ENDF/B.

  14. First platinum moderated positron beam based on neutron capture

    NASA Astrophysics Data System (ADS)

    Hugenschmidt, C.; Kögel, G.; Repper, R.; Schreckenbach, K.; Sperr, P.; Triftshäuser, W.

    2002-12-01

    A positron beam based on absorption of high energy prompt γ-rays from thermal neutron capture in 113Cd was installed at a neutron guide of the high flux reactor at the ILL in Grenoble. Measurements were performed for various source geometries, dependent on converter mass, moderator surface and extraction voltages. The results lead to an optimised design of the in-pile positron source which will be implemented at the Munich research reactor FRM-II. The positron source consists of platinum foils acting as γ-e +e --converter and positron moderator. Due to the negative positron work function moderation in heated platinum leads to emission of monoenergetic positrons. The positron work function of polycrystalline platinum was determined to 1.95(5) eV. After acceleration to several keV by four electrical lenses the beam was magnetically guided in a solenoid field of 7.5 mT leading to a NaI-detector in order to detect the 511 keV γ-radiation of the annihilating positrons. The positron beam with a diameter of less than 20 mm yielded an intensity of 3.1×10 4 moderated positrons per second. The total moderation efficiency of the positron source was about ɛ=1.06(16)×10 -4. Within the first 20 h of operation a degradation of the moderation efficiency of 30% was observed. An annealing procedure at 873 K in air recovers the platinum moderator.

  15. Use of Neutron Transfer Reactions to Indirectly Determine Neutron Capture Cross Sections on Neutron-Rich Nuclei

    SciTech Connect

    McCleskey, M.; Mukhamedzhanov, A. M.; Tribble, R. E.; Simmons, E.; Spiridon, A.; Banu, A.; Roeder, B.; Goldberg, V.; Trache, L.; Chen, X. F.; Lui, Y.-W.

    2010-03-01

    {sup 14}C(n,gamma){sup 15}C is being used as a test case in the development of an indirect method to determine neutron capture cross sections on neutron-rich unstable nuclei at astrophysical energies. Our approach makes use of two reactions: one peripheral used to find the asymptotic normalization coefficient (ANC) and a second non-peripheral reaction to determine the spectroscopic factor. The ANC for {sup 15}C has been determined using a HI neutron transfer reaction with a 12 MeV/nucleon {sup 14}C beam on a {sup 13}C target. The spectroscopic factor will be determined using {sup 14}C(d,p) in forward kinematics with an incident deuteron energy of 60 MeV. Both experiments were performed using the MDM high-resolution spectrometer at Texas A and M University.

  16. SIMS ion microscopy imaging of boronophenylalanine (BPA) and 13C15N-labeled phenylalanine in human glioblastoma cells: Relevance of subcellular scale observations to BPA-mediated boron neutron capture therapy of cancer

    NASA Astrophysics Data System (ADS)

    Chandra, Subhash; Lorey, Daniel R., II

    2007-02-01

    p-Boronophenylalanine (BPA) is a clinically approved boron neutron capture therapy (BNCT) agent currently being used in clinical trials of glioblastoma multiforme, melanoma and liver metastases. Secondary ion mass spectrometry (SIMS) observations from the Cornell SIMS Laboratory provided support for using a 6 h infusion of BPA, instead of a 2 h infusion, for achieving higher levels of boron in brain tumor cells. These observations were clinically implemented in Phase II experimental trials of glioblastoma multiforme in Sweden. However, the mechanisms for higher BPA accumulation with longer infusions have remained unknown. In this work, by using 13C15N-labeled phenylalanine and T98G human glioblastoma cells, comparisons between the 10B-delivery of BPA and the accumulation of labeled phenylalanine after 2 and 6 h treatments were made with a Cameca IMS-3f SIMS ion microscope at 500 nm spatial resolution in fast frozen, freeze-fractured, freeze-dried cells. Due to the presence of the Na-K-ATPase in the plasma membrane of most mammalian cells, the cells maintain an approximately 10/1 ratio of K/Na in the intracellular milieu. Therefore, the quantitative imaging of these highly diffusible species in the identical cell in which the boron or labeled amino acid was imaged provides a rule-of-thumb criterion for validation of SIMS observations and the reliability of the cryogenic sampling. The labeled phenylalanine was detected at mass 28, as the 28(13C15N)- molecular ion. Correlative analysis with optical and confocal laser scanning microscopy revealed that fractured freeze-dried glioblastoma cells contained well-preserved ultrastructural details with three discernible subcellular regions: a nucleus or multiple nuclei, a mitochondria-rich perinuclear cytoplasmic region and the remaining cytoplasm. SIMS analysis revealed that the overall cellular signals of both 10B from BPA and 28CN- from labeled phenylalanine increased approximately 1.6-fold between the 2 and 6 h exposures

  17. Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: radiobiological studies at RA-1 Nuclear Reactor in a model of antigen-induced arthritis in rabbits.

    PubMed

    Trivillin, Verónica A; Bruno, Leandro J; Gatti, David A; Stur, Mariela; Garabalino, Marcela A; Hughes, Andrea Monti; Castillo, Jorge; Pozzi, Emiliano C C; Wentzeis, Luis; Scolari, Hugo; Schwint, Amanda E; Feldman, Sara

    2016-11-01

    Rheumatoid arthritis is a chronic autoimmune pathology characterized by the proliferation and inflammation of the synovium. Boron neutron capture synovectomy (BNCS), a binary treatment modality that combines the preferential incorporation of boron carriers to target tissue and neutron irradiation, was proposed to treat the pathological synovium in arthritis. In a previous biodistribution study, we showed the incorporation of therapeutically useful boron concentrations to the pathological synovium in a model of antigen-induced arthritis (AIA) in rabbits, employing two boron compounds approved for their use in humans, i.e., decahydrodecaborate (GB-10) and boronophenylalanine (BPA). The aim of the present study was to perform low-dose BNCS studies at the RA-1 Nuclear Reactor in the same model. Neutron irradiation was performed post intra-articular administration of BPA or GB-10 to deliver 2.4 or 3.9 Gy, respectively, to synovium (BNCS-AIA). AIA and healthy animals (no AIA) were used as controls. The animals were followed clinically for 2 months. At that time, biochemical, magnetic resonance imaging (MRI) and histological studies were performed. BNCS-AIA animals did not show any toxic effects, swelling or pain on palpation. In BNCS-AIA, the post-treatment levels of TNF-α decreased in four of six rabbits and IFN-γ levels decreased in five of six rabbits. In all cases, MRI images of the knee joint in BNCS-AIA resembled those of no AIA, with no necrosis or periarticular effusion. Synovial membranes of BNCS-AIA were histologically similar to no AIA. BPA-BNCS and GB-10-BNCS, even at low doses, would be therapeutically useful for the local treatment of rheumatoid arthritis.

  18. Production of heavy and superheavy neutron-rich nuclei in neutron capture processes

    NASA Astrophysics Data System (ADS)

    Zagrebaev, V. I.; Karpov, A. V.; Mishustin, I. N.; Greiner, Walter

    2011-10-01

    The neutron capture process is considered as an alternative method for production of superheavy (SH) nuclei. Strong neutron fluxes might be provided by nuclear reactors and nuclear explosions in the laboratory frame and by supernova explosions in nature. All these cases are discussed in the paper. There are two gaps of short-lived nuclei (one is the well-known fermium gap and the other one is located in the region of Z=106-108 and N˜170) which impede the formation of SH nuclei by rather weak neutron fluxes realized at available nuclear reactors. We find that in the course of multiple (rather “soft”) nuclear explosions these gaps may be easily bypassed, and thus, a measurable amount of the neutron-rich long-living SH nuclei located at the island of stability may be synthesized. Existing pulsed reactors do not allow one to bypass these gaps. We formulate requirements for the pulsed reactors of the next generation that could be used for production of long-living SH nuclei. Natural formation of SH nuclei (in supernova explosions) is also discussed. The yield of SH nuclei relative to lead is estimated to be about 10-12, which is not beyond the experimental sensitivity for a search of SH elements in cosmic rays.

  19. Muon capture on the deuteron and the neutron-neutron scattering length

    NASA Astrophysics Data System (ADS)

    Marcucci, L. E.; Machleidt, R.

    2014-11-01

    Background: We consider the muon capture reaction μ-+2H→νμ+n +n , which presents a "clean" two-neutron (n n ) system in the final state. We study here its capture rate in the doublet hyperfine initial state (ΓD). The total capture rate for the muon capture μ-+3He→νμ+3H (Γ0) is also analyzed, although, in this case, the n n system is not so clean anymore. Purpose: We investigate whether ΓD (and Γ0) could be sensitive to the n n S -wave scattering length (an n), and we check on the possibility to extract an n from an accurate measurement of ΓD. Method: The muon capture reactions are studied with nuclear potentials and charge-changing weak currents, derived within chiral effective field theory. The next-to-next-to-next-to-leading-order chiral potential with cutoff parameter Λ =500 MeV is used, but the low-energy constant (LEC) determining an n is varied so as to obtain an n=-18.95 ,-16.0 ,-22.0 , and +18.22 fm. The first value is the present empirical one, while the last one is chosen such as to lead to a di-neutron bound system with a binding energy of 139 keV. The LEC's cD and cE, present in the three-nucleon potential and axial-vector current (cD), are constrained to reproduce the A =3 binding energies and the triton Gamow-Teller matrix element. Results: The capture rate ΓD is found to be 399 (3 ) s-1 for an n=-18.95 and -16.0 fm; and 400 (3 ) s-1 for an n=-22.0 fm. However, in the case of an n=+18.22 fm, the result of 275 (3 ) s-1 [ 135 (3 ) s-1 ] is obtained, when the di-neutron system in the final state is unbound (bound). The total capture rate Γ0 for muon capture on 3He is found to be 1494(15), 1491(16), 1488(18), and 1475(16) s-1 for an n=-18.95 ,-16.0 ,-22.0 , and +18.22 fm, respectively. All the theoretical uncertainties are due to the fitting procedure and radiative corrections. Conclusions: Our results seem to exclude the possibility of constraining a negative an n with an uncertainty of less than ˜±3 fm through an accurate

  20. The Detector for Advanced Neutron Capture Experiments: A 4{pi} BaF2 Detector for Neutron Capture Measurements at LANSCE

    SciTech Connect

    Ullmann, J.L.; Esch, E.-I.; Haight, R.C.; Hunt, L.; O'Donnell, J.M.; Reifarth, R.; Agvaanluvsan, U.; Alpizar, A.; Hatarik, R.; Bond, E.M.; Bredeweg, T.A.; Kronenberg, A.; Rundberg, R.S.; Vieira, D.J.; Wilhelmy, J.B.; Folden, C.M.; Hoffman, D.C.; Greife, U.; Schwantes, J.M.; Strottman, D.D.

    2005-05-24

    The Detector for Advanced Neutron Capture Experiments (DANCE) is a 162-element 4{pi} BaF2 array designed to make neutron capture cross-section measurements on rare or radioactive targets with masses as little as one milligram. Accurate capture cross sections are needed in many research areas, including stellar nucleosynthesis, advanced nuclear fuel cycles, waste transmutation, and other applied programs. These cross sections are difficult to calculate accurately and must be measured. The design and initial performance results of DANCE is discussed.

  1. 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.

  2. Multigroup neutron dose calculations for proton therapy

    SciTech Connect

    Kelsey Iv, Charles T; Prinja, Anil K

    2009-01-01

    We have developed tools for the preparation of coupled multigroup proton/neutron cross section libraries. Our method is to use NJOY to process evaluated nuclear data files for incident particles below 150 MeV and MCNPX to produce data for higher energies. We modified the XSEX3 program of the MCNPX code system to produce Legendre expansions of scattering matrices generated by sampling the physics models that are comparable to the output of the GROUPR routine of NJOY. Our code combines the low and high energy scattering data with user input stopping powers and energy deposition cross sections that we also calculated using MCNPX. Our code also calculates momentum transfer coefficients for the library and optionally applies an energy straggling model to the scattering cross sections and stopping powers. The motivation was initially for deterministic solution of space radiation shielding calculations using Attila, but noting that proton therapy treatment planning may neglect secondary neutron dose assessments because of difficulty and expense, we have also investigated the feasibility of multi group methods for this application. We have shown that multigroup MCNPX solutions for secondary neutron dose compare well with continuous energy solutions and are obtainable with less than half computational cost. This efficiency comparison neglects the cost of preparing the library data, but this becomes negligible when distributed over many multi group calculations. Our deterministic calculations illustrate recognized obstacles that may have to be overcome before discrete ordinates methods can be efficient alternatives for proton therapy neutron dose calculations.

  3. Radioactivity induced by neutrons: Enrico Fermi and a thermodynamic approach to radiative capture

    NASA Astrophysics Data System (ADS)

    De Gregorio, Alberto

    2006-07-01

    When Fermi learned that slow neutrons are much more effective than fast ones in inducing radioactivity, he explained this phenomenon by mentioning the well-known scattering cross section between neutrons and protons. At this early stage, he did not refer to the capture cross section by target nuclei. At the same time a thermodynamic approach to neutron-proton capture was being discussed by physicists: neutron capture was interpretated as the reverse of deuteron photodissociation and detailed balance among neutrons, protons, deuterons, and radiation was invoked. This thermodynamic approach might underlie Fermi's early explanation of the great efficiency of slow neutrons. Fermi repeatedly used a thermodynamic approach that had been used in describing some of the physical properties of conductors by Richardson and had been influential in Fermi's youth.

  4. Pancreatic carcinoma: results with fast neutron therapy

    SciTech Connect

    Kaul, R.; Cohen, L.; Hendrickson, F.; Awschalom, M.; Hrejsa, A.F.; Rosenberg, I.

    1981-02-01

    Results of therapy in 31 of 50 patients who were treated for advanced pancreatic carcinoma at Fermi National Accelerator Laboratory are presented here. To date, six patients are alive and four are free of disease. Since the main reason for failure was lack of control of primary tumor, the tumor dose has been increased by 15%. Based on our results, a nationwide study has been launched to assess the effectiveness of neutrons vs photons in the treatment of locally advanced pancreatic carcinoma.

  5. Microdosimetric investigations at the Fast Neutron Therapy Facility at Fermilab

    SciTech Connect

    Langen, Katja Maria

    1997-01-01

    Microdosimetry was used to investigate three issues at the neutron therapy facility (NTF) at Fermilab. Firstly, the conversion factor from absorbed dose in A-150 tissue equivalent plastic to absorbed dose in ICRU tissue was determined. For this, the effective neutron kerma factor ratios, i.e. oxygen tissue equivalent plastic and carbon to A-150 tissue equivalent plastic, were measured in the neutron beam. An A-150 tissue equivalent plastic to ICRU tissue absorbed dose conversion factor of 0.92 ± 0.04 determined. Secondly, variations in the radiobiological effectiveness (RBE) in the beam were mapped by determining variations in two related quantities, e* and R, with field size and depth in tissue. Maximal variation in e* and R of 9% and 15% respectively were determined. Lastly, the feasibility of utilizing the boron neutron capture reaction on boron-10 to selectively enhance the tumor dose in the NTF beam was investigated. In the unmodified beam, a negligible enhancement for a 50 ppm boron loading was measured. To boost the boron dose enhancement to 3% it was necessary to change the primary proton energy from 66 MeV and to filter the beam by 90 mm of tungsten.

  6. Gamma spectrum following neutron capture in {sup 167}Er

    SciTech Connect

    Visser, D.; Khoo, T.L.; Lister, C.J.

    1995-08-01

    Statistical decay from a highly excited state samples all the lower-lying states and, hence, provides a sensitive measure of the level density. Pairing has a major impact on the level density, e.g. creating a pair gap between the 0- and 2-quasiparticle configurations. Hence the shape of the statistical spectrum contains information on pairing, and can be used to provide information on the reduction of pairing with thermal excitation energy. For this reason, we measured the complete spectrum of {gamma}rays following thermal neutron capture in {sup 167}Er. The experiment was performed at the Brookhaven reactor using Compton-suppressed Ge detectors from TESSA. The spectrum, which was corrected for detector response and efficiency, reveals primary (first-step, high-energy) transitions up to nearly 8 MeV, secondary (last-step, lower-energy) transitions, as we as a continuous statistical component. Effort was expanded to identify all lines from contaminant sources and an upper limit of 5% was tentatively set for their contributions. The spectral shape of the statistical spectrum will be compared with theoretical spectra obtained from a calculation of pairing which accounts for a stepwise reduction of the pair correlations as the number of quasiparticles increases. The primary lines which decay directly to the near-yrast states will also be used to deduce the level densities.

  7. Neutron Capture Cross Section Measurement on $^{238}$Pu at DANCE

    SciTech Connect

    Chyzh, A; Wu, C Y

    2011-02-14

    The proposed neutron capture measurement for {sup 238}Pu was carried out in Nov-Dec, 2010, using the DANCE array at LANSCE, LANL. The total beam-on-target time is about 14 days plus additional 5 days for the background measurement. The target was prepared at LLNL with the new electrplating cell capable of plating the {sup 238}Pu isotope simultaneously on both sides of the 3-{micro}m thick Ti backing foil. A total mass of 395 {micro}g with an activity of 6.8 mCi was deposited onto the area of 7 mm in diameter. The {sup 238}Pu sample was enriched to 99.35%. The target was covered by 1.4 {micro}m double-side aluminized mylar and then inserted into a specially designed vacuum-tight container, shown in Fig. 1, for the {sup 238}Pu containment. The container was tested for leaks in the vacuum chamber at LLNL. An identical container without {sup 238}Pu was made as well and used as a blank for the background measurement.

  8. Neutron Capture and Neutron Total Cross Sections Measurements for {sup 27}Al at the Oak Ridge Electron Linear Accelerator

    SciTech Connect

    Guber, K.H.; Harvey, J.A.; Hill, N.W.; Koehler, P.E.; Leal, L.C.; Sayer, R.O.; Spencer, R.R.; Wright, R.Q.

    1999-08-30

    We have used the Oak Ridge Electron Linear Accelerator (ORELA) to measure neutron total and capture cross sections of {sup 27}Al in the energy range from 100 eV to {approximately}400 keV. We report the resonance parameters as well as the Maxwellian average capture cross sections.

  9. Recent Research with the Detector for Advanced Neutron Capture Experiments (dance) at the LOS Alamos Neutron Science Center

    NASA Astrophysics Data System (ADS)

    Ullmann, J. L.

    2014-09-01

    The DANCE detector at Los Alamos is a 160 element, nearly 4π BaF2 detector array designed to make measurements of neutron capture on rare or radioactive nuclides. It has also been used to make measurements of gamma-ray multiplicity following capture and gamma-ray output from fission. Several examples of measurements are briefly discussed.

  10. DANCE : a 4[pi] barium fluoride detector for measuring neutron capture on unstable nuclei /.

    SciTech Connect

    Ullmann, J. L.; Haight, Robert C.; Hunt, L. F.; Reifarth, R.; Rundberg, R. S.; Bredeweg, T. A.; Fowler, Malcolm M.; Miller, G. G.; Heil, M.; Käppeler, F.; Chamberlin, E. P.

    2002-01-01

    Measurements of neutron capture on unstable nuclei are important for studies of s-process nucleosynthesis, nuclear waste transmutation, and stewardship science. A 160-element, 4{pi} barium fluoride detector array, and associated neutron flight path, is being constructed to make capture measurements at the moderated neutron spallation source at LANSCE. Measurements can be made on as little as 1 mg of sample material over energies from near thermal to near 100 keV. The design of the DANCE array is described and neutron flux measurements from flight path commissioning are shown. The array is expected to be complete by the end of 2002.

  11. Capture-gated Spectroscopic Measurements of Monoenergetic Neutrons with a Composite Scintillation Detector

    SciTech Connect

    Nattress, Jason; Mayer, M.; Foster, A.; Barhoumi Meddeb, A.; Trivelpiece, C.; Ounaies, Z.; Jovanovic, I.

    2016-04-01

    Abstract—We report on the measurements of Monoenergetic neutrons from DD and DT fusion reactions by use of the capture gating method in a heterogeneous plastic-glass composite scintillation detector. The cylindrical detector is 5.08 cm in diameter and 5.05 cm in height and was fabricated using 1-mm diameter Li-doped glass rods(GS20) and scintillating polyvinyl toluene (EJ-290). Different scintillation decay constants are used to identify energy depositions in two materials constituting the composite scintillator. Geant4 simulations of the neutron thermalization and capture process were conducted, finding a mean capture time of approximately 2.6 ms for both DD and DT neutrons. A capture gating time acceptance window based on simulation results was used to identify the neutron thermalization pulses. The total scintillation light yield produced in neutron thermalization was measured and found to show consistency on event-by-event basis despite the variety of neutron thermalization histories prior to capture. The ratio of light yields from thermalization of 14.1 MeV and 2.45 MeV neutrons in the EJ-290 scintillator was determined to be 14.6, and the light output from 2.45 MeV neutrons was also correlated to its electron equivalent, obtaining a value of 0.58*0.05 MeVee.

  12. Exploration of direct neutron capture with covariant density functional theory inputs

    NASA Astrophysics Data System (ADS)

    Zhang, Shi-Sheng; Peng, Jin-Peng; Smith, M. S.; Arbanas, G.; Kozub, R. L.

    2015-04-01

    Predictions of direct neutron capture are of vital importance for simulations of nucleosynthesis in supernovae, merging neutron stars, and other astrophysical environments. We calculated direct capture cross sections using nuclear structure information obtained from a covariant density functional theory as input for the fresco coupled reaction channels code. We investigated the impact of pairing, spectroscopic factors, and optical potentials on our results to determine a robust method to calculate cross sections of direct neutron capture on exotic nuclei. Our predictions agree reasonably well with experimental cross section data for the closed shell nuclei 16O and 48Ca, and for the exotic nucleus 36S . We then used this approach to calculate the direct neutron capture cross section on the doubly magic unstable nucleus 132Sn which is of interest for the astrophysical r-process.

  13. Dose evaluation of boron neutron capture synovectomy using the THOR epithermal neutron beam: a feasibility study

    NASA Astrophysics Data System (ADS)

    Wu, Jay; Chang, Shu-Jun; Chuang, Keh-Shih; Hsueh, Yen-Wan; Yeh, Kuan-Chuan; Wang, Jeng-Ning; Tsai, Wen-Pin

    2007-03-01

    Rheumatoid arthritis is one of the most common epidemic diseases in the world. For some patients, the treatment with steroids or nonsteroidal anti-inflammatory drugs is not effective, thus necessitating physical removal of the inflamed synovium. Alternative approaches other than surgery will provide appropriate disease control and improve the patient's quality of life. In this research, we evaluated the feasibility of conducting boron neutron capture synovectomy (BNCS) with the Tsing Hua open-pool reactor (THOR) as a neutron source. Monte Carlo simulations were performed with arthritic joint models and uncertainties were within 5%. The collimator, reflector and boron concentration were optimized to reduce the treatment time and normal tissue doses. For the knee joint, polyethylene with 40%-enriched Li2CO3 was used as the collimator material, and a rear reflector of 15 cm thick graphite and side reflector of 10 cm thick graphite were chosen. The optimized treatment time was 5.4 min for the parallel-opposed irradiation. For the finger joint, polymethyl methacrylate was used as the reflector material. The treatment time can be reduced to 3.1 min, while skin and bone doses can be effectively reduced by approximately 9% compared with treatment using the graphite reflector. We conclude that using THOR as a treatment modality for BNCS could be a feasible alternative in clinical practice.

  14. Neutron capture measurement on {sup 173}Lu at LANSCE with DANCE detector

    SciTech Connect

    Theroine, C.; Ebran, A.; Meot, V.; Roig, O.; Bond, E. M.; Bredeweg, T. A.; Couture, A.; Haight, R. C.; Jandel, M.; Nortier, F. M.; O'Donnell, J. M.; Rundberg, R. S.; Taylor, W. A.; Ullmann, J. L.; Viera, D. J.; Wilhelmy, J. B.; Wouters, J. M.

    2013-06-10

    The (n,{gamma}) cross section on the unstable {sup 173}Lu(t{sub 1/2} = 1.37y) has been measured from thermal energy up to 200 eV at Los Alamos Neutron Science Center (LANSCE) with The Detector for Advanced Neutron Capture Experiements (DANCE). The main aim of this study is to validate and optimize reaction models for unstable nucleus. A preliminary capture yield will be presented in this paper.

  15. The Ubiquity of the Rapid Neutron-capture Process

    NASA Astrophysics Data System (ADS)

    Roederer, Ian U.; Cowan, John J.; Karakas, Amanda I.; Kratz, Karl-Ludwig; Lugaro, Maria; Simmerer, Jennifer; Farouqi, Khalil; Sneden, Christopher

    2010-12-01

    To better characterize the abundance patterns produced by the r-process, we have derived new abundances or upper limits for the heavy elements zinc (Zn, Z= 30), yttrium (Y, Z= 39), lanthanum (La, Z= 57), europium (Eu, Z= 63), and lead (Pb, Z= 82). Our sample of 161 metal-poor stars includes new measurements from 88 high-resolution and high signal-to-noise spectra obtained with the Tull Spectrograph on the 2.7 m Smith Telescope at the McDonald Observatory, and other abundances are adopted from the literature. We use models of the s-process in asymptotic giant branch stars to characterize the high Pb/Eu ratios produced in the s-process at low metallicity, and our new observations then allow us to identify a sample of stars with no detectable s-process material. In these stars, we find no significant increase in the Pb/Eu ratios with increasing metallicity. This suggests that s-process material was not widely dispersed until the overall Galactic metallicity grew considerably, perhaps even as high as [Fe/H] =-1.4, in contrast with earlier studies that suggested a much lower mean metallicity. We identify a dispersion of at least 0.5 dex in [La/Eu] in metal-poor stars with [Eu/Fe] <+0.6 attributable to the r-process, suggesting that there is no unique "pure" r-process elemental ratio among pairs of rare earth elements. We confirm earlier detections of an anti-correlation between Y/Eu and Eu/Fe bookended by stars strongly enriched in the r-process (e.g., CS 22892-052) and those with deficiencies of the heavy elements (e.g., HD 122563). We can reproduce the range of Y/Eu ratios using simulations of high-entropy neutrino winds of core-collapse supernovae that include charged-particle and neutron-capture components of r-process nucleosynthesis. The heavy element abundance patterns in most metal-poor stars do not resemble that of CS 22892-052, but the presence of heavy elements such as Ba in nearly all metal-poor stars without s-process enrichment suggests that the r

  16. THE UBIQUITY OF THE RAPID NEUTRON-CAPTURE PROCESS

    SciTech Connect

    Roederer, Ian U.; Sneden, Christopher; Cowan, John J.; Karakas, Amanda I.; Kratz, Karl-Ludwig; Lugaro, Maria; Simmerer, Jennifer; Farouqi, Khalil

    2010-12-01

    To better characterize the abundance patterns produced by the r-process, we have derived new abundances or upper limits for the heavy elements zinc (Zn, Z= 30), yttrium (Y, Z= 39), lanthanum (La, Z= 57), europium (Eu, Z= 63), and lead (Pb, Z= 82). Our sample of 161 metal-poor stars includes new measurements from 88 high-resolution and high signal-to-noise spectra obtained with the Tull Spectrograph on the 2.7 m Smith Telescope at the McDonald Observatory, and other abundances are adopted from the literature. We use models of the s-process in asymptotic giant branch stars to characterize the high Pb/Eu ratios produced in the s-process at low metallicity, and our new observations then allow us to identify a sample of stars with no detectable s-process material. In these stars, we find no significant increase in the Pb/Eu ratios with increasing metallicity. This suggests that s-process material was not widely dispersed until the overall Galactic metallicity grew considerably, perhaps even as high as [Fe/H] =-1.4, in contrast with earlier studies that suggested a much lower mean metallicity. We identify a dispersion of at least 0.5 dex in [La/Eu] in metal-poor stars with [Eu/Fe] <+0.6 attributable to the r-process, suggesting that there is no unique 'pure' r-process elemental ratio among pairs of rare earth elements. We confirm earlier detections of an anti-correlation between Y/Eu and Eu/Fe bookended by stars strongly enriched in the r-process (e.g., CS 22892-052) and those with deficiencies of the heavy elements (e.g., HD 122563). We can reproduce the range of Y/Eu ratios using simulations of high-entropy neutrino winds of core-collapse supernovae that include charged-particle and neutron-capture components of r-process nucleosynthesis. The heavy element abundance patterns in most metal-poor stars do not resemble that of CS 22892-052, but the presence of heavy elements such as Ba in nearly all metal-poor stars without s-process enrichment suggests that the r

  17. Gamma-Ray Strength Function Method:. Away from Photoneutron Emission to Radiative Neutron Capture

    NASA Astrophysics Data System (ADS)

    Utsunomiya, H.; Akimune, H.; Yamagata, T.; Iwamoto, C.; Goriely, S.; Daoutidis, I.; Toyokawa, H.; Harada, H.; Kitatani, F.; Iwamoto, N.; Lui, Y. W.; Arteaga, D. P.; Hilaire, S.; Koning, A. J.

    2013-03-01

    Radiative neutron capture cross sections are of direct relevance for the synthesis of heavy elements referred to as the s-process and the r-process in nuclear astrophysics and constitute basic data in the field of nuclear engineering. The surrogate reaction technique is in active use to indirectly determine radiative neutron capture cross sections for unstable nuclei. We have devised an indirect method alternative to the surrogate reaction technique on the basis of the γ-ray strength function (γSF), a nuclear statistical quantity that interconnects photoneutron emission and radiative neutron capture in the Hauser-Feshbach model calculation. We outline the γSF method and show applications of the method to tin, palladium, and zirconium isotopes. In the application of the γSF method, it is important to use γSF's that incorporate extra strengths of PDR and/or M1 resonance emerging around neutron threshold.

  18. Thermal neutron capture cross section for the K isomer {sup 177}Lu{sup m}

    SciTech Connect

    Belier, G.; Roig, O.; Daugas, J.-M.; Giarmana, O.; Meot, V.; Letourneau, A.; Marie, F.; Foucher, Y.; Aupiais, J.; Abt, D.; Jutier, Ch.; Le Petit, G.; Bettoni, C.; Gaudry, A.; Veyssiere, Ch.; Barat, E.; Dautremer, T.; Trama, J.-Ch.

    2006-01-15

    The thermal neutron radiative capture cross section for the K isomeric state in {sup 177}Lu has been measured for the first time. Several {sup 177}Lu{sup m} targets have been prepared and irradiated in various neutron fluxes at the Lauee Langevin Institute in Grenoble and at the CEA reactors OSIRIS and ORPHEE in Saclay. The method consists of measuring the {sup 178}Lu activity by {gamma}-ray spectroscopy. The values obtained in four different neutron spectra have been used to calculate the resonance integral of the radiative capture cross section for {sup 177}Lu{sup m}. In addition, an indirect method leads to the determination of the {sup 177}Lu{sup g} neutron radiative capture cross section.

  19. Measurement of Neutron Capture Cross Section of 62Ni in the keV-Region

    SciTech Connect

    Alpizar-Vicente, A. M.; Hatarik, R.; Bredeweg, T. A.; Esch, E.-I.; Haight, R. C.; O'Donnell, J. M.; Reifarth, R.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wilhelmy, J. B.; Wouters, J. M.; Greife, U.

    2006-03-13

    The neutron capture cross section of 62Ni, relative to gold as a standard, was determined in the energy range from 250 eV to 100 keV. This energy range covers the region between 5 keV to 20 keV, which is not available in ENDF. Capture events are detected with the 160-fold 4{pi} BaF2 Detector for Advanced Neutron Capture Experiments (DANCE) at the Los Alamos Neutron Science Center. One of the challenges was to process the high count rate of 4 MHz, which required an optimization of the data acquisition software. The neutron energy was determined by the time-of-flight technique using a flight path of 20.25 m. The sample mass of the 96% enriched 62Ni target was 210 mg and it was mounted in a 1.5 {mu}m thick Mylar foil.

  20. Investigation of the Statistical Properties of Stable Eu Nuclei using Neutron-Capture Reactions

    SciTech Connect

    Agvaanluvsan, U; Alpizar-Vicente, A; Becker, J A; Becvar, F; Bredeweg, T A; Clement, R; Esch, E; Folden, III, C M; Hatarik, R; Haight, R C; Hoffman, D C; Krticka, M; Macri, R A; Mitchell, G E; Nitsche, H; O'Donnell, J M; Parker, W; Reifarth, R; Rundberg, R S; Schwantes, J M; Sheets, S A; Ullmann, J L; Vieira, D J; Wilhelmy, J B; Wilk, P; Wouters, J M; Wu, C Y

    2005-10-04

    Neutron capture for incident neutron energies <1eV up to 100 keV has been measured for {sup 151,153}Eu targets. The highly efficient DANCE (Detector for Advanced Neutron Capture Experiments) array coupled with the intense neutro