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Sample records for capture therapy field

  1. 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. PMID:18196797

  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. Neutron capture therapies

    DOEpatents

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

    1999-01-01

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

  4. 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

  5. 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

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

    PubMed

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

    2015-03-01

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

  7. Advances in Neutron Capture Therapy

    SciTech Connect

    Soloway, A.H.; Barth, R.F.; Carpenter, D.E.

    1993-12-31

    This volume contains the proceedings of the Fifth International Symposium on Neutron Capture Therapy held September 14--17, 1992 in Columbus, Ohio. Individual papers were separately abstracted and indexed for the database.

  8. Mixed field dosimetry of epithermal neutron beams for boron neutron capture therapy at the MITR-II research reactor.

    PubMed

    Rogus, R D; Harling, O K; Yanch, J C

    1994-10-01

    During the past several years, there has been growing interest in Boron Neutron Capture Therapy (BNCT) using epithermal neutron beams. The dosimetry of these beams is challenging. The incident beam is comprised mostly of epithermal neutrons, but there is some contamination from photons and fast neutrons. Within the patient, the neutron spectrum changes rapidly as the incident epithermal neutrons scatter and thermalize, and a photon field is generated from neutron capture in hydrogen. In this paper, a method to determine the doses from thermal and fast neutrons, photons, and the B-10(n, alpha)Li-7 reaction is presented. The photon and fast neutron doses are measured with ionization chambers, in realistic phantoms, using the dual chamber technique. The thermal neutron flux is measured with gold foils using the cadmium difference technique, the thermal neutron and B-10 doses are determined by the kerma factor method. Representative results are presented for a unilateral irradiation of the head. Sources of error in the method as applied to BNCT dosimetry, and the uncertainties in the calculated doses are discussed.

  9. Microdosimetry of neutron field for boron neutron capture therapy at Kyoto university reactor.

    PubMed

    Endo, S; Onizuka, Y; Ishikawa, M; Takada, M; Sakurai, Y; Kobayashi, T; Tanaka, K; Hoshi, M; Shizuma, K

    2004-01-01

    Microdosimetric single event spectrum in a human body simulated by an acrylic phantom has been measured for the clinical BNCT field at the Kyoto University Reactor (KUR). The recoil particles resulting from the initial reaction and subsequent interactions, namely protons, electrons, alpha particles and carbon nuclei are identified in the microdosimetric spectrum. The relative contributions to the neutron dose from proton, alpha particles and carbon are estimated to be about 0.9, 0.07 and 0.3, respectively, four depths between 5 and 41 mm. We estimate that the dose averaged lineal energy, yD decreased with depth from 64 to 46 keV microm(-1). Relative biological effectiveness (RBE) of this neutron field using a response function for the microdosimetric spectrum was estimated to decrease from 3.6 to 2.9 with increasing depth. PMID:15353723

  10. Boron-neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Haque, A. M.; Moschini, G.; Valkovic, Vlado; Zafiropoulos, D.

    1995-03-01

    The final goal of any radiotherapy project is to expose the tumor as the target to a lethal dose of ionizing radiation, sparing thereby the surrounding healthy tissues to a maximum extent. Precise treatment is nevertheless essential for cure, since the danger exists that the tumor might re-establish itself if every cancer cell is not destroyed. The conventional therapy treatments existing to date, e.g., surgery, radiation therapy, and chemotherapy, have been successful in curing some kinds of cancers, but still there are many exceptions. In the following, the progress of a promising therapy tool, called the boron neutron capture therapy (BNCT), which has made its dynamic evolution in recent years, is briefly described. The approach towards clinical trials with BNCT is described in detail.

  11. 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.

  12. 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.

  13. 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.

  14. Spectrum evaluation at the filter-modified neutron irradiation field for neutron capture therapy in Kyoto University Research Reactor

    NASA Astrophysics Data System (ADS)

    Sakurai, Yoshinori; Kobayashi, Tooru

    2004-10-01

    The Heavy Water Neutron Irradiation Facility of the Kyoto University Research Reactor (KUR-HWNIF) was updated in March 1996, mainly to improve the facility for neutron capture therapy (NCT). In this facility, neutron beams with various energy spectra, from almost pure thermal to epithermal, are available. The evaluation of the neutron energy spectra by multi-activation-foil method was performed as a series of the facility characterization. The spectra at the normal irradiation position were evaluated for the combinations of heavy-water thickness of the spectrum shifter and the open-close condition of the cadmium and boral filters. The initial spectra were made mainly using a two-dimensional transport code, and the final spectra were obtained using an adjusting code. For the verification of the evaluated spectra, simulation calculations using a phantom were performed on the assumption of NCT-clinical-irradiation conditions. It resulted that the calculated data for the depth neutron-flux distributions were in good agreement with the experimental ones.

  15. 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.

  16. Gadolinium as a Neutron Capture Therapy Agent

    NASA Astrophysics Data System (ADS)

    Shih, Jing-Luen Allen

    The clinical results of treating brain tumors with boron neutron capture therapy are very encouraging and researchers around the world are once again making efforts to develop this therapeutic modality. Boron-10 is the agent receiving the most attention for neutron capture therapy but ^{157}Gd is a nuclide that also holds interesting properties of being a neutron capture therapy agent. The objective of this study is to evaluate ^{157}Gd as a neutron capture therapy agent. In this study it is determined that tumor concentrations of about 300 mug ^{157}Gd/g tumor can be achieved in brain tumors with some FDA approved MRI contrast agents such as Gd-DTPA and Gd-DOTA, and up to 628 mug ^{157 }Gd/g tumor can be established in bone tumors with Gd-EDTMP. Monte Carlo calculations show that with only 250 ppm of ^{157}Gd in tumor, neutron capture therapy can deliver 2,000 cGy to a tumor of 2 cm diameter or larger with 5 times 10^{12} n/cm ^2 fluence at the tumor. Dose measurements which were made with films and TLD's in phantoms verified these calculations. More extended Monte Carlo calculations demonstrate that neutron capture therapy with Gd possesses comparable dose distribution to B neutron capture therapy. With 5 times 10^{12 } n/cm^2 thermal neutrons at the tumor, Auger electrons from the Gd produced an optical density enhancement on the films that is similar to the effect caused by about 300 cGy of Gd prompt gamma dose which will further enhance the therapeutic effects. A technique that combines brachytherapy with Gd neutron capture therapy has been evaluated. Monte Carlo calculations show that 5,000 cGy of prompt gamma dose can be delivered to a treatment volume of 40 cm^3 with a 3-plane implant of a total of 9 Gd needles. The tumor to normal tissue advantage of this method is as good as ^{60} Co brachytherapy. Measurements of prompt gamma dose with films and TLD-700's in a lucite phantom verify the Monte Carlo evaluation. A technique which displays the Gd

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Recent advances in neutron capture therapy (NCT)

    SciTech Connect

    Fairchild, R.G.

    1985-01-01

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

  2. Spectromicroscopy in Boron Neutron Capture Therapy Research

    NASA Astrophysics Data System (ADS)

    Gilbert, Benjamin; Redondo, Jose; Andres, Roger; Suda, Takashi; Neumann, Michael; Steen, Steffi; Gabel, Detlef; Mercanti, Delio; Ciotti, Teresa; Perfetti, Paolo; Margaritondo, Giorgio; de Stasio, Gelsomina

    1998-03-01

    The MEPHISTO synchrotron imaging spectromicroscope can analyse ashed cells or tissue sections to reveal the microdistribution of trace elements. MEPHISTO performs core level x-ray absorption spectroscopy with synchrotron radiation, and uses an electron optics system to provide magnified photoelectron images. An application of the MEPHISTO spectromicroscope is in boron neutron capture therapy (BNCT). BNCT is a binary cancer therapy that will selectively destroy cancer cells provided that compounds containing a boron isotope are selectively accumulated in tumor tissue. Important factors for the success of BNCT include the ability to target every cancer cell, and the distribution of boron inside the cell. To investigate the boron distribution in tissue, sections of human glioblastoma containing a BNCT compound, and stained with nickel against a protein found in the nuclei of proliferating (cancer) cells, were studied with MEPHISTO.

  3. 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.

  4. 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.

  5. Neutron dosimetry in boron neutron capture therapy

    SciTech Connect

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

    1981-01-01

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

  6. Accelerator-driven boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Edgecock, Rob

    2014-05-01

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

  7. Boron neutron capture therapy: 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. PMID:27461603

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

    PubMed

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

    2016-01-01

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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Historic Methods for Capturing Magnetic Field Images

    ERIC Educational Resources Information Center

    Kwan, Alistair

    2016-01-01

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

  14. Historic Methods for Capturing Magnetic Field Images

    NASA Astrophysics Data System (ADS)

    Kwan, Alistair

    2016-03-01

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

  15. 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.

  16. 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.

  17. 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)

  18. Real-time dosimetry for boron-neutron capture therapy

    SciTech Connect

    Bliss, M.; Craig, R.A.; Reeder, P.L.; Sunberg, D.S.

    1994-09-01

    Epithermal/thermal boron neutron-capture therapy (BNCT) is promising treatment method for malignant tumors. Because the doses and dose rates for medical therapeutic radiation are very close to the normal tissue tolerance, small errors in radiation delivery can result in harmful overdoses. A substantial need exists for a device that will monitor, in real time, the radiation dose being delivered to a patient. Pacific Northwest Laboratory (PNL) has developed a scintillating glass optical fiber that is sensitive to thermal neutrons. The small size of the fibers offers the possibility of in vivo dose monitoring at several points within the radiation field. The count rate of such detectors can approach 10 MHz because the lifetime of the cerium activator is fast. Fluxes typical of those in BNCT (i.e., 10{sup 9} n/cm{sup 2}/sec) may be measured because of this potentially high count rate and the small diameter of the fiber.

  19. Multi-nuclear MRS and 19F MRI of 19F-labelled and 10B-enriched p-boronophenylalanine-fructose complex to optimize boron neutron capture therapy: phantom studies at high magnetic fields.

    PubMed

    Porcari, Paola; Capuani, Silvia; Campanella, Renzo; La Bella, Angela; Migneco, Luisa Maria; Maraviglia, Bruno

    2006-06-21

    Reaction yield optimization for the synthesis and the complexation of a boron neutron capture therapy agent (19)F-labelled, (10)B-enriched p-boronophenylalanine-fructose ((19)F-BPA-fr) complex was obtained. (1)H, (19)F, (13)C and (10)B magnetic resonance spectroscopy (MRS) of the (19)F-BPA-fr complex in aqueous and rat blood solution phantoms and its spatial distribution mapping using (19)F magnetic resonance imaging (MRI) results are reported. 7 T and 9.4 T magnetic fields were used to perform MRI and MRS respectively. Our in vitro results suggest that in vivo studies on (19)F-BPA through (19)F NMR will be feasible. PMID:16757868

  20. 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.

  1. 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.

  2. 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.

  3. 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.

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

    DOEpatents

    Miura, Michiko; Slatkin, Daniel N.

    1997-08-05

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

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

    DOEpatents

    Miura, 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.

  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. 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.}

  8. [Liposomal boron delivery system for neutron capture therapy].

    PubMed

    Nakamura, Hiroyuki

    2008-02-01

    Boron neutron capture therapy (BNCT) is a binary cancer treatment based on the nuclear reaction of two essentially nontoxic species, (10)B and thermal neutrons. 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 the liposomal boron delivery system (BDS) as a recent promising approach that meets 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. Various boronated liposomes have been developed and significant boron accumulation into tumor tissue with high tumor/blood boron ratios has been achieved by BDS.

  9. 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.

  10. Clinical considerations for neutron capture therapy of brain tumors

    SciTech Connect

    Madoc-Jones, H.; Wazer, D.E.; Zamenhof, R.G.; Harling, O.K.; Bernard, J.A. Jr. )

    1990-01-01

    The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the United States in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should now be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam causes gamma rays to be generated when it interacts with tissue, we think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue. I look forward to the remainder of this Workshop, which will detail recent progress in the development of epithermal, as well as thermal, beams and new methods for tracking and measuring the uptake of boron in normal and tumor tissues. 10 references.

  11. 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.

  12. Experience of boron neutron capture therapy in Japan

    NASA Astrophysics Data System (ADS)

    Kanda, Keiji

    1997-02-01

    In Japan the boron neutron capture therapy has been applied to more than 200 patients, mostly brain tumors and some melanomas. For brain tumors, Kyoto University, Kyoto Prefectural University of Medicine, Tsukuba University and National Kagawa Children's Hospital accept patients, and for melanomas, Kobe University and Mishima Institute of Dermatological Research accept patients so far. Recently the heavy water facility of Kyoto University Reactor has been upgraded for epithermal neutron as well as thermal neutron irradiations, and for the patient treatment during the continuous operation of the KUR.

  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. 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.

  15. Isodose Curves and Treatment Planning for Boron Neutron Capture Therapy.

    NASA Astrophysics Data System (ADS)

    Liu, Hungyuan B.

    The development of Boron Neutron Capture Therapy (BNCT) has been progressing in both ^{10 }B compound development and testing and neutron beam delivery. Animal tests are now in progress with several ^{10}B compounds and once the results of these animal tests are promising, patient trials can be initiated. The objective of this study is to create a treatment planning method based on the dose calculations by a Monte Carlo code of a mixed radiation field to provide linkage between phantom dosimetry and patient irradiation. The research started with an overall review of the development of BNCT. Three epithermal neutron facilities are described, including the operating Brookhaven Medical Research Reactor (BMRR) beam, the designed Missouri University Research Reactor (MURR) beam, and a designed accelerator based neutron source. The flux and dose distributions in a head model have been calculated for irradiation by these neutron beams. Different beam parameters were inter -compared for effectiveness. Dosimetric measurements in an elliptical lucite phantom and a cylindrical water phantom were made and compared to the MCNP calculations for irradiation by the BMRR beam. Repeated measurements were made and show consistent. To improve the statistical results calculated by MCNP, a neutron source plane was designed to start neutrons at the BMRR irradiation port. The source plane was used with the phantoms for dosimetric calculations. After being verified by different phantom dosimetry and in-air flux measurements at the irradiation port, the source plane was used to calculate the flux and dose distributions in the head model. A treatment planning program was created for use on a PC which uses the MCNP calculated results as input. This program calculates the thermal neutron flux and dose distributions of each component of radiation in the central coronal section of the head model for irradiation by a neutron beam. Different combinations of head orientations and irradiation

  16. Boronated antibodies and promazine derivatives for potential neutron capture therapy

    SciTech Connect

    Alam, F.; Soloway, A.H.; Barth, R.F.; Adams, D.M.; Mafune, N.

    1986-01-01

    The theoretical basis for boron neutron capture therapy (BNCT) derives from the irradiation of /sup 10/B with thermal neutrons, resulting in a fission reaction yielding /sup 7/Li and alpha particles. The fission products have short path lengths and high linear energy transfer (LET). Each component of this binary system, thermal neutrons and /sup 10/B, independently are nontumoricidal, but together they can be highly lethal. Success depends on localizing enough of the /sup 10/B (approx.20 ..mu..g/g of tumor) and delivering a requisite fluence of thermal neutrons (approx.10/sup 13/ n/cm/sup 9/) at the site of the tumor. This report describes the boronation of antibodies and the development of boron-containing promazine derivatives to selectively deliver /sup 10/B to tumor cells for BNCT.

  17. Accelerator based epithermal neutron source for neutron capture therapy

    SciTech Connect

    Brugger, R.; Kunze, J.

    1991-05-01

    Several investigators have suggested that a charged particle accelerator with light element reactions might be able to produce enough epithermal neutrons to be useful in Neutron Capture Therapy. The reaction choice so far has been the Li(p,n) reaction with protons up to 2.5 MeV. A moderator around the target would reduce the faster neutrons down to the epithermal energy region. The goals of the present research are: identify better reactions; improve the moderators; and find better combinations of 1 and 2. The target is to achieve, at the patient location, an epithermal neutron current of greater than 10{sup 9}n/cm{sup 2}sec, with a dose to tissue from the neutrons alone of less than 10{sup {minus}10} rads/n and a dose from the gamma rays in the beam of less than 10{sup {minus}10} rads/n.

  18. 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.

  19. 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

  20. 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.

  1. 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. PMID:27250576

  2. 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.

  3. Assessment of ideal neutron beams for neutron capture therapy.

    PubMed

    Storr, G J

    1992-09-01

    The discrete-ordinates transport computer code DORT has been used to develop a two-dimensional cylindrical phantom model for use as a tool to assess beam design and dose distributions for boron neutron capture therapy. The model uses an S8 approximation for angular fluxes and a P3 Legendre approximation for scattering cross sections. A one-dimensional discrete-ordinates model utilizing the computer code ANISN was used to validate the energy-group structure used in the two-dimensional calculations. In the two-dimensional model the effects of varying basic parameters such as aperture width, neutron source energy, and tissue composition have been studied. Identical results were obtained when comparing narrow beam calculations to fine-mesh higher-order Sn treatments (up to S32), and with P5 cross sections. It is shown that, when the correct assessment volume is used, narrow beams will give little or no advantage for therapy even with an optimum-energy ideal neutron beam.

  4. 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

  5. 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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

    Herrera, María S.; González, Sara J.; Minsky, Daniel M.; Kreiner, Andrés J.

    2010-08-01

    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.

  8. 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.

  9. High-Resolution Light Field Capture With Coded Aperture.

    PubMed

    Wang, Yu-Ping; Wang, Li-Chun; Kong, De-Hui; Yin, Bao-Cai

    2015-12-01

    Acquiring light field with larger angular resolution and higher spatial resolution in low cost is the goal of light field capture. Combining or modifying traditional optical cameras is a usual method for designing light field capture equipment, among which most models should deliberate trade-off between angular and spatial resolution, but augmenting coded aperture avoids this consideration by multiplexing information from different views. On the basis of coded aperture, this paper suggests an improved light field camera model that has double measurements and one mask. The two compressive measurements are respectively realized by a coded aperture and a random convolution CMOS imager, the latter is used as imaging sensor of the camera. The single mask design permits high light efficiency, which enables the sampling images to have high clarity. The double measurement design keeps more correlation information, which is conductive to enhancing the reconstructed light field. The higher clarity and more correlation of samplings mean higher quality of rebuilt light field, which also means higher resolution under condition of a lower PSNR requirement for rebuilt light field. Experimental results have verified advantage of the proposed design: compared with the representative mask-based light field camera models, the proposed model has the highest reconstruction quality and a higher light efficiency.

  10. 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

  11. 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.

  12. 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)

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

    PubMed

    Lam, Edmund Y

    2015-11-01

    Photography is a cornerstone of imaging. Ever since cameras became consumer products more than a century ago, we have witnessed great technological progress in optics and recording mediums, with digital sensors replacing photographic films in most instances. The latest revolution is computational photography, which seeks to make image reconstruction computation an integral part of the image formation process; in this way, there can be new capabilities or better performance in the overall imaging system. A leading effort in this area is called the plenoptic camera, which aims at capturing the light field of an object; proper reconstruction algorithms can then adjust the focus after the image capture. In this tutorial paper, we first illustrate the concept of plenoptic function and light field from the perspective of geometric optics. This is followed by a discussion on early attempts and recent advances in the construction of the plenoptic camera. We will then describe the imaging model and computational algorithms that can reconstruct images at different focus points, using mathematical tools from ray optics and Fourier optics. Last, but not least, we will consider the trade-off in spatial resolution and highlight some research work to increase the spatial resolution of the resulting images. PMID:26560916

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

    PubMed

    Lam, Edmund Y

    2015-11-01

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

  15. 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.

  16. New concepts for compact accelerator/target for Boron Neutron Capture Therapy

    SciTech Connect

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

    1996-12-31

    Two new target concepts, NIFTI and DISCOS, that enable a large reduction in the proton beam current needed to produce epithermal neutrons for BNCT (Boron Neutron Capture Therapy) are described. In the NIFTI concept, high energy neutrons produced by (p, n) reactions of 2.5 MeV protons on Li are down scattered to treatment energies ({approximately} 20 keV) by relatively thin layers of PbF{sub 2} and iron. In the DISCOS concept, treatment energy neutrons are produced directly in a succession of thin ({approximately} 1 micron) liquid Li films on rotating Be foils. These foils interact with a proton beam that operates just above threshold for the (p, n) reaction, with an applied DC field to re-accelerate the proton beam between the target foils.

  17. 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

  18. 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).

  19. The design, construction and performance of a variable collimator for epithermal neutron capture therapy beams.

    PubMed

    Riley, K J; Binns, P J; Ali, S J; Harling, O K

    2004-05-21

    A patient collimator for the fission converter based epithermal neutron beam (FCB) at the Massachusetts Institute of Technology Research Reactor (MITR-II) was built for clinical trials of boron neutron capture therapy (BNCT). A design was optimized by Monte Carlo simulations of the entire beam line and incorporates a modular construction for easy modifications in the future. The device was formed in-house by casting a mixture of lead spheres (7.6 mm diameter) in epoxy resin loaded with either 140 mg cm(-3) of boron carbide or 210 mg cm(-3) of lithium fluoride (95% enriched in 6Li). The cone shaped collimator allows easy field placement anywhere on the patient and is equipped with a laser indicator of central axis, beam's eye view optics and circular apertures of 80, 100, 120 and 160 mm diameter. Beam profiles and the collateral dose in a half-body phantom were measured for the 160 mm field using fission counters, activation foils as well as tissue equivalent (A-150) and graphite walled ionization chambers. Leakage radiation through the collimator contributes less than 10% to the total collateral dose up to 0.15 m beyond the edge of the aperture and becomes relatively more prominent with lateral displacement. The measured whole body dose equivalent of 24 +/- 2 mSv per Gy of therapeutic dose is comparable to doses received during conventional therapy and is due principally (60-80%) to thermal neutron capture reactions with boron. These findings, together with the dose distributions for the primary beam, demonstrate the suitability of this patient collimator for BNCT.

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

    PubMed Central

    Farhood, Bagher

    2014-01-01

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

  1. 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

  2. Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy.

    PubMed

    Xiong, Hejian; Wei, Xing; Zhou, Dongfang; Qi, Yanxin; Xie, Zhigang; Chen, Xuesi; Jing, Xiabin; Huang, Yubin

    2016-09-21

    Carboranes with rich boron content have showed significant applications in the field of boron neutron capture therapy. Biodegradable derivatives of carborane-conjugated polymers with well-defined structure and tunable loading of boron atoms are far less explored. Herein, a new family of amphiphilic carborane-conjugated polycarbonates was synthesized by ring-opening polymerization of a carborane-installed cyclic carbonate monomer. Catalyzed by TBD from a poly(ethylene glycol) macroinitiator, the polymerization proceeded to relatively high conversions (>65%), with low polydispersity in a certain range of molecular weight. The boron content was readily tuned by the feed ratio of the monomer and initiator. The resultant amphiphilic polycarbonates self-assembled in water into spherical nanoparticles of different sizes depending on the hydrophilic-to-hydrophobic ratio. It was demonstrated that larger nanoparticles (PN150) were more easily subjected to protein adsorption and captured by the liver, and smaller nanoparticles (PN50) were more likely to enter cancer cells and accumulate at the tumor site. PN50 with thermal neutron irradiation exhibited the highest therapeutic efficacy in vivo. The new synthetic method utilizing amphiphilic biodegradable boron-enriched polymers is useful for developing more-selective and -effective boron delivery systems for BNCT. PMID:27548011

  3. Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy.

    PubMed

    Xiong, Hejian; Wei, Xing; Zhou, Dongfang; Qi, Yanxin; Xie, Zhigang; Chen, Xuesi; Jing, Xiabin; Huang, Yubin

    2016-09-21

    Carboranes with rich boron content have showed significant applications in the field of boron neutron capture therapy. Biodegradable derivatives of carborane-conjugated polymers with well-defined structure and tunable loading of boron atoms are far less explored. Herein, a new family of amphiphilic carborane-conjugated polycarbonates was synthesized by ring-opening polymerization of a carborane-installed cyclic carbonate monomer. Catalyzed by TBD from a poly(ethylene glycol) macroinitiator, the polymerization proceeded to relatively high conversions (>65%), with low polydispersity in a certain range of molecular weight. The boron content was readily tuned by the feed ratio of the monomer and initiator. The resultant amphiphilic polycarbonates self-assembled in water into spherical nanoparticles of different sizes depending on the hydrophilic-to-hydrophobic ratio. It was demonstrated that larger nanoparticles (PN150) were more easily subjected to protein adsorption and captured by the liver, and smaller nanoparticles (PN50) were more likely to enter cancer cells and accumulate at the tumor site. PN50 with thermal neutron irradiation exhibited the highest therapeutic efficacy in vivo. The new synthetic method utilizing amphiphilic biodegradable boron-enriched polymers is useful for developing more-selective and -effective boron delivery systems for BNCT.

  4. 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.

  5. 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.

  6. Proton-Proton Weak Capture in Chiral Effective Field Theory

    SciTech Connect

    Marcucci, Laura Elisa; Schiavilla, Rocco; Viviani, MIchele

    2013-05-01

    The astrophysical $S$-factor for proton-proton weak capture is calculated in chiral effective field theory over the center-of-mass relative-energy range 0--100 keV. The chiral two-nucleon potential derived up to next-to-next-to-next-to leading order is augmented by the full electromagnetic interaction including, beyond Coulomb, two-photon and vacuum-polarization corrections. The low-energy constants (LEC's) entering the weak current operators are fixed so as to reproduce the $A=3$ binding energies and magnetic moments, and the Gamow-Teller matrix element in tritium $\\beta$ decay. Contributions from $S$ and $P$ partial waves in the incoming two-proton channel are retained. The $S$-factor at zero energy is found to be $S(0)=(4.030 \\pm 0.006)\\times 10^{-23}$ MeV fm$^2$, with a $P$-wave contribution of $0.020\\times 10^{-23}$ MeV fm$^2$. The theoretical uncertainty is due to the fitting procedure of the LEC's and to the cutoff dependence. It is shown that polynomial fits to parametrize the energy dependence of the $S$-factor are inherently unstable.

  7. Proton-proton weak capture in chiral effective field theory.

    PubMed

    Marcucci, L E; Schiavilla, R; Viviani, M

    2013-05-10

    The astrophysical S factor for proton-proton weak capture is calculated in chiral effective field theory over the center-of-mass relative-energy range 0-100 keV. The chiral two-nucleon potential derived up to next-to-next-to-next-to leading order is augmented by the full electromagnetic interaction including, beyond Coulomb, two-photon and vacuum-polarization corrections. The low-energy constants entering the weak current operators are fixed so as to reproduce the A=3 binding energies and magnetic moments and the Gamow-Teller matrix element in tritium β decay. Contributions from S and P partial waves in the incoming two-proton channel are retained. The S factor at zero energy is found to be S(0)=(4.030±0.006)×10(-23) MeV fm(2), with a P-wave contribution of 0.020×10(-23) MeV fm(2). The theoretical uncertainty is due to the fitting procedure of the low-energy constants and to the cutoff dependence.

  8. Proton-proton weak capture in chiral effective field theory.

    PubMed

    Marcucci, L E; Schiavilla, R; Viviani, M

    2013-05-10

    The astrophysical S factor for proton-proton weak capture is calculated in chiral effective field theory over the center-of-mass relative-energy range 0-100 keV. The chiral two-nucleon potential derived up to next-to-next-to-next-to leading order is augmented by the full electromagnetic interaction including, beyond Coulomb, two-photon and vacuum-polarization corrections. The low-energy constants entering the weak current operators are fixed so as to reproduce the A=3 binding energies and magnetic moments and the Gamow-Teller matrix element in tritium β decay. Contributions from S and P partial waves in the incoming two-proton channel are retained. The S factor at zero energy is found to be S(0)=(4.030±0.006)×10(-23) MeV fm(2), with a P-wave contribution of 0.020×10(-23) MeV fm(2). The theoretical uncertainty is due to the fitting procedure of the low-energy constants and to the cutoff dependence. PMID:23705703

  9. Magnetic field therapy: a review.

    PubMed

    Markov, Marko S

    2007-01-01

    There is increasing interest in using permanent magnets for therapeutic purposes encouraged by basic science publications and clinical reports. Magnetotherapy provides a non invasive, safe, and easy method to directly treat the site of injury, the source of pain and inflammation, and other types of disease. The physiological bases for the use of magnetic fields for tissue repair as well as physical principles of dosimetry and application of various magnetic fields are subjects of this review. Analysis of the magnetic and electromagnetic stimulation is followed by a discussion of the advantage of magnetic field stimulation compared with electric current and electric field stimulation. PMID:17454079

  10. 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.

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

    PubMed

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

    2014-10-21

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

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

    SciTech Connect

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

    1999-06-06

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

  13. Mass spectral investigations of boron neutron capture therapy (BNCT) agents

    SciTech Connect

    Miller, D.L.; Peterson-Wright, L.J.

    1988-01-01

    We examined the use of mass spectrometry incorporating fast atom bombardment ionization to determine if the potential existed for the development of a HPLC FAB/MS analytical procedure utilizing the new continuous-flow FAB inlet. All experiments were conducted on a KRATOS MS890 equipped with an 8 kV MS50-type FAB source. The MS890 was equipped with an Ion Tech (11NF) saddle field ion gun and xenon was used as the FAB gas. Initial experiments using BSH were conducted in both positive and negative ion modes using a variety of FAB matrices. Positive ion experiments were discontinued when no peaks indicative of the compound of interest were observed. The positive ion spectra were dominated by peaks arising from sodium reacting with the various matrices used. Experiments conducted in the negative ion mode proved to be much more productive. A variety of matrices were tested with BSH. These matrices included glycerol, thioglycerol, 3-nitrobenzyl alcohol, triethanolamine, and PEG-600. No peaks indicative of the BSH compound were observed when glycerol was used as the matrix, even though the BSH was readily soluble. For the remainder of the matrices tested, good solubility of the BSH was also observed, as well as peaks using BSH containing the natural isotopic abundance of boron (approximately 20% /sup 10/B and 80% /sup 11/B). When examined using thioglycerol as the matrix, a cluster of peaks indicative of boron was observed with the most intense peak occurring at M/Z 197.

  14. 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

  15. 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

  16. MAGNETIC FIELD-DECAY-INDUCED ELECTRON CAPTURES: A STRONG HEAT SOURCE IN MAGNETAR CRUSTS

    SciTech Connect

    Cooper, Randall L.; Kaplan, David L. E-mail: dkaplan@kitp.ucsb.edu

    2010-01-10

    We propose a new heating mechanism in magnetar crusts. Magnetars' crustal magnetic fields are much stronger than their surface fields; therefore, magnetic pressure partially supports the crust against gravity. The crust loses magnetic pressure support as the field decays and must compensate by increasing the electron degeneracy pressure; the accompanying increase in the electron Fermi energy induces nonequilibrium, exothermic electron captures. The total heat released via field-decay electron captures is comparable to the total magnetic energy in the crust. Thus, field-decay electron captures are an important, if not the primary, mechanism powering magnetars' soft X-ray emission.

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

    SciTech Connect

    Mitchell, H.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 10{sup 7} 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/AlF{sub 3} composite and a stacked Al/Teflon design) at various incident electron energies.

  18. A state-of-the-art epithermal neutron irradiation facility for neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Riley, K. J.; Binns, P. J.; Harling, O. K.

    2004-08-01

    At the Massachusetts Institute of Technology (MIT) the first fission converter-based epithermal neutron beam (FCB) has proven suitable for use in clinical trials of boron neutron capture therapy (BNCT). The modern facility provides a high intensity beam together with low levels of contamination that is ideally suited for use with future, more selective boron delivery agents. Prescriptions for normal tissue tolerance doses consist of 2 or 3 fields lasting less than 10 min each with the currently available beam intensity, that are administered with an automated beam monitoring and control system to help ensure safety of the patient and staff alike. A quality assurance program ensures proper functioning of all instrumentation and safety interlocks as well as constancy of beam output relative to routine calibrations. Beam line shutters and the medical room walls provide sufficient shielding to enable access and use of the facility without affecting other experiments or normal operation of the multipurpose research reactor at MIT. Medical expertise and a large population in the greater Boston area are situated conveniently close to the university, which operates the research reactor 24 h a day for approximately 300 days per year. The operational characteristics of the facility closely match those established for conventional radiotherapy, which together with a near optimum beam performance ensure that the FCB is capable of determining whether the radiobiological promise of NCT can be realized in routine practice.

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

    NASA Astrophysics Data System (ADS)

    Sakurai, Yoshinori; Ono, Koji

    2007-12-01

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

  20. A state-of-the-art epithermal neutron irradiation facility for neutron capture therapy.

    PubMed

    Riley, K J; Binns, P J; Harling, O K

    2004-08-21

    At the Massachusetts Institute of Technology (MIT) the first fission converter-based epithermal neutron beam (FCB) has proven suitable for use in clinical trials of boron neutron capture therapy (BNCT). The modern facility provides a high intensity beam together with low levels of contamination that is ideally suited for use with future, more selective boron delivery agents. Prescriptions for normal tissue tolerance doses consist of 2 or 3 fields lasting less than 10 min each with the currently available beam intensity, that are administered with an automated beam monitoring and control system to help ensure safety of the patient and staff alike. A quality assurance program ensures proper functioning of all instrumentation and safety interlocks as well as constancy of beam output relative to routine calibrations. Beam line shutters and the medical room walls provide sufficient shielding to enable access and use of the facility without affecting other experiments or normal operation of the multipurpose research reactor at MIT. Medical expertise and a large population in the greater Boston area are situated conveniently close to the university, which operates the research reactor 24 h a day for approximately 300 days per year. The operational characteristics of the facility closely match those established for conventional radiotherapy, which together with a near optimum beam performance ensure that the FCB is capable of determining whether the radiobiological promise of NCT can be realized in routine practice.

  1. Expanding use of pulsed electromagnetic field therapies.

    PubMed

    Markov, Marko S

    2007-01-01

    Various types of magnetic and electromagnetic fields are now in successful use in modern medicine. Electromagnetic therapy carries the promise to heal numerous health problems, even where conventional medicine has failed. Today, magnetotherapy provides a non invasive, safe, and easy method to directly treat the site of injury, the source of pain and inflammation, and a variety of diseases and pathologies. Millions of people worldwide have received help in treatment of the musculoskeletal system, as well as for pain relief. Pulsed electromagnetic fields are one important modality in magnetotherapy. Recent technological innovations, implementing advancements in computer technologies, offer excellent state-of-the-art therapy. PMID:17886012

  2. 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.

  3. Case numbers for a randomized clinical trial of boron neutron capture therapy for Glioblastoma multiforme.

    PubMed

    Sander, Anja; Wosniok, Werner; Gabel, Detlef

    2014-06-01

    Boron neutron capture therapy (BNCT) with Na2B12H11SH (BSH) or p-dihydroxyborylphenylalanine (BPA), and with a combination of both, was compared to radiotherapy with temozolomide, and the number of patients required to show statistically significant differences between the treatments was calculated. Whereas arms using BPA require excessive number of patients in each arm, a two-armed clinical trial with BSH and radiotherapy plus temozolomide is feasible. PMID:24373823

  4. 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.

  5. 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.

  6. Neutron capture autoradiographic determination of 10B distributions and concentrations in biological samples for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Yanagie, Hironobu; Ogura, Koichi; Matsumoto, Toshio; Eriguchi, Masazumi; Kobayashi, Hisao

    1999-11-01

    It is necessary for effective boron neutron capture therapy (BNCT) to accumulate 10B atoms in the tumor cells. We prepared a cationic liposome entrapped 10B compound for the delivery system and examined the delivery capacity of 10B atoms to pancreatic cancer cell, AsPC-1, in vivo. It is required to achieve an accurate measurement of 10B distributions and concentrations in biological samples with a sensitivity in the ppm range for BNCT. We applied CR-39 (polyallyldiglycol carbonate) plastic track detectors to α-autoradiographic measurements of the 10B biodistribution in sliced whole-body samples of mice. To selectively desensitize undesirable proton tracks, we applied PEW (KOH+C 2H 5OH+H 2O) solution to the etching of CR-39 detector. The subsequent use of an alpha-track radiographic image analysis system enabled a discrimination between alpha tracks and recoiled proton tracks by the track size selection method. This enabled us to estimate quantitatively the distributions of 10B concentrations within the tissue sections by comparing with suitable standards.

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  8. Field testing the wildlink capture collar on wolves

    USGS Publications Warehouse

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

    1992-01-01

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

  9. 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

  10. 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.

  11. 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.

  12. {sup 33}S for Neutron Capture Therapy: Nuclear Data for Monte Carlo Calculations

    SciTech Connect

    Porras, I.; Sabaté-Gilarte, M.; Praena, J.; Quesada, J.M.; Esquinas, P.L.

    2014-06-15

    A study of the nuclear data required for the Monte Carlo simulation of boron neutron capture therapy including the {sup 33}S isotope as an enhancer of the dose at small depths has been performed. In particular, the controversy on the available data for the {sup 33}S(n, α) cross section will be shown, which motivates new measurements. In addition to this, kerma factors for the main components of tissue are calculated with the use of fitting functions. Finally, we have applied these data to a potential neutron capture treatment with boron and sulfur addition to tissue in which part of the hydrogen atoms are replaced by deuterium, which improves the procedure.

  13. LaBr3(Ce) gamma-ray detector for neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Smirnova, M.; Shmanin, E.; Galavanov, A.; Shustov, A.; Ulin, S.; Vlasik, K.; Dmitrenko, V.; Novikov, A.; Orlov, A.; Petrenko, D.; Shmurak, S.; Uteshev, Z.

    2016-02-01

    Results of developing of a gamma-ray detector based on LaBr3(Ce) scintillation crystal for neutron capture therapy are presented. An energy resolution of the detector measured by photomultiplier tube Hamamatsu R6233-100 is showed. It was 2.93% for gamma line 662 keV from a source 137Cs. For radiative capture gamma line of isotope 10B (478 keV) and annihilation line (511 keV) the values were 3.33 and 3.24% respectively. Data analysis of gamma spectra for an estimation of energy resolution threshold required for visual identification gamma lines 478 and 511 keV was made.

  14. Thought field therapy and trauma recovery.

    PubMed

    Folkes, Crystal E

    2002-01-01

    People who have been repeatedly exposed to traumatic events are at high risk for Post Traumatic Stress Disorder (PTSD). Refugees and immigrants can certainly be in this category, but seldom seek professional therapy due to cultural, linguistic, financial, and historical reasons. A rapid and culturally sensitive treatment is highly desirable with communities new to Western-style healing. In this study of 31 clients, a pre-test was given, all participants received Thought Field Therapy (TFT), and were then post-tested after 30 days. Pre-test and post-test total scores showed a significant drop in all symptom sub-groupings of the DSM criteria for PTSD. The findings of this study contrast with the outcomes of other methods of treatment, and are a significant addition to the growing body of data on refugee mental health. PMID:12166020

  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. Boron neutron capture therapy for glioblastoma: improvement of boron biodistribution by hyaluronidase.

    PubMed

    Haselsberger, K; Radner, H; Pendl, G

    1998-09-11

    Boron neutron capture therapy (BNCT) represents a highly promising therapeutic alternative for the treatment of the most common malignant brain tumor, glioblastoma multiforme. Both the efficacy and safety of BNCT are greatly dependent on the pattern of 10B biodistribution. The present study investigates the influence of systemic hyaluronidase applied in combination with Na2B12H11SH (BSH), a boron carrier used in current clinical trials. The application of hyaluronidase was associated with a statistically significant improvement in the tumor/blood boron concentration ratio which suggests that hyaluronidase is capable of enhancing the therapeutic potential of BSH.

  17. 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. PMID:24447933

  18. 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.

  19. Feasibility study on pinhole camera system for online dosimetry in boron neutron capture therapy.

    PubMed

    Katabuchi, Tatsuya; Hales, Brian; Hayashizaki, Noriyosu; Igashira, Masayuki; Khan, Zareen; Kobayashi, Tooru; Matsuhashi, Taihei; Miyazaki, Koichi; Ogawa, Koichi; Terada, Kazushi

    2014-06-01

    The feasibility of a pinhole camera system for online dosimetry in boron neutron capture therapy (BNCT) was studied. A prototype system was designed and built. Prompt γ-rays from the (10)B(n,α)(7)Li reaction from a phantom irradiated with neutrons were detected with the prototype system. An image was reconstructed from the experimental data. The reconstructed image showed a good separation of the two borated regions in the phantom. The counting rates and signal-to-noise ratio when using the system in actual BNCT applications are also discussed.

  20. 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.

  1. 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).

  2. 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.

  3. Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors.

    PubMed

    Zamenhof, R G; Clement, S D; Harling, O K; Brenner, J F; Wazer, D E; Madoc-Jones, H; Yanch, J C

    1990-01-01

    Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces (with RBE weighting) a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction. With parallel-opposed lateral irradiation, the planar advantage depth contour for this beam

  4. Static magnetic field therapy: dosimetry considerations.

    PubMed

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

    2008-06-01

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

  5. 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.

  6. 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.

  7. 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.

  8. a New Method for Neutron Capture Therapy (nct) and Related Simulation by MCNP4C Code

    NASA Astrophysics Data System (ADS)

    Shirazi, Mousavi; Alireza, Seyed; Ali, Taheri

    2010-01-01

    Neutron capture therapy (NCT) is enumerated as one of the most important methods for treatment of some strong maladies among cancers in medical science thus is unavoidable controlling and protecting instances in use of this science. Among of treatment instances of this maladies with use of nuclear medical science is use of neutron therapy that is one of the most important and effective methods in treatment of cancers. But whereas fast neutrons have too destroyer effects and also sake of protection against additional absorbed energy (absorbed dose) by tissue during neutron therapy and also naught damaging to rest of healthy tissues, should be measured absorbed energy by tissue accurately, because destroyer effects of fast neutrons is almost quintuple more than gamma photons. In this article for neutron therapy act of male's liver has been simulated a system by the Monte Carlo method (MCNP4C code) and also with use of analytical method, thus absorbed dose by this tissue has been obtained for sources with different energies accurately and has been compared results of this two methods together.

  9. Self-shielding effects in neutron spectra measurements for neutron capture therapy by means of activation foils.

    PubMed

    Pytel, Krzysztof; Józefowicz, Krystyna; Pytel, Beatrycze; Koziel, Alina

    2004-01-01

    The design and optimisation of a neutron beam for neutron capture therapy (NCT) is accompanied by the neutron spectra measurements at the target position. The method of activation detectors was applied for the neutron spectra measurements. Epithermal neutron energy region imposes the resonance structure of activation cross sections resulting in strong self-shielding effects. The neutron self-shielding correction factor was calculated using a simple analytical model of a single absorption event. Such a procedure has been applied to individual cross sections from pointwise ENDF/B-VI library and new corrected activation cross sections were introduced to a spectra unfolding algorithm. The method has been verified experimentally both for isotropic and for parallel neutron beams. Two sets of diluted and non-diluted activation foils covered with cadmium were irradiated in the neutron field. The comparison of activation rates of diluted and non-diluted foils has demonstrated the correctness of the applied self-shielding model.

  10. Microscale magnetic field modulation for enhanced capture and distribution of rare circulating tumor cells.

    PubMed

    Chen, Peng; Huang, Yu-Yen; Hoshino, Kazunori; Zhang, John X J

    2015-03-04

    Immunomagnetic assay combines the powers of the magnetic separation and biomarker recognition and has been an effective tool to perform rare Circulating Tumor Cells detection. Key factors associated with immunomagnetic assay include the capture rate, which indicates the sensitivity of the system, and distributions of target cells after capture, which impact the cell integrity and other biological properties that are critical to downstream analyses. Here we present a theoretical framework and technical approach to implement a microscale magnetic immunoassay through modulating local magnetic field towards enhanced capture and distribution of rare cancer cells. Through the design of a two-dimensional micromagnet array, we characterize the magnetic field generation and quantify the impact of the micromagnets on rare cell separation. Good agreement is achieved between the theory and experiments using a human colon cancer cell line (COLO205) as the capture targets.

  11. Homogeneous immunoconjugates for boron neutron-capture therapy: design, synthesis, and preliminary characterization.

    PubMed

    Guan, L; Wims, L A; Kane, R R; Smuckler, M B; Morrison, S L; Hawthorne, M F

    1998-10-27

    The application of immunoprotein-based targeting strategies to the boron neutron-capture therapy of cancer poses an exceptional challenge, because viable boron neutron-capture therapy by this method will require the efficient delivery of 10(3) boron-10 atoms by each antigen-binding protein. Our recent investigations in this area have been focused on the development of efficient methods for the assembly of homogeneous immunoprotein conjugates containing the requisite boron load. In this regard, engineered immunoproteins fitted with unique, exposed cysteine residues provide attractive vehicles for site-specific modification. Additionally, homogeneous oligomeric boron-rich phosphodiesters (oligophosphates) have been identified as promising conjugation reagents. The coupling of two such boron-rich oligophosphates to sulfhydryls introduced to the CH2 domain of a chimeric IgG3 has been demonstrated. The resulting boron-rich immunoconjugates are formed efficiently, are readily purified, and have promising in vitro and in vivo characteristics. Encouragingly, these studies showed subtle differences in the properties of the conjugates derived from the two oligophosphate molecules studied, providing a basis for the application of rational design to future work. Such subtle details would not have been as readily discernible in heterogeneous conjugates, thus validating the rigorous experimental design employed here.

  12. Homogeneous immunoconjugates for boron neutron-capture therapy: Design, synthesis, and preliminary characterization

    PubMed Central

    Guan, Lufeng; Wims, Letitia A.; Kane, Robert R.; Smuckler, Mark B.; Morrison, Sherie L.; Hawthorne, M. Frederick

    1998-01-01

    The application of immunoprotein-based targeting strategies to the boron neutron-capture therapy of cancer poses an exceptional challenge, because viable boron neutron-capture therapy by this method will require the efficient delivery of 103 boron-10 atoms by each antigen-binding protein. Our recent investigations in this area have been focused on the development of efficient methods for the assembly of homogeneous immunoprotein conjugates containing the requisite boron load. In this regard, engineered immunoproteins fitted with unique, exposed cysteine residues provide attractive vehicles for site-specific modification. Additionally, homogeneous oligomeric boron-rich phosphodiesters (oligophosphates) have been identified as promising conjugation reagents. The coupling of two such boron-rich oligophosphates to sulfhydryls introduced to the CH2 domain of a chimeric IgG3 has been demonstrated. The resulting boron-rich immunoconjugates are formed efficiently, are readily purified, and have promising in vitro and in vivo characteristics. Encouragingly, these studies showed subtle differences in the properties of the conjugates derived from the two oligophosphate molecules studied, providing a basis for the application of rational design to future work. Such subtle details would not have been as readily discernible in heterogeneous conjugates, thus validating the rigorous experimental design employed here. PMID:9789066

  13. 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

  14. Plasma injection and capture at electron cyclotron resonance in a mirror system with additional rf fields

    SciTech Connect

    Golovanivskii, K.S.; Dugar-Zhabon, V.D.; Karyaka, V.I.; Milant'ev, V.P.; Turikov, V.A.

    1980-03-01

    Experiments and numerical simulations have been carried out to determine how cyclotron-resonance rf fields in an open magnetic mirror system affect the capture and confinement of a plasma injected along the axis. The results show that at electron cyclotron resonance the fields greatly improve the longitudinal plasma confinement.

  15. Capture of a high density field reversed configuration in a flux conserver

    NASA Astrophysics Data System (ADS)

    Sieck, P. E.; Intrator, T. P.; Wurden, G. A.; Sun, X.; Cortez, R. J.; Waganaar, W. J.

    2008-11-01

    A physics demonstration of Magnetized Target Fusion (MTF) is being pursued by a collaborative team from Los Alamos National Laboratory and Air Force Research Laboratory. The approach is to form a high density Field Reversed Configuration (FRC), translate it into a liner, and adiabatically compress the FRC by imploding the liner. Capture of the FRC in the liner is critical to the success of the experiment. Several interesting phenomena are possible. The FRC can undergo heating when it bounces off the end mirror. Also, partial capture of the FRC can occur such that a smaller FRC remains captured while some plasma and magnetic energy ejects from the liner. Magnetic mirrors at both the upstream and downstream ends of the capture section help to determine the prominence of these behaviors. The translation and capture regions of the experiment are instrumented with flux loops and surface magnetic field diagnostics. Plans will be presented for internal magnetic field probes in these regions. Implications for optimum capture geometry for compression experiments will be discussed. This work is supported by the Office of Fusion Energy Sciences, and DOE/LANL contract DE-AC52-06NA25396.

  16. Fission reactor neutron sources for neutron capture therapy--a critical review.

    PubMed

    Harling, Otto K; Riley, Kent J

    2003-01-01

    The status of fission reactor-based neutron beams for neutron capture therapy (NCT) is reviewed critically. Epithermal neutron beams, which are favored for treatment of deep-seated tumors, have been constructed or are under construction at a number of reactors worldwide. Some of the most recently constructed epithermal neutron beams approach the theoretical optimum for beam purity. Of these higher quality beams, at least one is suitable for use in high through-put routine therapy. It is concluded that reactor-based epithermal neutron beams with near optimum characteristics are currently available and more can be constructed at existing reactors. Suitable reactors include relatively low power reactors using the core directly as a source of neutrons or a fission converter if core neutrons are difficult to access. Thermal neutron beams for NCT studies with small animals or for shallow tumor treatments, with near optimum properties have been available at reactors for many years. Additional high quality thermal beams can also be constructed at existing reactors or at new, small reactors. Furthermore, it should be possible to design and construct new low power reactors specifically for NCT, which meet all requirements for routine therapy and which are based on proven and highly safe reactor technology.

  17. Iodine neutron capture therapy: A new generation of radiotherapy for the thyroid

    SciTech Connect

    Ahmed, K.F.; Stephens, A.G.; Spall, R.D.; Brey, R.R.; Bennion, J.S.

    1997-12-01

    An innovative technique is being pursued that takes advantage of noninvasive, in situ neutron capture therapy concepts for treating hyperthyroidism and thyroid carcinoma. Present treatment techniques include surgical removal of the thyroid or, more frequently, the oral administration of {sup 131}I. Therapeutic applications of {sup 131}I are complicated by the unavoidable and undesirable exposure of ancillary body organs, protracted treatment times due to long effective half-life, and less than ideal radiation emission characteristics, i.e., low-effective energy available for deposition in the target organ. These problems are mitigated through the use of {sup 128}I. Table I provides pertinent radiological characteristics for a comparison of {sup 131}I with {sup 128}I.

  18. 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.

  19. Using the TREAT reactor in support of boron neutron capture therapy (BNCT) experiments: A feasibility analysis

    SciTech Connect

    Grasseschi, G.L.; Schaefer, R.W.

    1996-03-01

    The technical feasibility of using the TREAT reactor facility for boron neutron capture therapy (BNCT) research was assessed. Using one-dimensional neutronics calculations, it was shown that the TREAT core neutron spectrum can be filtered to reduce the undesired radiation (contamination) dose per desired neutron more effectively than can the core spectra from two prominent candidate reactors. Using two-dimensional calculations, it was demonstrated that a non-optimized filter replacing the TREAT thermal column can yield a fluence of desired-energy neutrons more than twice as large as the fluence believed to be required and, at the same time, have a contamination dose per desired neutron almost as low as that from any other candidate facility. The time, effort and cost required to adapt TREAT for a mission supporting BNCT research would be modest.

  20. Effect of boron neutron capture therapy for recurrent anaplastic meningioma: an autopsy case report.

    PubMed

    Kawaji, Hiroshi; Miyatake, Shin-Ichi; Shinmura, Kazuya; Kawabata, Shinji; Tokuyama, Tsutomu; Namba, Hiroki

    2015-01-01

    A 70-year-old woman died of systemic metastasis from anaplastic meningioma and underwent autopsy. The patient underwent twice total removal of the right sphenoid ridge meningioma 2 years ago. The tumor recurred 3 times, and then stereotactic radiotherapy was employed. Boron neutron capture therapy (BNCT) was performed for the fourth local recurrence and an additional new lesion. Proliferative activity of the newly developed meningioma, which had been treated with BNCT only, was significantly lower than that of untreated metastatic liver tumor, as well as that of the meningioma specimen obtained at the second surgery. Our pathological findings demonstrated, for the first time, the therapeutic effect of BNCT on anaplastic meningioma at an early stage (2.5 months).

  1. 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.

  2. 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)

  3. 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.

  4. 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.

  5. Accelerator based epithermal neutron source for neutron capture therapy. Annual report, [October 1990--April 1991

    SciTech Connect

    Brugger, R.; Kunze, J.

    1991-05-01

    Several investigators have suggested that a charged particle accelerator with light element reactions might be able to produce enough epithermal neutrons to be useful in Neutron Capture Therapy. The reaction choice so far has been the Li(p,n) reaction with protons up to 2.5 MeV. A moderator around the target would reduce the faster neutrons down to the epithermal energy region. The goals of the present research are: identify better reactions; improve the moderators; and find better combinations of 1 and 2. The target is to achieve, at the patient location, an epithermal neutron current of greater than 10{sup 9}n/cm{sup 2}sec, with a dose to tissue from the neutrons alone of less than 10{sup {minus}10} rads/n and a dose from the gamma rays in the beam of less than 10{sup {minus}10} rads/n.

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

    PubMed Central

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

    2006-01-01

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

  7. Neutron-induced gamma dose from a reactor beam filter for boron neutron capture therapy.

    PubMed

    Harrington, B V

    1989-01-01

    For the boron neutron capture therapy (NCT) of deep-seated metastatic melanoma, an epithermal (up to a few keV energy) neutron beam from a reactor horizontal facility could be useful if the inherent contamination from fast neutrons and gamma rays could be minimised. Calculations for ANSTO's 10 MW research reactor HIFAR have shown that, even though a filter material such as AlF3 attenuates the fast neutron dose, the beam quality improvement is counteracted by a relative increase in the gamma dose because of the gammas arising from neutron captures in the filter material, particularly the aluminium. The aluminium gammas, most of which arise from thermal neutron capture, are hard and cannot be attenuated by lead or bismuth without comparable attenuation of the epithermal neutron flux. Addition of an absorber such as 6Li to the AlF3 filter was investigated as a means of reducing the hard gamma dose, but the improvement in beam quality was small and at considerable cost to dose intensity. Dose characteristics calculations confirmed the superiority of a tangential beam over a radial beam with better results from an unfiltered tangential beam than from an AlF3 filter in a radial beam. This study showed conclusively that assessments of filter assemblies based on the effect of individual components on either the neutron or gamma dose in isolation are inadequate. In assessing any epithermal neutron filter, thermal neutron shield, and gamma shield combination, the total effect of each on the neutron, gamma, and boron-10 dose must be considered.

  8. Engineering tumor-targeted gadolinium hexanedione nanoparticles for potential application in neutron capture therapy.

    PubMed

    Oyewumi, Moses O; Mumper, Russell J

    2002-01-01

    Microemulsions (oil-in-water) have been employed as templates to engineer nanoparticles containing high concentrations of gadolinium for potential application in neutron capture therapy of tumors. Gadolinium hexanedione (GdH), synthesized by complexation of Gd(3+) with 2,4-hexanedione, was used as the nanoparticle matrix alone or in combination with either emulsifying wax or PEG-400 monostearate. Solid nanoparticles (<125 nm size) were obtained by simple cooling of the microemulsions prepared at 60 degrees C to room temperature in one vessel. The feasibility of tumor targeting via folate receptors was studied. A folate ligand was synthesized by chemically linking folic acid to distearoylphosphatidylethanolamine (DSPE) via a poly(ethylene glycol) (PEG; MW 3350) spacer. To obtain folate-coated nanoparticles, the folate ligand (0.75% w/w to 15% w/w) was added to either the microemulsion templates at 60 degrees C or nanoparticle suspensions at 25 degrees C. Efficiencies of folate ligand attachment/adsorption to nanoparticle formulations were monitored by gel permeation chromatography. Cell uptake studies were carried out in KB cells (human nasopharyngeal epidermal carcinoma cell line), known to overexpress folate receptors. The uptake of folate-coated nanoparticles was about 10-fold higher than uncoated nanoparticles after 30 min at 37 degrees C. The uptake of folate-coated nanoparticles at 4 degrees C was 20-fold lower than the uptake at 37 degrees C and comparable to the uptake of uncoated nanoparticles at 37 degrees C. Folate-mediated endocytosis was further verified by the inhibition of folate-coated nanoparticles uptake by free folic acid. It was observed that folate-coated nanoparticles uptake decreased to approximately 2% of its initial value with the coincubation of 0.001 mM of free folic acid. The results suggested that these tumor-targeted nanoparticles containing high concentrations of Gd may have potential for neutron capture therapy. PMID:12440870

  9. Engineering tumor-targeted gadolinium hexanedione nanoparticles for potential application in neutron capture therapy.

    PubMed

    Oyewumi, Moses O; Mumper, Russell J

    2002-01-01

    Microemulsions (oil-in-water) have been employed as templates to engineer nanoparticles containing high concentrations of gadolinium for potential application in neutron capture therapy of tumors. Gadolinium hexanedione (GdH), synthesized by complexation of Gd(3+) with 2,4-hexanedione, was used as the nanoparticle matrix alone or in combination with either emulsifying wax or PEG-400 monostearate. Solid nanoparticles (<125 nm size) were obtained by simple cooling of the microemulsions prepared at 60 degrees C to room temperature in one vessel. The feasibility of tumor targeting via folate receptors was studied. A folate ligand was synthesized by chemically linking folic acid to distearoylphosphatidylethanolamine (DSPE) via a poly(ethylene glycol) (PEG; MW 3350) spacer. To obtain folate-coated nanoparticles, the folate ligand (0.75% w/w to 15% w/w) was added to either the microemulsion templates at 60 degrees C or nanoparticle suspensions at 25 degrees C. Efficiencies of folate ligand attachment/adsorption to nanoparticle formulations were monitored by gel permeation chromatography. Cell uptake studies were carried out in KB cells (human nasopharyngeal epidermal carcinoma cell line), known to overexpress folate receptors. The uptake of folate-coated nanoparticles was about 10-fold higher than uncoated nanoparticles after 30 min at 37 degrees C. The uptake of folate-coated nanoparticles at 4 degrees C was 20-fold lower than the uptake at 37 degrees C and comparable to the uptake of uncoated nanoparticles at 37 degrees C. Folate-mediated endocytosis was further verified by the inhibition of folate-coated nanoparticles uptake by free folic acid. It was observed that folate-coated nanoparticles uptake decreased to approximately 2% of its initial value with the coincubation of 0.001 mM of free folic acid. The results suggested that these tumor-targeted nanoparticles containing high concentrations of Gd may have potential for neutron capture therapy.

  10. 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.

  11. 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.

  12. Long-circulating gadolinium-encapsulated liposomes for potential application in tumor neutron capture therapy.

    PubMed

    Le, Uyen M; Cui, Zhengrong

    2006-04-01

    Gadolinium neutron capture therapy (Gd-NCT) is a promising cancer therapy modality. One of the key factors for a successful Gd-NCT is to deliver and maintain a sufficient amount of Gd in tumor tissues during neutron irradiation. We proposed to prepare a Gd delivery system by complexing a Gd-containing compound, diethylenetriaminepentaacetic acid (Gd-DTPA), with a polycationic peptide, poly-L-lysine (pLL), and then encapsulate the complexed Gd-DTPA into PEGylated liposomes. Complexation of Gd-DTPA with pLL not only enhanced the encapsulation efficiency of Gd-DTPA in liposomes, but also significantly limited the release of Gd-DTPA from the liposomes. A Gd-DTPA-encapsulated liposome formulation that contained 6.8+/-0.3 mg/mL of pure encapsulated Gd was prepared. The blood half-life of the Gd encapsulated into the liposome formulation was estimated to be about 24 h in healthy tumor-free mice. About 12 h after the Gd-encapsulated liposomes were intravenously injected into mice with pre-established model tumors, the Gd content in the tumors reached an average of 159 microg/g of wet tumor tissue. This Gd-DTPA encapsulated liposome may be used to deliver Gd into solid tumors for NCT and tumor imaging. PMID:16457973

  13. A Project of Boron Neutron Capture Therapy System based on a Proton Linac Neutron Source

    NASA Astrophysics Data System (ADS)

    Kiyanagi, Yoshikai; Asano, Kenji; Arakawa, Akihiro; Fukuchi, Shin; Hiraga, Fujio; Kimura, Kenju; Kobayashi, Hitoshi; Kubota, Michio; Kumada, Hiroaki; Matsumoto, Hiroshi; Matsumoto, Akira; Sakae, Takeji; Saitoh, Kimiaki; Shibata, Tokushi; Yoshioka, Masakazu

    At present, the clinical trials of Boron Neutron Capture Therapy (BNCT) are being performed at research reactor facilities. However, an accelerator based BNCT has a merit that it can be built in a hospital. So, we just launched a development project for the BNCT based on an accelerator in order to establish and to spread the BNCT as an effective therapy in the near future. In the project, a compact proton linac installed in a hospital will be applied as a neutron source, and energy of the proton beam is planned to be less than about 10 MeV to reduce the radioactivity. The BNCT requires epithermal neutron beam with an intensity of around 1x109 (n/cm2/sec) to deliver the therapeutic dose to a deeper region in a body and to complete the irradiation within an hour. From this condition, the current of the proton beam required is estimated to be a few mA on average. Enormous heat deposition in the target is a big issue. We are aiming at total optimization of the accelerator based BNCT from the linac to the irradiation position. Here, the outline of the project is introduced and the moderator design is presented.

  14. 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.

  15. 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.

  16. Carborane derivatives loaded into liposomes as efficient delivery systems for boron neutron capture therapy.

    PubMed

    Altieri, S; Balzi, M; Bortolussi, S; Bruschi, P; Ciani, L; Clerici, A M; Faraoni, P; Ferrari, C; Gadan, M A; Panza, L; Pietrangeli, D; Ricciardi, G; Ristori, S

    2009-12-10

    Boron neutron capture therapy (BNCT) is an anticancer therapy based on the incorporation of (10)B in tumors, followed by neutron irradiation. Recently, the synthesis and delivery of new boronated compounds have been recognized as some of the main challenges in BNCT application. Here, we report on the use of liposomes as carriers for BNCT active compounds. Two carborane derivatives, i.e., o-closocarboranyl beta-lactoside (LCOB) and 1-methyl-o-closocarboranyl-2-hexylthioporphyrazine (H(2)PzCOB), were loaded into liposomes bearing different surface charges. The efficacy of these formulations was tested on model cell cultures, that is, DHD/K12/TRb rat colon carcinoma and B16-F10 murine melanoma. These induce liver and lung metastases, respectively, and are used to study the uptake of standard BNCT drugs, including borophenylalanine (BPA). Boron concentration in treated cells was measured by alpha spectrometry at the TRIGA mark II reactor (University of Pavia). Results showed high performance of the proposed formulations. In particular, the use of cationic liposomes increased the cellular concentration of (10)B by at least 30 times more than that achieved by BPA. PMID:19954249

  17. Medical Art Therapy: Defining a Field.

    ERIC Educational Resources Information Center

    Malchiodi, Cathy A.

    Although art therapy has traditionally focused on the use of art expression in psychotherapy, the practice of medical art therapy has begun to grow rapidly. This paper provides a brief overview of the emerging specialty of medical art therapy and its importance as a counseling tool with people suffering from serious health problems. The paper…

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

    PubMed

    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.

  19. 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.

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  1. Phase-field simulations of particle capture during the directional solidification of silicon

    NASA Astrophysics Data System (ADS)

    Aufgebauer, Henning; Kundin, Julia; Emmerich, Heike; Azizi, Maral; Reimann, Christian; Friedrich, Jochen; Jauß, Thomas; Sorgenfrei, Tina; Cröll, Arne

    2016-07-01

    We present a phase-field model for particle capture during directional solidification. Its predictions for critical growth velocities for particles of different sizes are compared with experimental results for capture of silicon carbide (SiC) particles during directional solidification of silicon. The phase-field model allows us to systematically test the influence of different assumptions about attractive and repulsive forces and the capture mechanisms, including the effects of particle shape and of partial engulfment of the particle by the interface. We identify common properties of models that show agreement with experiments, trying to determine the underlying physical effects by abductive inference. We find that predictions vary only slightly between models with different repulsive forces and that the shape of the particle can have a larger effect on the critical growth velocity than the exact nature of the repulsive force or the capture process. We assess to what extent a good description of experimental critical growth velocities implies that the model accurately describes the actual physical processes and propose additional ways to test the validity of models.

  2. 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

  3. Radiation effects of boron neutron capture therapy on brain, skin, and eye of rats

    SciTech Connect

    Matalka, K.Z.; Barth, R.F.; Bailey, M.Q.; Wilkie, D.A.; Koestner, A. ); Hopewell, J.W. )

    1994-03-30

    The present study was carried out to evaluate the radiation effects of boron neutron capture therapy (BNCT) on the brain, skin, and eyes of nude rats following systemic administration of boronophenylalanine (BPA) and neutron irradiation to the head. A solution containing 120 mg of [sup 10]B-enriched-L-BPA complexed with fructose was administered IP to nude rats. Boron concentrations were [approximately] 8.4, 9.4, 10.0, and 11.0 [mu]g/g in the brain, blood, skin, and eyes, respectively, at 6 h when the animals were irradiated at the Brookhaven Medical Research Reactor to cause tumor regression in nude rats carrying intracerebral implants of the human melanoma cell line MRA 27. Mild to moderate increases in loose fibrous tissue were observed in the choroid plexus at estimated physical doses to the brain and blood that ranged from 4.3-7.1 Gy and 4.6-7.7 Gy, respectively, and these appeared to be dose and time dependent. Other changes in the choroid plexus included occasional infiltrates of macrophages and polymorphonuclear leukocytes and vacuolation of epithelial cells. Dose-dependent moist desquamation of the skin was observed in all rats, but this had healed by 28 days following irradiation. Cataracts and keratitis developed in the eyes of most animals, and these were dose dependent. The minimal histopathological changes seen in the brain at doses that were sufficient to eradicate intracerebral melanoma indicates that BNCT has the potential to cure a tumor-bearing host without producing the normal brain injury usually associated with conventional external beam radiation therapy. Studies in canines, which currently are in progress, should further define the dose-effect relationships of BNCT on critical neuroanatomic structures within the brain. 42 refs., 4 figs., 3 tabs.

  4. Capturing field-scale variability in crop performance across a regional-scale climosequence

    NASA Astrophysics Data System (ADS)

    Brooks, E. S.; Poggio, M.; Anderson, T. R.; Gasch, C.; Yourek, M. A.; Ward, N. K.; Magney, T. S.; Brown, D. J.; Huggins, D. R.

    2014-12-01

    With the increasing availability of variable rate technology for applying fertilizers and other agrichemicals in dryland agricultural production systems there is a growing need to better capture and understand the processes driving field scale variability in crop yield and soil water. This need for a better understanding of field scale variability has led to the recent designation of the R. J. Cook Agronomy Farm (CAF) (Pullman, WA, USA) as a United States Department of Agriculture Long-Term Agro-Ecosystem Research (LTAR) site. Field scale variability at the CAF is closely monitored using extensive environmental sensor networks and intensive hand sampling. As investigating land-soil-water dynamics at CAF is essential for improving precision agriculture, transferring this knowledge across the regional-scale climosequence is challenging. In this study we describe the hydropedologic functioning of the CAF in relation to five extensively instrumented field sites located within 50 km in the same climatic region. The formation of restrictive argillic soil horizons in the wetter, cooler eastern edge of the region results in the development of extensive perched water tables, surface saturation, and surface runoff, whereas excess water is not an issue in the warmer, drier, western edge of the region. Similarly, crop and tillage management varies across the region as well. We discuss the implications of these regional differences on field scale management decisions and demonstrate how we are using proximal soil sensing and remote sensing imagery to better understand and capture field scale variability at a particular field site.

  5. A Novel Method of Boron Delivery Using Sodium Iodide Symporter for Boron Neutron Capture Therapy

    PubMed Central

    KUMAR, Sanath; FREYTAG, Svend O.; BARTON, Kenneth N.; BURMEISTER, Jay; JOINER, Michael C.; SEDGHI, Bijan; MOVSAS, Benjamin; BINNS, Peter J.; KIM, Jae Ho; BROWN, Stephen L.

    2013-01-01

    Boron Neutron Capture Therapy (BNCT) effectiveness depends on the preferential sequestration of boron in cancer cells relative to normal tissue cells. We present a novel strategy for sequestering boron using an adenovirus expressing the sodium iodide symporter (NIS). Human glioma grown subcutaneously in athymic mice and orthotopic rat brain tumors were transfected with NIS using a direct tumor injection of adenovirus. Boron bound as sodium tetrafluoroborate (NaBF4) was administered systemically several days after transfection. Tumors were excised hours later and assessed for boron concentration using inductively coupled plasma atomic emission spectroscopy. In the human glioma transfected with NIS, boron concentration was more than 10 fold higher with 100 mg/kg of NaBF4, compared to tumor not transfected. In the orthotopic tumor model, the presence of NIS conferred almost 4 times the boron concentration in rat tumors transfected with human virus compared with contralateral normal brain not transfected. We conclude that adenovirus expressing NIS has the potential to be used as a novel boron delivery agent and should be explored for future clinical applications. PMID:20921830

  6. Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas

    PubMed Central

    Miyatake, Shin-Ichi; Kawabata, Shinji; Nonoguchi, Naosuke; Yokoyama, Kunio; Kuroiwa, Toshihiko; Matsui, Hideki; Ono, Koji

    2009-01-01

    Pseudoprogression has been recognized and widely accepted in the treatment of malignant gliomas, as transient increases in the volume of the enhanced area just after chemoradiotherapy, especially using temozolomide. We experienced a similar phenomenon in the treatment of malignant gliomas and meningiomas using boron neutron capture therapy (BNCT), a cell-selective form of particle radiation. Here, we introduce representative cases and analyze the pathogenesis. Fifty-two cases of malignant glioma and 13 cases of malignant meningioma who were treated by BNCT were reviewed retrospectively mainly via MR images. Eleven of 52 malignant gliomas and 3 of 13 malignant meningiomas showed transient increases of enhanced volume in MR images within 3 months after BNCT. Among these cases, five patients with glioma underwent surgery because of suspicion of relapse. In histology, most of the specimens showed necrosis with small amounts of residual tumor cells. Ki-67 labeling showed decreased positivity compared with previous samples from the individuals. Fluoride-labeled boronophenylalanine PET was applied in four and two cases of malignant gliomas and meningiomas, respectively, at the time of transient increase of lesions. These PET scans showed decreased lesion:normal brain ratios in all cases compared with scans obtained prior to BNCT. With or without surgery, all lesions were decreased or stable in size during observation. Transient increases in enhanced volume in malignant gliomas and meningiomas immediately after BNCT seemed to be pseudoprogression. This pathogenesis was considered as treatment-related intratumoral necrosis in the subacute phase after BNCT. PMID:19289492

  7. 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.

  8. 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

  9. 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.

  10. Designing accelerator-based epithermal neutron beams for boron neutron capture therapy

    SciTech Connect

    Bleuel, D.L. |; Donahue, R.J.; Ludewigt, B.A.; Vujic, J.

    1998-09-01

    The {sup 7}Li(p,n){sup 7}Be reaction has been investigated as an accelerator-driven neutron source for proton energies between 2.1 and 2.6 MeV. Epithermal neutron beams shaped by three moderator materials, Al/AlF{sub 3}, {sup 7}LiF, and D{sub 2}O, have been analyzed and their usefulness for boron neutron capture therapy (BNCT) treatments evaluated. Radiation transport through the moderator assembly has been simulated with the Monte Carlo {ital N}-particle code (MCNP). Fluence and dose distributions in a head phantom were calculated using BNCT treatment planning software. Depth-dose distributions and treatment times were studied as a function of proton beam energy and moderator thickness. It was found that an accelerator-based neutron source with Al/AlF{sub 3} or {sup 7}LiF as moderator material can produce depth-dose distributions superior to those calculated for a previously published neutron beam design for the Brookhaven Medical Research Reactor, achieving up to {approximately}50{percent} higher doses near the midline of the brain. For a single beam treatment, a proton beam current of 20 mA, and a {sup 7}LiF moderator, the treatment time was estimated to be about 40 min. The tumor dose deposited at a depth of 8 cm was calculated to be about 21 Gy-Eq. {copyright} {ital 1998 American Association of Physicists in Medicine.}

  11. Monte Carlo simulation of depth dose distribution in several organic models for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Matsumoto, T.

    2007-09-01

    Monte Carlo simulations are performed to evaluate depth-dose distributions for possible treatment of cancers by boron neutron capture therapy (BNCT). The ICRU computational model of ADAM & EVA was used as a phantom to simulate tumors at a depth of 5 cm in central regions of the lungs, liver and pancreas. Tumors of the prostate and osteosarcoma were also centered at the depth of 4.5 and 2.5 cm in the phantom models. The epithermal neutron beam from a research reactor was the primary neutron source for the MCNP calculation of the depth-dose distributions in those cancer models. For brain tumor irradiations, the whole-body dose was also evaluated. The MCNP simulations suggested that a lethal dose of 50 Gy to the tumors can be achieved without reaching the tolerance dose of 25 Gy to normal tissue. The whole-body phantom calculations also showed that the BNCT could be applied for brain tumors without significant damage to whole-body organs.

  12. Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

    PubMed

    Saha, Tapan Kumar; Ichikawa, Hideki; Fukumori, Yoshinobu

    2006-12-11

    In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection. PMID:17045253

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Manual vs. automatic capture management in implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators

    PubMed Central

    Murgatroyd, Francis D.; Helmling, Erhard; Lemke, Bernd; Eber, Bernd; Mewis, Christian; van der Meer-Hensgens, Judith; Chang, Yanping; Khalameizer, Vladimir; Katz, Amos

    2010-01-01

    Aims The Secura™ ICD and Consulta™ CRT-D are the first defibrillators to have automatic right atrial (RA), right ventricular (RV), and left ventricular (LV) capture management (CM). Complete CM was evaluated in an implantable cardioverter defibrillator (ICD) population. Methods and results Two prospective clinical studies were conducted in 28 centres in Europe and Israel. Automatic CM data were compared with manual threshold measurements, the CM applicability was determined, and adjustments to pacing outputs were analysed. In total, 160 patients [age 64.6 ± 10.4 years, 77% male, 80 ICD and 80 cardiac resynchronization therapy defibrillator (CRT-D)] were included. The differences between automatic and manual measurements were ≤0.25 V in 97% (RA CM) and 96% (RV CM) and were all within the safety margin. Fully automatic CM measurements were available within 1 week prior to the 3-month visit in 90% (RA), 99% (RV), and 97% (LV) of the patients. Results indicated increased output (threshold >2.5 V) due to raised RA threshold in seven (4.4%), high RV threshold in nine (5.6%), and high LV threshold in three patients (3.8%). All high threshold detections and all automatic modulations of pacing output were adjudicated appropriate. Conclusion Complete CM adjusts pacing output appropriately, permitting a reduction in office visits while it may maximize device longevity. The study was registered at ClinicalTrials.gov identifiers: NCT00526227 and NCT00526162. PMID:20231152

  19. Sonoporation as an enhancing method for boron neutron capture therapy for squamous cell carcinomas

    PubMed Central

    2013-01-01

    Background Boron neutron capture therapy (BNCT) is a selective radiotherapy that is dependent on the accumulation of 10B compound in tumors. Low-intensity ultrasound produces a transient pore on cell membranes, sonoporation, which enables extracellular materials to enter cells. The effect of sonoporation on BNCT was examined in oral squamous cell carcinoma (SCC) xenografts in nude mice. Materials and methods Tumor-bearing mice were administrated boronophenylalanine (BPA) or boronocaptate sodium (BSH) intraperitoneally. Two hours later, tumors were subjected to sonoporation using microbubbles followed by neutron irradiation. Results The 10B concentration was higher in tumors treated with sonoporation than in untreated tumors, although the difference was not significant in BPA. When tumors in mice that received BPA intraperitoneally were treated with sonoporation followed by exposure to thermal neutrons, tumor volume was markedly reduced and the survival rate was prolonged. Such enhancements by sonoporation were not observed in mice treated with BSH-mediated BNCT. Conclusions These results indicate that sonoporation enhances the efficiency of BPA-mediated BNCT for oral SCC. Sonoporation may modulate the microlocalization of BPA and BSH in tumors and increase their intracellular levels. PMID:24295213

  20. 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.

  1. Selective ablation of rat brain tumors by boron neutron capture therapy

    SciTech Connect

    Coderre, J.; Joel, D. ); Rubin, P.; Freedman, A.; Hansen, J.; Wooding, T.S. Jr.; Gash, D. )

    1994-03-30

    Damage to the surrounding normal brain tissue limits the amount of radiation that can be delivered to intracranial tumors. Boron neutron capture therapy (BNCT) is a binary treatment that allows selective tumor irradiation. This study evaluates the damage imparted to the normal brain during BNCT or x-irradiation. The brains of rats with implanted 9L gliosarcomas were examined 1 year after tumor-curative doses of either 250 kV X-rays or BNCT. Histopathologic techniques included hematoxylin and eosin staining, horseradish peroxidase perfusion, and electron microscopy. Longterm X-ray survivors showed extensive cortical atrophy, loss of neurons, and widespread leakage of the blood-brain barrier (BBB), particularly around the tumor scar. In contrast, the brains and the BBB of longterm BNCT survivors appeared relatively normal under both light- and electron-microscopic examination. Intact blood vessels were observed running directly through the avascular, collagenous tumor scar. The selective therapeutic effect of BNCT is evident in comparison to x-irradiation. Both groups of animals showed no evidence of residual tumor at 1 year. However, with x-irradiation there is no therapeutic ratio and tumor eradication severely injuries the remaining brain parenchyma. These observations indicate a substantial therapeutic gain for BNCT. 50 refs., 8 figs., 1 tab.

  2. High-power liquid-lithium target prototype for accelerator-based boron neutron capture therapy.

    PubMed

    Halfon, S; Paul, M; Arenshtam, A; Berkovits, D; Bisyakoev, M; Eliyahu, I; Feinberg, G; Hazenshprung, N; Kijel, D; Nagler, A; Silverman, I

    2011-12-01

    A prototype of a compact Liquid-Lithium Target (LiLiT), which will possibly constitute an accelerator-based intense neutron source for Boron Neutron Capture Therapy (BNCT) in hospitals, was built. The LiLiT setup is presently being commissioned at Soreq Nuclear Research Center (SNRC). The liquid-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 generated using a high-intensity proton beam (>10 kW), necessary for sufficient neutron flux. In off-line circulation tests, the liquid-lithium loop generated a stable lithium jet at high velocity, on a concave supporting wall; the concept will first be tested using a high-power electron beam impinging on the lithium jet. High intensity proton beam irradiation (1.91-2.5 MeV, 2-4 mA) will take place at Soreq Applied Research Accelerator Facility (SARAF) superconducting linear accelerator currently in construction at SNRC. Radiological risks due to the (7)Be produced in the reaction were studied and will be handled through a proper design, including a cold trap and appropriate shielding. A moderator/reflector assembly is planned according to a Monte Carlo simulation, to create a neutron spectrum and intensity maximally effective to the treatment and to reduce prompt gamma radiation dose risks.

  3. 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.

  4. Boronated monoclonal antibody 225. 28S for potential use in neutron capture therapy of malignant melanoma

    SciTech Connect

    Tamat, S.R.; Moore, D.E.; Patwardhan, A.; Hersey, P. )

    1989-07-01

    The concept of conjugating boron cluster compounds to monoclonal antibodies has been examined by several groups of research workers in boron neutron capture therapy (BNCT). The procedures reported to date for boronation of monoclonal antibodies resulted in either an inadequate level of boron incorporation, the precipitation of the conjugates, or a loss of immunological activity. The present report describes the conjugation of dicesium-mercapto-undecahydrododecaborate (Cs2B12H11SH) to 225.28S monoclonal antibody directed against high molecular weight melanoma-associated antigens (HMW-MAA), using poly-L-ornithine as a bridge to increase the carrying capacity of the antibody and to minimize change in the conformational structure of antibody. The method produces a boron content of 1,300 to 1,700 B atoms per molecule 225.28S while retaining the immunoreactivity. Characterization in terms of the homogeneity of the conjugation of the boron-monoclonal antibody conjugates has been studied by gel electrophoresis and ion-exchange HPLC.

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

    PubMed

    Brandão, Sâmia F; Campos, Tarcísio P R

    2012-04-01

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

  6. Experimental Research on the Capture of Fine Particles in a High-voltage Electric Field

    NASA Astrophysics Data System (ADS)

    Jin, Xing; Li, Shuiqing

    2015-11-01

    Mechanisms for capturing of fine particles through a high-voltage electric field were examined using the electrostatic precipitator (ESP) as an example system. The dimensionless equations governing particle transport were solved and a laboratory-scale ESP was experimentally examined. The analysis indicates that particles in the size range of 0.1-1 μm have the lowest electric migration velocity and there is a capture-effective zone in the middle of the ESP for fine particles. Subsequent increase in length had little effect for grade efficiency because of the influence of electrohydrodynamic (EHD) flow. In the particle boundary layer zone, dipole-dipole force and VDW force play crucial roles in capturing fine particles. The packing structure of fine particles on the collecting plate is investigated by digital microscopy technology. The effects of pre-charging, pre-polarization and external electric field on packing morphologies are discussed. It is found that the dipole-dipole force between particles causes the formation of long particle chains and the maximum length of particle dendrites during the packing is dependent on both the density of external field and deposit structure.

  7. 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.

  8. Pharamacokinetic modeling for boronophenylalanine-fructose mediated neutron capture therapy: 10B concentration predictions and dosimetric consequences.

    PubMed

    Kiger, W S; Palmer, M R; Riley, K J; Zamenhof, R G; Busse, P M

    2003-01-01

    A two-compartment open model has been developed for predicting 10B concentrations in blood following intravenous infusion of the L-p-boronophenylalanine-fructose complex in humans and derived from pharmacokinetic studies of 24 patients in Phase I clinical trials of boron neutron capture therapy. The 10B concentration profile in blood exhibits a characteristic rise during the infusion to a peak of approximately 32 microg/g (for infusion of 350 mg/kg over 90 min) followed by a biexponential disposition profile with harmonic mean half-lives of 0.32 +/- 0.08 and 8.2 +/- 2.7 h, most likely due to redistribution and primarily renal elimination, respectively. The mean model rate constants k12, k21, and k10 are (mean +/- SD) 0.0227 +/- 0.0064 min(-1), 0.0099 +/- 0.0027 min(-1), 0.0052 +/- 0.0016 min(-1), respectively, and the central compartment volume of distribution V1 is 0.235 +/- 0.042 L/kg. In anticipation of the initiation of clinical trials using an intense neutron beam with concomitantly short irradiations, the ability of this model to predict, in advance, the average blood 10B concentration during brief irradiations was simulated in a retrospective analysis of the pharmacokinetic data from these patients. The prediction error for blood boron concentration and its effect on simulated dose delivered for each irradiation field are reported for three different prediction strategies. In this simulation, error in delivered dose (or, equivalently, neutron fluence) for a given single irradiation field resulting from error in predicted blood 10B concentration was limited to less than 10%. In practice, lower dose errors can be achieved by delivering each field in two fractions (on two separate days) and by adjusting the second fraction's dose to offset error in the first.

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

    NASA Astrophysics Data System (ADS)

    Sakurai, Yoshinori; Kobayashi, Tooru

    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.

  10. 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.

  11. 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

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

    SciTech Connect

    Nigg, David W.; Wemple, Charles A.; Risler, Ruedi; Hartwell, John K.; Harker, Yale D.; Laramore, George 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

  13. Extended Field Laser Confocal Microscopy (EFLCM): Combining automated Gigapixel image capture with in silico virtual microscopy

    PubMed Central

    Flaberg, Emilie; Sabelström, Per; Strandh, Christer; Szekely, Laszlo

    2008-01-01

    Background Confocal laser scanning microscopy has revolutionized cell biology. However, the technique has major limitations in speed and sensitivity due to the fact that a single laser beam scans the sample, allowing only a few microseconds signal collection for each pixel. This limitation has been overcome by the introduction of parallel beam illumination techniques in combination with cold CCD camera based image capture. Methods Using the combination of microlens enhanced Nipkow spinning disc confocal illumination together with fully automated image capture and large scale in silico image processing we have developed a system allowing the acquisition, presentation and analysis of maximum resolution confocal panorama images of several Gigapixel size. We call the method Extended Field Laser Confocal Microscopy (EFLCM). Results We show using the EFLCM technique that it is possible to create a continuous confocal multi-colour mosaic from thousands of individually captured images. EFLCM can digitize and analyze histological slides, sections of entire rodent organ and full size embryos. It can also record hundreds of thousands cultured cells at multiple wavelength in single event or time-lapse fashion on fixed slides, in live cell imaging chambers or microtiter plates. Conclusion The observer independent image capture of EFLCM allows quantitative measurements of fluorescence intensities and morphological parameters on a large number of cells. EFLCM therefore bridges the gap between the mainly illustrative fluorescence microscopy and purely quantitative flow cytometry. EFLCM can also be used as high content analysis (HCA) instrument for automated screening processes. PMID:18627634

  14. 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.

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

    PubMed

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

    2012-02-01

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

  16. Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy

    SciTech Connect

    Goodman, J.H.; McGregor, J.M.; Clendenon, N.R.; Gahbauer, R.A.; Barth, R.F.; Soloway, A.H.; Fairchild, R.G. )

    1990-09-01

    This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity.

  17. Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

    PubMed Central

    MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

    2014-01-01

    The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

  18. 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.

  19. Melanogenesis investigation leading to selective melanoma neutron capture therapy and diagnosis.

    PubMed

    Mishima, Y

    1994-11-01

    Basic investigation into the nature of melanin monomer and polymer synthesis in pigment cells has revealed many of the new underlying factors involved in its regulation and control by three melanogenesis-related genes, tyrosinase, TRP-1 and TRP-2, and other non-tyrosinase glycoproteins. Pigment cells can undergo clinically and biologically recognizable progressive multi-step carcinogenesis. Generally parallel to this progressive cancerization is accentuated melanogenesis. Using this accentuated melanogenesis to develop a specific diagnosis and cure for melanoma (Mm) has long been a challenge. However, until recently, no success was achieved. As an example, attempting to utilize the fact that dopa accumulates as a melanin substrate within Mm cells, hybrid compounds of dopa and cytotoxic drugs were developed. However, these compounds were found to have severe systemic side effects and were therefore unusable. Another newer Mm treatment involves high energy radiation such as fast neutrons. But this is quite non-selective, killing both the target cancer and the normal surrounding tissue. Since 1972, I have developed the idea of coupling the high energy releasing system of thermal neutron irradiation with the non-toxic 10B-dopa analogue, 10B1-L-p-boronophenylalanine (10B1-L-BPA). Thermal neutrons are essentially harmless, but, after specific absorption by 10B, release high LET alpha-particles and 7Li-atoms with an energy of 2.33 MeV up to a distance of 14 mu, the diameter of Mm cells, thus selectively killing them without damaging surrounding normal tissue. After the synthesis of 10B1-L-BPA, exhaustive in vitro and in vivo radiological studies on its enhanced killing effect were done to develop optimal Mm Boron Neutron Capture Therapy (NCT).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Effect of boron neutron capture therapy for melanotic and amelanotic melanoma transplanted into mouse brain.

    PubMed

    Iwakura, Masaki; Kondoh, Hirofumi; Hiratsuka, Junichi; Ehara, Kazumasa; Tamaki, Norihiko; Mishima, Yutaka

    2002-02-01

    In order to develop a protocol to treat brain metastatic melanoma using our 10B-p-boronophenylalanine (BPA) boron neutron capture therapy (BNCT), we initiated the following studies (i), Comparative analyses of boron biodistribution between melanoma proliferating in the brain and skin among melanotic and amelanotic types, and (ii) Therapeutic evaluation of BPA-BNCT for brain melanoma models of both types, using survival times. Our present data have revealed that boron concentration in melanoma proliferating in the brain, the major prerequisite for successful BNCT, showed a positive correlation to melanin synthesizing activity in the same way as melanoma proliferating in skin. Further, the boron concentration ratio of melanoma to normal surrounding tissue for brain melanoma models was considerably higher than that for subcutaneous (s.c.) ones because of the existence of the blood-brain barrier (BBB). Additionally, from analyses of median and mean survival times following BNCT using low, middle, and high neutron doses, the therapeutic effect of BNCT for the amelanotic A1059 melanoma appeared at first glance to be higher than that for the highly BPA attracting and highly relative biological effect equivalent dose obtaining B15b melanoma. As the survival time was dependent on both regression and regrowth curves, and because the brain melanoma model in small animals made it difficult to evaluate these curves separately, we further examined the in vivo growth curve of both types of melanomas following implantation in s.c. tissue. The melanotic B15b melanoma was indeed found to possess much higher growth rate as compared with that of the amelanotic A1059 melanoma. The significance of boron biodistribution studies and BNCT survival curve analyses in forming an effective clinical protocol for individual human cases of melanoma brain metastasis is discussed.

  1. The combined effect of electroporation and borocaptate in boron neutron capture therapy for murine solid tumors.

    PubMed

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

    2000-08-01

    10 B-Enriched borocaptate (BSH) was administered intraperitoneally to SCCVII tumor-bearing C3H / He mice. Electroporation (EP) was conducted by using a tweezers-type electrode. The (10) B contents in tumors were measured by prompt gamma-ray spectrometry. The colony formation assay was applied to investigate the antitumor effects of boron neutron capture therapy (BNCT) and thereby to estimate the intratumor localization of BSH. The (10) B concentrations in tumors decreased with time following BSH administration, falling to 5.4(0. 1) ppm at 3 h, whereas EP treatment (3 repetitions) 15 min after BSH injection delayed the clearance of BSH from tumors, and the (10) B level remained at 19.4(0.9) ppm at 3 h. The effect of BNCT increased with the (10) B concentration in tumors, and the combination with EP showed a remarkably large cell killing effect even at 3 h after BSH injection. The effect of BNCT, i.e., slope coefficient of the cell survival curve of tumors, without EP was proportional to tumor (10) B level (r = 0.982), and that of BSH-BNCT combined with EP lay close to the same correlation line. However, tumors subjected to EP after BSH injection did not show high radiosensitivity when irradiated after conversion to a single cell suspension by enzymatic digestion. This indicates that the increase of the BNCT effect by EP was a consequence of enclosure of BSH in the interstitial space of tumor tissue and not within tumor cells. This is different from a previous in vitro study. The combination of EP and BNCT may be clinically useful, if a procedure to limit EP to the tumor region becomes available or if an alternative similar method is employed. PMID:10965028

  2. 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.

  3. 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.

  4. Radiobiology of boron neutron capture therapy: Problems with the concept of relative biological effectiveness

    SciTech Connect

    Coderre, J.A.; Makar, M.S.

    1990-01-01

    The radiation dose delivered to cells in vitro or vivo during boron neutron capture therapy (BNCT) is a mixture of photons, fast neutrons and heavy charged particles from the interaction of neutrons with nitrogen and born. The concept of relative biological effectiveness (RBE) had been developed to allow comparison of the effects of these radiations with the effects of standard photon treatments such as 250 kVp x-rays or {sup 60}Co gamma rays. The RBE value for all of these high linear energy transfer radiations can vary considerably depending upon the experimental conditions and endpoint utilized. The short range of the particles from the {sup 10}B(n,{alpha}) {sup 7}Li reaction make the precise subcellular location of the {sup 10}B atom of critical importance. The microscopic distribution of the {sup 10}B has a decided effect on the dosimetry. Monte Carlo simulations have shown that, at the cellular level, there is a profound difference in the probability of cell kill depending on the location of the {sup 10}B relative to the nucleus. Different boron-delivery agents will almost certainly have different distribution patterns at the subcellular level. The effect of BNCT with the amino acid p-boronophenylalanine (BPA) was compared with the effect of 250 kVp x-rays on a pigmented B16 melanoma subclone, both in vitro and in vivo. Generally accepted RBE values were applied to the relevant components of the Brookhaven Medical Research Reactor (BMRR) thermal neutron beam, however, there were still discrepancies when the resulting dose response curves were compared with the response to 250 kVp x-rays.

  5. 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.

  6. 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

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

    SciTech Connect

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

    1992-05-01

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

  8. 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.

  9. 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

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

    PubMed

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

    2006-11-20

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

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

    PubMed

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

    2006-11-20

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

  12. Biomaterials and Magnetic fields for Cancer Therapy

    NASA Technical Reports Server (NTRS)

    Ramachandran, Narayanan; Mazuruk, Konstanty

    2003-01-01

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

  13. Reference dosimetry calculations for neutron capture therapy with comparison of analytical and voxel models.

    PubMed

    Goorley, J T; Kiger, W S; Zamenhof, R G

    2002-02-01

    As clinical trials of Neutron Capture Therapy (NCT) are initiated in the U.S. and other countries, new treatment planning codes are being developed to calculate detailed dose distributions in patient-specific models. The thorough evaluation and comparison of treatment planning codes is a critical step toward the eventual standardization of dosimetry, which, in turn, is an essential element for the rational comparison of clinical results from different institutions. In this paper we report development of a reference suite of computational test problems for NCT dosimetry and discuss common issues encountered in these calculations to facilitate quantitative evaluations and comparisons of NCT treatment planning codes. Specifically, detailed depth-kerma rate curves were calculated using the Monte Carlo radiation transport code MCNP4B for four different representations of the modified Snyder head phantom, an analytic, multishell, ellipsoidal model, and voxel representations of this model with cubic voxel sizes of 16, 8, and 4 mm. Monoenergetic and monodirectional beams of 0.0253 eV, 1, 2, 10, 100, and 1000 keV neutrons, and 0.2, 0.5, 1, 2, 5, and 10 MeV photons were individually simulated to calculate kerma rates to a statistical uncertainty of <1% (1 std. dev.) in the center of the head model. In addition, a "generic" epithermal neutron beam with a broad neutron spectrum, similar to epithermal beams currently used or proposed for NCT clinical trials, was computed for all models. The thermal neutron, fast neutron, and photon kerma rates calculated with the 4 and 8 mm voxel models were within 2% and 4%, respectively, of those calculated for the analytical model. The 16 mm voxel model produced unacceptably large discrepancies for all dose components. The effects from different kerma data sets and tissue compositions were evaluated. Updating the kerma data from ICRU 46 to ICRU 63 data produced less than 2% difference in kerma rate profiles. The depth-dose profile data

  14. 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.

  15. 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.

  16. Standard Extraction Methods May Underestimate Nitrate Stocks Captured by Field-Aged Biochar.

    PubMed

    Haider, Ghulam; Steffens, Diedrich; Müller, Christoph; Kammann, Claudia I

    2016-07-01

    Biochar (BC) has been shown to increase the potential for N retention in agricultural soils. However, the form of N retained and its strength of retention are poorly understood. Here, we examined if the N retained could be readily extractable by standard methods and if the amount of N retained varied with BC field ageing. We investigated soil and field-aged BC (BC) particles of a field experiment (sandy soil amended with BC at 0, 15, and 30 t ha) under two watering regimes (irrigated and rain-fed). Throughout the study, greater nitrate than ammonium retention was observed with BC addition in topsoil (0-15 cm). Subsoil (15-30 cm) nitrate concentrations were reduced in BC treatments, indicating reduced nitrate leaching (standard 2 mol L KCl method). The mineral-N release of picked BC particles was examined with different methods: standard 2 mol L KCl extraction; repeated (10×) extraction in 2 mol L KCl at 22 ± 2°C and 80°C (M); electro-ultrafiltration (M); repeated water + KCl long-term shaking (M); and M plus one repeated shaking at 80°C (M). Nitrate amounts captured by BC particles were several-fold greater than those in the BC-amended soil. Compared with M, standard 2 mol L KCl or electro-ultrafiltration extractions retrieved only 13 and 30% of the total extractable nitrates, respectively. Our results suggest that "nitrate capture" by BC may reduce nitrate leaching in the field and that the inefficiency of standard extraction methods deserves closer research attention to decipher mechanisms for reactive N management. PMID:27380067

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

    NASA Astrophysics Data System (ADS)

    Romanov, Dmitri; Auner, Gregory

    2001-03-01

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

  18. 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.

  19. Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

    PubMed Central

    2010-01-01

    Background Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation. Methods The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical University (FMMU) in China. Human glioma cells (the U87, U251, and SHG44 cell lines) were irradiated by neutron beams at the XAPR or [60Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [60Co] γ-rays; Group C included cells treated with 8 Gy of [60Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine)-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM). The apoptosis rate was detected by flow cytometer (FCM). The level of Bcl-2 and Bax protein was measured by western blot analysis. Results Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [60Co] γ-rays (P < 0.01). Nuclear condensation was determined using both a fluorescence technique and electron microscopy in all cell lines treated with BPA-BNCT. Furthermore, the cellular apoptotic rates in Group D and Group E

  20. Combination of the vascular targeting agent ZD6126 with boron neutron capture therapy

    SciTech Connect

    Masunaga, Shin-ichiro . E-mail: smasuna@rri.kyoto-u.ac.jp; Sakurai, Yoshinori; Suzuki, Minoru; Nagata, Kenji; Maruhashi, Akira; Kinash, Yuko; Ono, Koji

    2004-11-01

    Purpose: The aim of this study was to evaluate the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) in the rodent squamous cell carcinoma (SCC) VII carcinoma model, in combination with boron neutron capture therapy (BNCT). Methods and materials: Sodium borocaptate-{sup 10}B (BSH, 125 mg/kg, i.p.) or l-p-boronophenylalanine-{sup 10}B (BPA, 250 mg/kg, i.p.) was injected into SCC VII tumor-bearing mice, and 15 min later, ZD6126 (100 mg/kg, i.p.) was administered. Then, the {sup 10}B concentrations in tumors and normal tissues were measured by prompt {gamma}-ray spectrometry. On the other hand, for the thermal neutron beam exposure experiment, SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, followed by treatment with a {sup 10}B-carrier and ZD6126 in the same manner as the above-mentioned {sup 10}B pharmacokinetics analyses. To obtain almost similar intratumor {sup 10}B concentrations during neutron exposure, thermal neutron beam irradiation was started from the time point of 30 min after injection of BSH only, 90 min after BSH injection for combination with ZD6126, 120 min after the injection of BPA only, and 180 min after BPA injection for combination with ZD6126. Right after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (quiescent [Q] cells) was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. The clonogenic cell survival assay was also performed in mice given no BrdU. Results: Pharmacokinetics analyses showed that combination with ZD6126 greatly increased the {sup 10}B concentrations in tumors after 60 min after BSH injection and

  1. 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

  2. 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.

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

    SciTech Connect

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

    2012-01-01

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

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

    PubMed

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

    2012-02-01

    The muon-capture reactions {2}H(μ{-},ν{μ})nn and {3}He(μ{-},ν{μ}){3}H are studied with nuclear potentials and charge-changing weak currents, derived in chiral effective field theory. The low-energy constants (LECs) c{D} and c{E}, present in the three-nucleon potential and (c{D}) axial-vector current, are constrained to reproduce the A=3 binding energies and the triton Gamow-Teller matrix element. The muon-capture rates on deuteron and {3}He are predicted to be 399±3  sec{-1} and 1494±21  sec{-1}, respectively. The spread accounts for the cutoff sensitivity, as well as uncertainties in the LECs and electroweak radiative corrections. By comparing the calculated and precisely measured rates on {3}He, a value for the induced pseudoscalar form factor is obtained in good agreement with the chiral perturbation theory prediction. PMID:22400928

  6. 10B-editing 1H-detection and 19F MRI strategies to optimize boron neutron capture therapy.

    PubMed

    Capuani, Silvia; Porcari, Paola; Fasano, Fabrizio; Campanella, Renzo; Maraviglia, Bruno

    2008-09-01

    Boron neutron capture therapy (BNCT) is a binary radiation therapy used to treat malignant brain tumours. It is based on the nuclear reaction (10B + n th --> [11B*] --> alpha + 7Li + 2.79 MeV) that occurs when 10B captures a thermal neutron to yield alpha particles and recoiling 7Li nuclei, both responsible of tumour cells destruction by short range and high ionization energy release. The clinical success of the therapy depends on the selective accumulation of the 10B carriers in the tumour and on the high thermal neutron capture cross-section of 10B. Magnetic resonance imaging (MRI) methods provide the possibility of monitoring, through 10B nuclei, the metabolic and physiological processes suitable to optimize the BNCT procedure. In this study, spatial distribution mapping of borocaptate (BSH) and 4-borono-phenylalanine (BPA), the two boron carriers used in clinical trials, has been obtained. The BSH map in excised rat brain and the 19F-BPA image in vivo rat brain, representative of BPA spatial distribution, were reported. The BSH image was obtained by means of double-resonance 10B-editing 1H-detection sequence, named M-Bend, exploiting the J-coupling interaction between 10B and 1H nuclei. Conversely, the BPA map was obtained by 19F-BPA using 19F-MRI. Both images were obtained at 7 T, in C6 glioma-bearing rat brain. Our results demonstrate the powerful of non conventional MRI techniques to optimize the BNCT procedure.

  7. 10B-editing 1H-detection and 19F MRI strategies to optimize boron neutron capture therapy.

    PubMed

    Capuani, Silvia; Porcari, Paola; Fasano, Fabrizio; Campanella, Renzo; Maraviglia, Bruno

    2008-09-01

    Boron neutron capture therapy (BNCT) is a binary radiation therapy used to treat malignant brain tumours. It is based on the nuclear reaction (10B + n th --> [11B*] --> alpha + 7Li + 2.79 MeV) that occurs when 10B captures a thermal neutron to yield alpha particles and recoiling 7Li nuclei, both responsible of tumour cells destruction by short range and high ionization energy release. The clinical success of the therapy depends on the selective accumulation of the 10B carriers in the tumour and on the high thermal neutron capture cross-section of 10B. Magnetic resonance imaging (MRI) methods provide the possibility of monitoring, through 10B nuclei, the metabolic and physiological processes suitable to optimize the BNCT procedure. In this study, spatial distribution mapping of borocaptate (BSH) and 4-borono-phenylalanine (BPA), the two boron carriers used in clinical trials, has been obtained. The BSH map in excised rat brain and the 19F-BPA image in vivo rat brain, representative of BPA spatial distribution, were reported. The BSH image was obtained by means of double-resonance 10B-editing 1H-detection sequence, named M-Bend, exploiting the J-coupling interaction between 10B and 1H nuclei. Conversely, the BPA map was obtained by 19F-BPA using 19F-MRI. Both images were obtained at 7 T, in C6 glioma-bearing rat brain. Our results demonstrate the powerful of non conventional MRI techniques to optimize the BNCT procedure. PMID:18486394

  8. 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.

  9. Radiowave dielectric investigation of boron compounds distribution in cultured tumour cells: relevance to boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Capuani, S.; Gili, T.; Cametti, C.; Maraviglia, B.; Colasanti, M.; Muolo, M.; Venturini, G.

    2002-07-01

    The distribution of two main Boron neutron capture therapy (BNCT) agents, borocaptate sodium ( BSH) and borono-phenylalanine ( BPA), in C6 rat glioma cells has been investigated by means of radiowave dielectric spectroscopy measurements. Significant differences between cells treated with the two different boron carriers were found in the magnitude of passive electrical cell parameters. This technique offers a new procedure for the measurement of boron compounds interactions with different biological environments at cellular level and is suggested to have the potentiality for becoming an attractive tool for biodistribution studies of BNCT compounds in biological tissues.

  10. 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.

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

    DOEpatents

    Peurrung, Anthony J.

    1997-01-01

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

  12. 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. 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.

  14. 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.

  15. 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.

  16. 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).

  17. The radiobiological principles of boron neutron capture therapy: a critical review.

    PubMed

    Hopewell, J W; Morris, G M; Schwint, A; Coderre, J A

    2011-12-01

    The radiobiology of the dose components in a BNCT exposure is examined. The effect of exposure time in determining the biological effectiveness of γ-rays, due to the repair of sublethal damage, has been largely overlooked in the application of BNCT. Recoil protons from fast neutrons vary in their relative biological effectiveness (RBE) as a function of energy and tissue endpoint. Thus the energy spectrum of a beam will influence the RBE of this dose component. Protons from the neutron capture reaction in nitrogen have not been studied but in practice protons from nitrogen capture have been combined with the recoil proton contribution into a total proton dose. The relative biological effectiveness of the products of the neutron capture reaction in boron is derived from two factors, the RBE of the short range particles and the bio-distribution of boron, referred to collectively as the compound biological effectiveness factor. Caution is needed in the application of these factors for different normal tissues and tumors. PMID:21543233

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  19. Structural investigation of naturally occurring peptides by electron capture dissociation and AMBER force field modelling

    NASA Astrophysics Data System (ADS)

    Polfer, Nick C.; Haselmann, Kim F.; Langridge-Smith, Pat R. R.; Barran, Perdita E.

    We present a detailed analysis of the relative yields in dissociation products of doubly protonated polypeptide cations obtained via electron capture dissociation (ECD). These experimental studies are complemented by molecular dynamics force field modelling, using the AMBER force field, to correlate with putative gas-phase conformations for these peptides. It is shown that the highest gas-phase basicity amino acid residue (i.e. arginine) is included in all the charged fragments. This is of particular use in determining the primary structure tryptic digest peptides, which will ordinarily posses a high basicity C-terminal residue (i.e. arginine or lysine). Further, these results suggest that the relative ECD dissociation pattern is related to the secondary structure of the peptide. In particular, the ECD fragmentation pattern in gonadatropin releasing hormone (GnRH) variants appears to depend on whether a β-turn or an extended α-helical structure is formed. In the peptide bradykinin, modelling suggests that the C-terminal arginine engages in much more extended solvation of the backbone than the N-terminal arginine. This strongly correlates with the observed dominance of c over z fragments. This work forms the first attempt at a systematic qualitative correlation of the low-energy structures of modelled gas-phase polypeptides, and their corresponding ECD dissociation pattern.

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

    PubMed

    Monro, Jean A; Puri, Basant K

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  2. Evaluation of neutron radiation field in carbon ion therapy

    NASA Astrophysics Data System (ADS)

    Xu, Jun-Kui; Su, You-Wu; Li, Wu-Yuan; Yan, Wei-Wei; Chen, Xi-Meng; Mao, Wang; Pang, Cheng-Guo

    2016-01-01

    Carbon ions have significant advantages in tumor therapy because of their physical and biological properties. In view of the radiation protection, the safety of patients is the most important issue in therapy processes. Therefore, the effects of the secondary particles produced by the carbon ions in the tumor therapy should be carefully considered, especially for the neutrons. In the present work, the neutron radiation field induced by carbon ions was evaluated by using the FLUKA code. The simulated results of neutron energy spectra and neutron dose was found to be in good agreement with the experiment data. In addition, energy deposition of carbon ions and neutrons in tissue-like media was studied, it is found that the secondary neutron energy deposition is not expected to exceed 1% of the carbon ion energy deposition in a typical treatment.

  3. Response of rat skin to boron neutron capture therapy with p-boronophenylalanine or borocaptate sodium.

    PubMed

    Morris, G M; Coderre, J A; Hopewell, J W; Micca, P L; Rezvani, M

    1994-08-01

    The effects of boron neutron capture irradiation employing either BPA or BSH as neutron capture agents has been assessed using the dorsal skin of Fischer 344 rats. Pharmacokinetic studies, using prompt gamma spectrometry, revealed comparable levels of boron-10 (10B) in blood and skin after the intravenous infusion of BSH (100 mg/kg body wt.). The 10B content of blood (12.0 +/- 0.5 micrograms/g) was slightly higher than that of skin (10.0 +/- 0.5 micrograms/g) after oral dosing with BPA. Biphasic skin reactions were observed after irradiation with the thermal neutron beam alone or in combination with BPA or BSH. The time of onset of the first phase of the skin reaction, moist desquamation, was approximately 2 weeks. The time at which the second-wave skin reaction, dermal necrosis, became evident was dose-related and occurred after a latent interval of > or = 24 weeks, well after the acute epithelial reaction had healed. The incidence of both phases of skin damage was also dose-related. The radiation doses required to produce skin damage in 50% of skin sites (ED50 values) were calculated from dose-effect curves and these values were used to determine relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors for both moist desquamation and dermal necrosis. It was concluded on the basis of these calculations that the microdistribution of the two neutron capture agents had a critical bearing on the overall biological effect after thermal neutron activation. BSH, which was possibly excluded from the cytoplasm of epidermal cells, had a low CBE factor value (0.56 +/- 0.06) while BPA, which may be selectively accumulated in epidermal cells had a very high CBE factor (3.74 +/- 0.7). For the dermal reaction, where vascular endothelial cells represent the likely target cell population, the CBE factor values were comparable, at 0.73 +/- 0.42 and 0.86 +/- 0.08 for BPA ad BSH, respectively.

  4. Conceptual design of an RFQ accelerator-based neutron source for boron neutron-capture therapy

    SciTech Connect

    Wangler, T.P.; Stovall, J.E.; Bhatia, T.S.; Wang, C.K.; Blue, T.E.; Gahbauer, R.A.

    1989-01-01

    We present a conceptual design of a low-energy neutron generator for treatment of brain tumors by boron neutron capture theory (BNCT). The concept is based on a 2.5-MeV proton beam from a radio-frequency quadrupole (RFQ) linac, and the neutrons are produced by the /sup 7/Li(p,n)/sup 7/Be reaction. A liquid lithium target and modulator assembly are designed to provide a high flux of epithermal neutrons. The patient is administered a tumor-specific /sup 10/Be-enriched compound and is irradiated by the neutrons to create a highly localized dose from the reaction /sup 10/B(n,..cap alpha..)/sup 7/Li. An RFQ accelerator-based neutron source for BNCT is compact, which makes it practical to site the facility within a hospital. 11 refs., 5 figs., 1 tab.

  5. 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.

  6. Computational characterization and experimental validation of the thermal neutron source for neutron capture therapy research at the University of Missouri

    SciTech Connect

    Broekman, J. D.; Nigg, D. W.; Hawthorne, M. F.

    2013-07-01

    Parameter studies, design calculations and neutronic performance measurements have been completed for a new thermal neutron beamline constructed 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. Validation protocols based on neutron activation spectrometry measurements and rigorous least-square adjustment techniques show that the beam produces a neutron spectrum that has the anticipated level of thermal neutron flux and a somewhat higher than expected, but radio-biologically insignificant, epithermal neutron flux component. (authors)

  7. 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.

  8. Functionalization and cellular uptake of boron carbide nanoparticles. The first step toward T cell-guided boron neutron capture therapy.

    PubMed

    Mortensen, M W; Björkdahl, O; Sørensen, P G; Hansen, T; Jensen, M R; Gundersen, H J G; Bjørnholm, T

    2006-01-01

    In this paper we present surface modification strategies of boron carbide nanoparticles, which allow for bioconjugation of the transacting transcriptional activator (TAT) peptide and fluorescent dyes. Coated nanoparticles can be translocated into murine EL4 thymoma cells and B16 F10 malignant melanoma cells in amounts as high as 0.3 wt. % and 1 wt. %, respectively. Neutron irradiation of a test system consisting of untreated B16 cells mixed with B16 cells loaded with boron carbide nanoparticles were found to inhibit the proliferative capacity of untreated cells, showing that cells loaded with boron-containing nanoparticles can hinder the growth of neighboring cells upon neutron irradiation. This could provide the first step toward a T cell-guided boron neutron capture therapy.

  9. 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.

  10. OPTIMIZATION OF THE EPITHERMAL NEUTRON BEAM FOR BORON NEUTRON CAPTURE THERAPY AT THE BROOKHAVEN MEDICAL RESEARCH REACTOR.

    SciTech Connect

    HU,J.P.; RORER,D.C.; RECINIELLO,R.N.; HOLDEN,N.E.

    2002-08-18

    Clinical trials of Boron Neutron Capture Therapy for patients with malignant brain tumor had been carried out for half a decade, using an epithermal neutron beam at the Brookhaven's Medical Reactor. The decision to permanently close this reactor in 2000 cut short the efforts to implement a new conceptual design to optimize this beam in preparation for use with possible new protocols. Details of the conceptual design to produce a higher intensity, more forward-directed neutron beam with less contamination from gamma rays, fast and thermal neutrons are presented here for their potential applicability to other reactor facilities. Monte Carlo calculations were used to predict the flux and absorbed dose produced by the proposed design. The results were benchmarked by the dose rate and flux measurements taken at the facility then in use.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

    PubMed Central

    2013-01-01

    Background Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. Methods The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. Results The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Conclusions Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma. PMID:23915425

  17. From radiation-induced chromosome damage to cell death: modelling basic mechanisms and applications to boron neutron capture therapy.

    PubMed

    Ballarini, F; Bortolussi, S; Clerici, A M; Ferrari, C; Protti, N; Altieri, S

    2011-02-01

    Cell death is a crucial endpoint in radiation-induced biological damage: on one side, cell death is a reference endpoint to characterise the action of radiation in biological targets; on the other side, any cancer therapy aims to kill tumour cells. Starting from Lea's target theory, many models have been proposed to interpret radiation-induced cell killing; after briefly discussing some of these models, in this paper, a mechanistic approach based on an experimentally observed link between chromosome aberrations and cell death was presented. More specifically, a model and a Monte Carlo code originally developed for chromosome aberrations were extended to simulate radiation-induced cell death applying an experimentally observed one-to-one relationship between the average number of 'lethal aberrations' (dicentrics, rings and deletions) per cell and -ln S, S being the fraction of surviving cells. Although such observation was related to X rays, in the present work, the approach was also applied to protons and alpha particles. A good agreement between simulation outcomes and literature data provided a model validation for different radiation types. The same approach was then successfully applied to simulate the survival of cells enriched with boron and irradiated with thermal neutrons at the Triga Mark II reactor in Pavia, to mimic a typical treatment for boron neutron capture therapy. PMID:21159746

  18. 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

  19. Tune-stabilized linear-field FFAG for carbon therapy

    SciTech Connect

    Johnstone, C.; Koscielniak, S.; /TRIUMF

    2006-07-01

    A hybrid design for a Fixed-Field Alternating-Gradient (FFAG) accelerator has been invented which uses edge and alternating-gradient focusing principles applied in a specific configuration to a combined-function magnet to stabilize tunes through an acceleration cycle which extends over a factor of 2-6 in momentum. Using normal conducting magnets, the final, extracted energy from this machine attains 400 MeV/nucleon and thus supports a carbon ion beam in the energy range of interest for cancer therapy. Competing machines for this application include superconducting cyclotrons[1], synchrotrons[2], and, more recently, scaling FFAGs. The machine proposed here has the high average current advantage of the cyclotron with smaller radial aperture requirements that are more typical of the synchrotron; and as such represents a desirable innovation for therapy machines.

  20. Shaping magnetic fields to direct therapy to ears and eyes.

    PubMed

    Shapiro, B; Kulkarni, S; Nacev, A; Sarwar, A; Preciado, D; Depireux, D A

    2014-07-11

    Magnetic fields have the potential to noninvasively direct and focus therapy to disease targets. External magnets can apply forces on drug-coated magnetic nanoparticles, or on living cells that contain particles, and can be used to manipulate them in vivo. Significant progress has been made in developing and testing safe and therapeutic magnetic constructs that can be manipulated by magnetic fields. However, we do not yet have the magnet systems that can then direct those constructs to the right places, in vivo, over human patient distances. We do not yet know where to put the external magnets, how to shape them, or when to turn them on and off to direct particles or magnetized cells-in blood, through tissue, and across barriers-to disease locations. In this article, we consider ear and eye disease targets. Ear and eye targets are too deep and complex to be targeted by a single external magnet, but they are shallow enough that a combination of magnets may be able to direct therapy to them. We focus on how magnetic fields should be shaped (in space and time) to direct magnetic constructs to ear and eye targets.

  1. Application of shock capturing and characteristics methods to shuttle flow fields

    NASA Technical Reports Server (NTRS)

    Kutler, P.; Rakich, J. V.; Mateer, G. G.

    1972-01-01

    The calculation of real gas flows around the space shuttle vehicle can be accomplished by the method of characteristics (MOC) or shock capture technique (SCT). Results obtained with these methods for an early orbiter shape proposed by the North American Rockwell Corporation and also for the more recent 040A configuration suggested by NASA-MSC are presented. Results obtained with the SCT code demonstrate its three-dimensional, multiple shock capturing capability while results obtained with the MOC code demonstrate the calculation of equilibrium real gas flows and the determination of flow variables required for a heating analysis.

  2. Biomedical irradiation system for boron neutron capture therapy at the Kyoto University Reactor.

    PubMed

    Kobayashi, T; Kanda, K; Ujeno, Y; Ishida, M R

    1990-01-01

    Physics studies related to radiation source, spectroscopy, beam quality, dosimetry, and biomedical applications using the Kyoto University Reactor Heavy Water Facility are described. Also, described are a Nickel Mirror Neutron Guide Tube and a Super Mirror Neutron Guide Tube that are used both for the measurement of boron concentration in phantom and living tissue and for precise measurements of neutron flux in phantom in the presence of both light and heavy water. Discussed are: (1) spectrum measurements using the time of flight technique, (2) the elimination of gamma rays and fast neutrons from a thermal neutron irradiation field, (3) neutron collimation without producing secondary gamma rays, (4) precise neutron flux measurements, dose estimation, and the measurement of boron concentration in tumor and its periphery using guide tubes, (5) the dose estimation of boron-10 for the first melanoma patient, and (6) special-purpose biological irradiation equipment. Other related subjects are also described.

  3. Electrostatic design and beam transport for a folded tandem electrostatic quadrupole accelerator facility for accelerator-based boron neutron capture therapy.

    PubMed

    Vento, V Thatar; Bergueiro, J; Cartelli, D; Valda, A A; Kreiner, A J

    2011-12-01

    Within the frame of an ongoing project to develop a folded Tandem-Electrostatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT), we discuss here the electrostatic design of the machine, including the accelerator tubes with electrostatic quadrupoles and the simulations for the transport and acceleration of a high intensity beam.

  4. An exact and efficient 3D reconstruction method from captured light-fields using the fractional Fourier transform

    NASA Astrophysics Data System (ADS)

    Mhabary, Ziv; Levi, Ofer; Small, Eran; Stern, Adrian

    2016-06-01

    Recently we have introduced a new method for refocusing images from captured light fields. The method is based on the fractional Fourier transform and allows refocusing a stack of images with a single step. The new techniques is computational efficient and more exact than alternative ones as it doesn't need any interpolations. Here we overview the method present a comparison of our technique to other refocusing techniques.

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

    SciTech Connect

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

    2014-11-01

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

  6. What is the role of field-directed therapy in the treatment of actinic keratosis? Part 2: Commonly used field-directed and lesion-directed therapies.

    PubMed

    Berman, Brian; Cohen, David E; Amini, Sadegh

    2012-06-01

    Actinic keratosis (AK) constitutes the initial epidermal lesion in a disease continuum that may potentially progress to invasive squamous cell carcinoma (SCC). A number of treatment options are available to clear lesions and thus reduce the risk for progression to SCC. Field-directed therapies are primarily used to clear multiple AKs and subclinical lesions. Part 1 of this review explaining the role of field-directed therapy for the treatment of AK discussed the unmet needs with current therapies and the investigational agents that are being developed to fill treatment gaps. Part 2 will mainly focus on field-directed therapies that currently are available for AK, such as resurfacing procedures, patient-administered topical therapy, and photodynamic therapy (PDT), as well as lesion-directed therapy, which is used to clear discrete lesions in relatively small numbers. PMID:22838095

  7. Delivery of (10)boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy.

    PubMed

    Obayashi, Shigeki; Kato, Itsuro; Ono, Koji; Masunaga, Shin-Ichiro; Suzuki, Minoru; Nagata, Kenji; Sakurai, Yoshinori; Yura, Yoshiaki

    2004-05-01

    Boron neutron capture therapy (BNCT) is a unique radiation therapy in which boron compounds are trapped into tumor cells. To determine the biodistribution of boronophenylalanine (BPA) in nude mice carrying oral squamous cell carcinoma (SCC), BPA was administered at a dose of 250 mg/kg body weight intraperitoneally. Two hours later, (10)B concentration in the tumor was 15.96 ppm and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 6.44, 4.19, 4.68 and 4.56, respectively. Two hours after the administration of borocaptate sodium (BSH) at a dose of 75 mg/kg body weight, (10)B concentration in the tumor was 3.61 ppm, and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 0.77, 1.05, 0.60 and 0.59, respectively. When cultured oral SCC cells were incubated with BPA or BSH for 2 h and then exposed to thermal neutrons, the proportion of survival cells that were capable of forming cell colonies decreased exponentially, depending on (10)B concentration. BPA-mediated BNCT was more efficient than BSH-mediated BNCT. Addition of boron compounds in the cell suspension during neutron irradiation enhanced the cell-killing effect of the neutrons. These results indicate that BPA is more selectively incorporated into human oral SCC as compared with normal oral tissues, and that both extra- and intra-cellular BPA contribute to the cell-killing effect of BNCT. BPA may be a useful boron carrier for BNCT in the treatment of advanced oral SCC.

  8. Localized electric field of plasmonic nanoplatform enhanced photodynamic tumor therapy.

    PubMed

    Li, Yiye; Wen, Tao; Zhao, Ruifang; Liu, Xixi; Ji, Tianjiao; Wang, Hai; Shi, Xiaowei; Shi, Jian; Wei, Jingyan; Zhao, Yuliang; Wu, Xiaochun; Nie, Guangjun

    2014-11-25

    Near-infrared plasmonic nanoparticles demonstrate great potential in disease theranostic applications. Herein a nanoplatform, composed of mesoporous silica-coated gold nanorods (AuNRs), is tailor-designed to optimize the photodynamic therapy (PDT) for tumor based on the plasmonic effect. The surface plasmon resonance of AuNRs was fine-tuned to overlap with the exciton absorption of indocyanine green (ICG), a near-infrared photodynamic dye with poor photostability and low quantum yield. Such overlap greatly increases the singlet oxygen yield of incorporated ICG by maximizing the local field enhancement, and protecting the ICG molecules against photodegradation by virtue of the high absorption cross section of the AuNRs. The silica shell strongly increased ICG payload with the additional benefit of enhancing ICG photostability by facilitating the formation of ICG aggregates. As-fabricated AuNR@SiO2-ICG nanoplatform enables trimodal imaging, near-infrared fluorescence from ICG, and two-photon luminescence/photoacoustic tomography from the AuNRs. The integrated strategy significantly improved photodynamic destruction of breast tumor cells and inhibited the growth of orthotopic breast tumors in mice, with mild laser irradiation, through a synergistic effect of PDT and photothermal therapy. Our study highlights the effect of local field enhancement in PDT and demonstrates the importance of systematic design of nanoplatform to greatly enhancing the antitumor efficacy. PMID:25375193

  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. Designing power supplies for 2.5 MV, 100 mADC for Boron Neutron Capture Therapy

    NASA Astrophysics Data System (ADS)

    Reginato, L. L.; Ayers, J.; Johnson, R.; Peters, C.; Stevenson, R.

    1997-02-01

    Renewed interest by several major university medical centers (UCSF, Stanford, U. of Washington, Loma Linda) in conducting Boron Neutron Capture Therapy (BNCT) led to the investigation of generating a continuous proton beam with 2.5 MeV of energy and up to 100 mA of current. The power supply for the Heavy Ion Injector (Adam) at LBNL operated at lower currents from its completion in 1970 until it was shut down in 1993. This power supply consisted of 64 stages of shunt-fed multipliers (Dynamitron) and seemed to offer an attractive first step for BNCT experiments. The Adam power supply was reactivated in June of 1995 and extensive tests were performed to establish its maximum capability. After the tests were completed, it became clear that 100 mA was well beyond the capability of this power source and that even 10-20 mA would require extensive modifications. After some initial conceptual design studies, it was decided that the air-coupled transformer with multiple secondaries warranted some serious investigations and could offer the best chance for achieving 100 mA.

  11. Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part II.

    PubMed

    Imahori, Y; Ueda, S; Ohmori, Y; Sakae, K; Kusuki, T; Kobayashi, T; Takagaki, M; Ono, K; Ido, T; Fujii, R

    1998-08-01

    Based on pharmacokinetic findings of fluorine-18-labeled L-fluoroboronophenylalanine by positron emission tomography (PET), methods for estimating tumor 10B concentration were devised. In clinical practice of boron neutron capture therapy (BNCT) for high-grade gliomas, a large amount of L-boronophenylalanine (L-10B-BPA)-fructose solution is used. Under these conditions, a slow i.v. infusion of L-10B-BPA-fructose solution should be performed for BNCT; therefore, the changes over time in 10B concentration in the target tissue were estimated by convoluting the actual time course of changes in plasma 10B concentration with a PET-based weight function including the proper rate constants [K1 (ml/g/min), k2 (min(-1)), k3 (min(-1)), and k4 (min(-1))]. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This demonstrated the similarity in pharmacokinetics between fluorine-18-labeled L-fluoroboronophenylalanine and L-10B-BPA. This method, using the appropriate rate constant, permits the determination of tumor 10B concentration and is widely suitable for clinical BNCT, because the averaged PET data are enough to use in future patients without individual PET study.

  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. Improved treatment planning for boron neutron capture therapy for glioblastoma multiforme using fluorine-18 labeled boronophenylalanine and positron emission tomography.

    PubMed

    Nichols, Trent L; Kabalka, George W; Miller, Laurence F; Khan, Mohammad K; Smith, Gary T

    2002-10-01

    Boron neutron capture therapy (BNCT) is a cancer brachytherapy based upon the thermal neutron reaction: 10B(n,alpha)7Li. The efficacy of the treatment depends primarily upon two conditions being met: (a) the preferential concentration of a boronated compound in the neoplasm and (b) an adequate fluence of thermal neutrons delivered to the neoplasm. The boronated amino acid, para-boronophenylalanine (BPA), is the agent widely used in clinical trials to deliver 10B to the malignancy. Positron emission tomography (PET) can be used to generate in vivo boron distribution maps by labeling BPA with the positron emitting nuclide fluorine-18. The incorporation of the PET-derived boron distribution maps into current treatment planning protocols is shown to provide improved treatment plans. Using previously established protocols, six patients with glioblastoma had 18BPA PET scans. The PET distribution maps obtained were used in the conventional BNCT treatment codes. The isodose curves derived from the PET data are shown to differ both qualitatively and quantitatively from the conventional isodose curves that were derived from calculations based upon the assumption of uniform uptake of the pharmaceutical in tumor and normal brain regions. The clinical course of each of the patients who eventually received BNCT (five of the six patients) was compared using both sets of isodose calculations. The isodose contours based upon PET derived distribution data appear to be more consistent with the patients' clinical course. PMID:12408309

  14. 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

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

    PubMed

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

    2011-04-01

    Boron neutron capture therapy (BNCT) is a binary radiotherapy based on thermal-neutron irradiation of cells enriched with (10)B, which produces α particles and (7)Li ions of short range and high biological effectiveness. The selective uptake of boron by tumor cells is a crucial issue for BNCT, and studies of boron uptake and washout associated with cell survival studies can be of great help in developing clinical applications. In this work, boron uptake and washout were characterized both in vitro for the DHDK12TRb (DHD) rat colon carcinoma cell line and in vivo using rats bearing liver metastases from DHD cells. Despite a remarkable uptake, a large boron release was observed after removal of the boron-enriched medium from in vitro cell cultures. However, analysis of boron washout after rat liver perfusion in vivo did not show a significant boron release, suggesting that organ perfusion does not limit the therapeutic effectiveness of the treatment. The survival of boron-loaded cells exposed to thermal neutrons was also assessed; the results indicated that the removal of extracellular boron does not limit treatment effectiveness if adequate amounts of boron are delivered and if the cells are kept at low temperature. Cell survival was also investigated theoretically using a mechanistic model/Monte Carlo code originally developed for radiation-induced chromosome aberrations and extended here to cell death; good agreement between simulation outcomes and experimental data was obtained. PMID:21133762

  16. 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

  17. Synthesis, characterization and biological evaluation of carboranylmethylbenzo[b]acridones as novel agents for boron neutron capture therapy.

    PubMed

    da Silva, A Filipa F; Seixas, Raquel S G R; Silva, Artur M S; Coimbra, Joana; Fernandes, Ana C; Santos, Joana P; Matos, António; Rino, José; Santos, Isabel; Marques, Fernanda

    2014-07-28

    Herein we present the synthesis and characterization of benzo[b]acridin-12(7H)-ones bearing carboranyl moieties and test their biological effectiveness as boron neutron capture therapy (BNCT) agents in cancer treatment. The cellular uptake of these novel compounds into the U87 human glioblastoma cells was evaluated by boron analysis (ICP-MS) and by fluorescence imaging (confocal microscopy). The compounds enter the U87 cells exhibiting a similar profile, i.e., preferential accumulation in the cytoskeleton and membranes and a low cytotoxic activity (IC50 values higher than 200 μM). The cytotoxic activity and cellular morphological alterations after neutron irradiation in the Portuguese Research Reactor (6.6 × 10(7) neutrons cm(-2) s(-1), 1 MW) were evaluated by the MTT assay and by electron microscopy (TEM). Post-neutron irradiation revealed that BNCT has a higher cytotoxic effect on the cells. Accumulation of membranous whorls in the cytoplasm of cells treated with one of the compounds correlates well with the cytotoxic effect induced by radiation. Results provide a strong rationale for considering one of these compounds as a lead candidate for a new generation of BNCT agents.

  18. 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

  19. Design of neutron beams at the Argonne Continuous Wave Linac (ACWL) for boron neutron capture therapy and neutron radiography

    SciTech Connect

    Zhou, X.L.; McMichael, G.E.

    1994-10-01

    Neutron beams are designed for capture therapy based on p-Li and p-Sc reactions using the Argonne Continuous Wave Linac (ACWL). The p-Li beam will provide a 2.5 {times} 10{sup 9} n/cm{sup 2}s epithermal flux with 7 {times} 10{sup 5} {gamma}/cm{sup 2}s contamination. On a human brain phantom, this beam allows an advantage depth (AD) of 10 cm, an advantage depth dose rate (ADDR) of 78 cGy/min and an advantage ratio (AR) of 3.2. The p-Sc beam offers 5.9 {times} 10{sup 7} n/cm{sup 2}s and a dose performance of AD = 8 cm and AR = 3.5, suggesting the potential of near-threshold (p,n) reactions such as the p-Li reaction at E{sub p} = 1.92 MeV. A thermal radiography beam could also be obtained from ACWL.

  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. Angular distribution of characteristic photons after radiative electron capture at strong central fields

    SciTech Connect

    Drukarev, E. G.; Ma, X.; Mikhailov, A. I.; Mikhailov, I. A.; Mokler, P. H.

    2006-08-15

    We investigate the difference in the angular distribution of Ly-{alpha}{sub 1} and K{alpha}{sub 1} photons from hydrogenlike and heliumlike ions of uranium after radiative electron capture to the L shell. The strong anisotropy in the former case is changed to a very small one in the latter case. Our calculations support the observation. The effect takes place even in the limiting case of noninteracting electrons, being caused by the Pauli principle.

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

    USGS Publications Warehouse

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

    1990-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  4. Relative biological effectiveness (RBE) of thermal neutron capture therapy of cultured B-16 melanoma cells preincubated with 10B-paraboronophenylalanine.

    PubMed

    Ichihashi, M; Sasase, A; Hiramoto, T; Funasaka, Y; Hatta, S; Mishima, Y; Kobayashi, T; Fukuda, H; Yoshino, K

    1989-01-01

    An experimental study of the relative biological effectiveness (RBE) of thermal neutron capture therapy (TNCT) for melanoma cell inactivation using 10B1-paraboronophenylalanine (10B1-BPA) was carried out to demonstrate a high therapeutic effect of TNCT, compared with that of fast neutron. Cells preincubated with or without 10B1-BPA at a concentration of 50 micrograms/ml for 20 h were irradiated with 60Co gamma-ray, fast neutron or thermal neutron. The absorbed dose of the cells from thermal neutron was calculated by Kobayashi's model. The D0 value of fast neutron was 1.07 Gy, and the D0S of thermal neutron radiation with or without preincubation of the cells with 10B1-BPA were 0.46 Gy or 0.67 Gy, respectively. The RBEs of fast neutron, thermal neutron beams, and neutron capture therapy relative to 60Co gamma-ray were calculated as 2.78, 4.18, and 6.15 at 0.1 surviving fraction, respectively. These results indicate radiologically that thermal neutron capture therapy using 10B1-BPA is an excellent radiation therapy for malignant melanoma.

  5. 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

  6. 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

  7. Selectivity and limitations of carbon sorption tubes for capturing siloxanes in biogas during field sampling.

    PubMed

    Tansel, Berrin; Surita, Sharon C

    2016-06-01

    Siloxane levels in biogas can jeopardize the warranties of the engines used at the biogas to energy facilities. The chemical structure of siloxanes consists of silicon and oxygen atoms, alternating in position, with hydrocarbon groups attached to the silicon side chain. Siloxanes can be either in cyclic (D) or linear (L) configuration and referred with a letter corresponding to their structure followed by a number corresponding to the number of silicon atoms present. When siloxanes are burned, the hydrocarbon fraction is lost and silicon is converted to silicates. The purpose of this study was to evaluate the adequacy of activated carbon gas samplers for quantitative analysis of siloxanes in biogas samples. Biogas samples were collected from a landfill and an anaerobic digester using multiple carbon sorbent tubes assembled in series. One set of samples was collected for 30min (sampling 6-L gas), and the second set was collected for 60min (sampling 12-L gas). Carbon particles were thermally desorbed and analyzed by Gas Chromatography Mass Spectrometry (GC/MS). The results showed that biogas sampling using a single tube would not adequately capture octamethyltrisiloxane (L3), hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6). Even with 4 tubes were used in series, D5 was not captured effectively. The single sorbent tube sampling method was adequate only for capturing trimethylsilanol (TMS) and hexamethyldisiloxane (L2). Affinity of siloxanes for activated carbon decreased with increasing molecular weight. Using multiple carbon sorbent tubes in series can be an appropriate method for developing a standard procedure for determining siloxane levels for low molecular weight siloxanes (up to D3). Appropriate quality assurance and quality control procedures should be developed for adequately quantifying the levels of the higher molecular weight siloxanes in biogas with sorbent tubes.

  8. Selectivity and limitations of carbon sorption tubes for capturing siloxanes in biogas during field sampling.

    PubMed

    Tansel, Berrin; Surita, Sharon C

    2016-06-01

    Siloxane levels in biogas can jeopardize the warranties of the engines used at the biogas to energy facilities. The chemical structure of siloxanes consists of silicon and oxygen atoms, alternating in position, with hydrocarbon groups attached to the silicon side chain. Siloxanes can be either in cyclic (D) or linear (L) configuration and referred with a letter corresponding to their structure followed by a number corresponding to the number of silicon atoms present. When siloxanes are burned, the hydrocarbon fraction is lost and silicon is converted to silicates. The purpose of this study was to evaluate the adequacy of activated carbon gas samplers for quantitative analysis of siloxanes in biogas samples. Biogas samples were collected from a landfill and an anaerobic digester using multiple carbon sorbent tubes assembled in series. One set of samples was collected for 30min (sampling 6-L gas), and the second set was collected for 60min (sampling 12-L gas). Carbon particles were thermally desorbed and analyzed by Gas Chromatography Mass Spectrometry (GC/MS). The results showed that biogas sampling using a single tube would not adequately capture octamethyltrisiloxane (L3), hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6). Even with 4 tubes were used in series, D5 was not captured effectively. The single sorbent tube sampling method was adequate only for capturing trimethylsilanol (TMS) and hexamethyldisiloxane (L2). Affinity of siloxanes for activated carbon decreased with increasing molecular weight. Using multiple carbon sorbent tubes in series can be an appropriate method for developing a standard procedure for determining siloxane levels for low molecular weight siloxanes (up to D3). Appropriate quality assurance and quality control procedures should be developed for adequately quantifying the levels of the higher molecular weight siloxanes in biogas with sorbent tubes

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

    NASA Astrophysics Data System (ADS)

    Sztejnberg Goncalves-Carralves, Manuel Leonardo

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

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

    SciTech Connect

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

    2012-06-21

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

  11. Boron neutron capture therapy (BNCT) for the treatment of spontaneous nasal planum squamous cell carcinoma in felines.

    PubMed

    Trivillin, Verónica A; Heber, Elisa M; Rao, Monica; Cantarelli, María A; Itoiz, Maria E; Nigg, David W; Calzetta, Osvaldo; Blaumann, Herman; Longhino, Juan; Schwint, Amanda E

    2008-02-01

    Recently, Boron neutron capture therapy (BNCT) was successfully applied to treat experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa, with no damage to normal tissue. It was also shown that treating spontaneous nasal planum SCC in terminal feline patients with low dose BNCT is safe and feasible. In an extension of this work, the present study aimed at evaluation of the response of tumor and dose-limiting normal tissues to potentially therapeutic BNCT doses. Biodistribution studies with (10)B-boronophenylalanine (BPA enriched in (10)B) as a (10)B carrier were performed on three felines that showed advanced nasal planum SCC without any standard therapeutic option. Following the biodistribution studies, BNCT mediated by (10)BPA was done using the thermalized epithermal neutron beam at the RA-6 Nuclear Reactor. Follow-up included clinical evaluation, assessment of macroscopic tumor and normal tissue response and biopsies for histopathological analysis. The treated animals did not show any apparent radiation-induced toxicity. All three animals exhibited partial tumor control and an improvement in clinical condition. Enhanced therapeutic efficacy was associated with a high (10)B content of the tumor and a small tumor size. BNCT is therefore believed to be potentially effective in the treatment of spontaneous SCC. However, improvement in targeting (10)B into all tumor cells and delivering a sufficient dose at a greater depth are still required for the treatment of deep-seated, large tumors. Future studies are needed to evaluate the potential efficacy of the dual mode cellular (e.g. BPA-BNCT) and vascular (e.g. GB-10-BNCT) targeting protocol in a preclinical scenario, employing combinations of (10)B compounds with different properties and complementary uptake mechanisms. PMID:17955256

  12. Boron self-shielding effects on dose delivery of neutron capture therapy using epithermal beam and boronophenylalanine.

    PubMed

    Ye, S J

    1999-11-01

    Previous dosimetry studies for boron neutron capture therapy have often neglected the thermal neutron self-shielding effects caused by the 10B accumulation in the brain and the tumor. The neglect of thermal neutron flux depression, therefore, results in an overestimation of the actual dose delivery. The relevant errors are expected to be more pronounced when boronophenylalanine is used in conjunction with an epithermal neutron beam. In this paper, the boron self-shielding effects are calculated in terms of the thermal neutron flux depression across the brain and the dose delivered to the tumors. The degree of boron self-shielding is indicated by the difference between the thermal neutron fluxes calculated with and without considering a 10B concentration as part of the head phantom composition. The boron self-shielding effect is found to increase with increasing 10B concentrations and penetration depths from the skin. The calculated differences for 10B concentrations of 7.5-30 ppm are 2.3%-8.3% at 2.3 cm depth (depth of the maximum brain dose) and 4.6%-17% at 7.3 cm depth (the center of the brain). The additional self-shielding effects by the 10B concentration in a bulky tumor are investigated for a 3-cm-diam spherical tumor located either near the surface (3.3 cm depth) or at the center of the brain (7.3 cm depth) along the beam centerline. For 45 ppm of 10B in the tumor and 15 ppm of 10B in the brain, the dose delivered to the tumors is approximately 10% lower at 3.3 cm depth and 20% lower at the center of the brain, compared to the dose neglecting the boron self-shielding in transport calculations.

  13. 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.

  14. Characteristics comparison between a cyclotron-based neutron source and KUR-HWNIF for boron neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Tanaka, H.; Sakurai, Y.; Suzuki, M.; Masunaga, S.; Kinashi, Y.; Kashino, G.; Liu, Y.; Mitsumoto, T.; Yajima, S.; Tsutsui, H.; Maruhashi, A.; Ono, K.

    2009-06-01

    At Kyoto University Research Reactor Institute (KURRI), 275 clinical trials of boron neutron capture therapy (BNCT) have been performed as of March 2006, and the effectiveness of BNCT has been revealed. In order to further develop BNCT, it is desirable to supply accelerator-based epithermal-neutron sources that can be installed near the hospital. We proposed the method of filtering and moderating fast neutrons, which are emitted from the reaction between a beryllium target and 30-MeV protons accelerated by a cyclotron accelerator, using an optimum moderator system composed of iron, lead, aluminum and calcium fluoride. At present, an epithermal-neutron source is under construction from June 2008. This system consists of a cyclotron accelerator, beam transport system, neutron-yielding target, filter, moderator and irradiation bed. In this article, an overview of this system and the properties of the treatment neutron beam optimized by the MCNPX Monte Carlo neutron transport code are presented. The distribution of biological effect weighted dose in a head phantom compared with that of Kyoto University Research Reactor (KUR) is shown. It is confirmed that for the accelerator, the biological effect weighted dose for a deeply situated tumor in the phantom is 18% larger than that for KUR, when the limit dose of the normal brain is 10 Gy-eq. The therapeutic time of the cyclotron-based neutron sources are nearly one-quarter of that of KUR. The cyclotron-based epithermal-neutron source is a promising alternative to reactor-based neutron sources for treatments by BNCT.

  15. 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.

  16. 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.

  17. 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.

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

    SciTech Connect

    Burns, T.D. Jr.

    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 {times} 10{sup 8} n/cm{sup 2} {center_dot} s. The fast neutron and gamma radiation KERMA factors are 10 {times} 10{sup {minus}11}cGy{center_dot}cm{sup 2}/n{sub epi} and 20 {times} 10{sup {minus}11} cGy{center_dot}cm{sup 2}/n{sub epi}, 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. 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

  20. Dosimetry and radiobiology at the new RA-3 reactor boron neutron capture therapy (BNCT) facility: application to the treatment of experimental oral cancer.

    PubMed

    Pozzi, E; Nigg, D W; Miller, M; Thorp, S I; Heber, E M; Zarza, L; Estryk, G; Monti Hughes, A; Molinari, A J; Garabalino, M; Itoiz, M E; Aromando, R F; Quintana, J; Trivillin, V A; Schwint, A E

    2009-07-01

    The National Atomic Energy Commission of Argentina (CNEA) constructed a novel thermal neutron source for use in boron neutron capture therapy (BNCT) applications at the RA-3 research reactor facility located in Buenos Aires. The aim of the present study was to perform a dosimetric characterization of the facility and undertake radiobiological studies of BNCT in an experimental model of oral cancer in the hamster cheek pouch. The free-field thermal flux was 7.1 x 10(9) n cm(-2)s(-1) and the fast neutron flux was 2.5 x 10(6) n cm(-2)s(-1), indicating a very well-thermalized neutron field with negligible fast neutron dose. For radiobiological studies it was necessary to shield the body of the hamster from the neutron flux while exposing the everted cheek pouch bearing the tumors. To that end we developed a lithium (enriched to 95% in (6)Li) carbonate enclosure. Groups of tumor-bearing hamsters were submitted to BPA-BNCT, GB-10-BNCT, (GB-10+BPA)-BNCT or beam only treatments. Normal (non-cancerized) hamsters were treated similarly to evaluate normal tissue radiotoxicity. The total physical dose delivered to tumor with the BNCT treatments ranged from 6 to 8.5 Gy. Tumor control at 30 days ranged from 73% to 85%, with no normal tissue radiotoxicity. Significant but reversible mucositis in precancerous tissue surrounding tumors was associated to BPA-BNCT. The therapeutic success of different BNCT protocols in treating experimental oral cancer at this novel facility was unequivocally demonstrated. PMID:19380233

  1. Dosimetry and radiobiology at the new RA-3 reactor boron neutron capture therapy (BNCT) facility: application to the treatment of experimental oral cancer.

    PubMed

    Pozzi, E; Nigg, D W; Miller, M; Thorp, S I; Heber, E M; Zarza, L; Estryk, G; Monti Hughes, A; Molinari, A J; Garabalino, M; Itoiz, M E; Aromando, R F; Quintana, J; Trivillin, V A; Schwint, A E

    2009-07-01

    The National Atomic Energy Commission of Argentina (CNEA) constructed a novel thermal neutron source for use in boron neutron capture therapy (BNCT) applications at the RA-3 research reactor facility located in Buenos Aires. The aim of the present study was to perform a dosimetric characterization of the facility and undertake radiobiological studies of BNCT in an experimental model of oral cancer in the hamster cheek pouch. The free-field thermal flux was 7.1 x 10(9) n cm(-2)s(-1) and the fast neutron flux was 2.5 x 10(6) n cm(-2)s(-1), indicating a very well-thermalized neutron field with negligible fast neutron dose. For radiobiological studies it was necessary to shield the body of the hamster from the neutron flux while exposing the everted cheek pouch bearing the tumors. To that end we developed a lithium (enriched to 95% in (6)Li) carbonate enclosure. Groups of tumor-bearing hamsters were submitted to BPA-BNCT, GB-10-BNCT, (GB-10+BPA)-BNCT or beam only treatments. Normal (non-cancerized) hamsters were treated similarly to evaluate normal tissue radiotoxicity. The total physical dose delivered to tumor with the BNCT treatments ranged from 6 to 8.5 Gy. Tumor control at 30 days ranged from 73% to 85%, with no normal tissue radiotoxicity. Significant but reversible mucositis in precancerous tissue surrounding tumors was associated to BPA-BNCT. The therapeutic success of different BNCT protocols in treating experimental oral cancer at this novel facility was unequivocally demonstrated.

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

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  3. Intensity modulated arc therapy (IMAT) with centrally blocked rotational fields.

    PubMed

    Cotrutz, C; Kappas, C; Webb, S

    2000-08-01

    A new technique for intensity-modulated beam (IMB) delivery that combines the features of intensity modulated arc therapy (IMAT) with the use of 'classical blocks' is proposed. The role of the blocks is to realize the high-gradient modulation of the intensity profile corresponding to the region to be protected within the body contour, while the MLC leaves or the secondary collimator defines the rest of the field and delivers intensity-modulated multiple rotational segments. The centrally blocked radiation fields are applied sequentially, in several rotations. Each rotation of the gantry is responsible for delivering one segment of the optimal intensity profile. The new IMAT technique is applied for a treatment geometry represented by an annular target volume centrally located within a circular body contour. The annulus encompasses a circular critical structure, which is to be protected. The beam opening and corresponding weight of each segment are determined in two ways. The first method applies a linear optimization algorithm to precalculated centrally blocked radial dose profiles. These radial profiles are calculated for a set of beam openings, ranging from the largest field that covers the whole planning target volume (PTV) to the smallest, which is 1 cm larger than the width of the central block. The optimization is subjected to dose homogeneity constraints imposed on a linear combination of these profiles and finally delivers the dimensions and weights of the rotational beams to be used in combination. The second method decomposes into several subfields the fluence profile of a rotational beam known to deliver a constant dose level to PTV. This fluence profile is determined by using the analytical method proposed by Brahme for the case of the annular PTV and the concentric organ at risk (OAR). The proper segmentation of this intensity profile provides the field sizes and corresponding weights of the subfields to be used in combination. Both methods show that

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

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

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

  5. Degenerate mobilities in phase field models are insufficient to capture surface diffusion

    NASA Astrophysics Data System (ADS)

    Lee, Alpha A.; Münch, Andreas; Süli, Endre

    2015-08-01

    Phase field models frequently provide insight into phase transitions and are robust numerical tools to solve free boundary problems corresponding to the motion of interfaces. A body of prior literature suggests that interface motion via surface diffusion is the long-time, sharp interface limit of microscopic phase field models such as the Cahn-Hilliard equation with a degenerate mobility function. Contrary to this conventional wisdom, we show that the long-time behaviour of degenerate Cahn-Hilliard equation with a polynomial free energy undergoes coarsening, reflecting the presence of bulk diffusion, rather than pure surface diffusion. This reveals an important limitation of phase field models that are frequently used to model surface diffusion.

  6. Radiation injury of boron neutron capture therapy using mixed epithermal- and thermal neutron beams in patients with malignant glioma.

    PubMed

    Kageji, T; Nagahiro, S; Mizobuchi, Y; Toi, H; Nakagawa, Y; Kumada, H

    2004-11-01

    The purpose of this study was to clarify the radiation injury in acute or delayed stage after boron neutron capture therapy (BNCT) using mixed epithermal- and thermal neutron beams in patients with malignant glioma. Eighteen patients with malignant glioma underwent mixed epithermal- and thermal neutron beam and sodium borocaptate between 1998 and 2004. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the protocol used between 1998 and 2000 (Protocol A, n = 8) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B, n = 4); it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to 6 glioblastoma patients (Protocol C, n = 6). The average values of the maximum vascular dose of brain surface in Protocol A, B and C were 11.4+/-4.2 Gy, 15.7+/-1.2 and 13.9+/-3.6 Gy, respectively. Acute radiation injury such as a generalized convulsion within 1 week after BNCT was recognized in three patients of Protocol B. Delayed radiation injury such as a neurological deterioration appeared 3-6 months after BNCT, and it was recognized in 1 patient in Protocol A, 5 patients in Protocol B. According to acute radiation injury, the maximum vascular dose was 15.8+/-1.3 Gy in positive and was 12.6+/-4.3 Gy in negative. There was no significant difference between them. According to the delayed radiation injury, the maximum vascular dose was 13.8+/-3.8 Gy in positive and was 13.6+/-4.9 Gy in negative. There was no significant difference between them. The dose escalation is limited because most patients in Protocol B suffered from acute radiation injury. We conclude that the maximum vascular dose does not exceed over 12 Gy to avoid the delayed radiation injury, especially, it should be limited under 10 Gy in the case that tumor

  7. 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

  8. Acoustic and Cavitation Fields of Shock Wave Therapy Devices

    NASA Astrophysics Data System (ADS)

    Chitnis, Parag V.; Cleveland, Robin O.

    2006-05-01

    Extracorporeal shock wave therapy (ESWT) is considered a viable treatment modality for orthopedic ailments. Despite increasing clinical use, the mechanisms by which ESWT devices generate a therapeutic effect are not yet understood. The mechanistic differences in various devices and their efficacies might be dependent on their acoustic and cavitation outputs. We report acoustic and cavitation measurements of a number of different shock wave therapy devices. Two devices were electrohydraulic: one had a large reflector (HMT Ossatron) and the other was a hand-held source (HMT Evotron); the other device was a pneumatically driven device (EMS Swiss DolorClast Vet). Acoustic measurements were made using a fiber-optic probe hydrophone and a PVDF hydrophone. A dual passive cavitation detection system was used to monitor cavitation activity. Qualitative differences between these devices were also highlighted using a high-speed camera. We found that the Ossatron generated focused shock waves with a peak positive pressure around 40 MPa. The Evotron produced peak positive pressure around 20 MPa, however, its acoustic output appeared to be independent of the power setting of the device. The peak positive pressure from the DolorClast was about 5 MPa without a clear shock front. The DolorClast did not generate a focused acoustic field. Shadowgraph images show that the wave propagating from the DolorClast is planar and not focused in the vicinity of the hand-piece. All three devices produced measurable cavitation with a characteristic time (cavitation inception to bubble collapse) that varied between 95 and 209 μs for the Ossatron, between 59 and 283 μs for the Evotron, and between 195 and 431 μs for the DolorClast. The high-speed camera images show that the cavitation activity for the DolorClast is primarily restricted to the contact surface of the hand-piece. These data indicate that the devices studied here vary in acoustic and cavitation output, which may imply that the

  9. Optimization of inertial sensor-based motion capturing for magnetically distorted field applications.

    PubMed

    Schiefer, Christoph; Ellegast, Rolf P; Hermanns, Ingo; Kraus, Thomas; Ochsmann, Elke; Larue, Christian; Plamondon, André

    2014-12-01

    Inertial measurement units (IMU) are gaining increasing importance for human motion tracking in a large variety of applications. IMUs consist of gyroscopes, accelerometers, and magnetometers which provide angular rate, acceleration, and magnetic field information, respectively. In scenarios with a permanently distorted magnetic field, orientation estimation algorithms revert to using only angular rate and acceleration information. The result is an increasing drift error of the heading information. This article describes a method to compensate the orientation drift of IMUs using angular rate and acceleration readings in a quaternion-based algorithm. Zero points (ZP) were introduced, which provide additional heading and gyroscope bias information and were combined with bidirectional orientation computation. The necessary frequency of ZPs to achieve an acceptable error level is derived in this article. In a laboratory environment the method and the effect of varying interval length between ZPs was evaluated. Eight subjects were equipped with seven IMUs at trunk, head and upper extremities. They performed a predefined course of box handling for 40 min at different motion speeds and ranges of motion. The orientation estimation was compared to an optical motion tracking system. The resulting mean root mean squared error (RMSE) of all measurements ranged from 1.7 deg to 7.6 deg (roll and pitch) and from 3.5 deg to 15.0 deg (heading) depending on the measured segment, at a mean interval-length of 1.1 min between two ZPs without magnetometer usage. The 95% limits of agreement (LOA) ranged in best case from -2.9 deg to 3.6 deg at the hip roll angle and in worst case from -19.3 deg to 18.9 deg at the forearm heading angle. This study demonstrates that combining ZPs and bidirectional computation can reduce orientation error of IMUs in environments with magnetic field distortion.

  10. Optimization of inertial sensor-based motion capturing for magnetically distorted field applications.

    PubMed

    Schiefer, Christoph; Ellegast, Rolf P; Hermanns, Ingo; Kraus, Thomas; Ochsmann, Elke; Larue, Christian; Plamondon, André

    2014-12-01

    Inertial measurement units (IMU) are gaining increasing importance for human motion tracking in a large variety of applications. IMUs consist of gyroscopes, accelerometers, and magnetometers which provide angular rate, acceleration, and magnetic field information, respectively. In scenarios with a permanently distorted magnetic field, orientation estimation algorithms revert to using only angular rate and acceleration information. The result is an increasing drift error of the heading information. This article describes a method to compensate the orientation drift of IMUs using angular rate and acceleration readings in a quaternion-based algorithm. Zero points (ZP) were introduced, which provide additional heading and gyroscope bias information and were combined with bidirectional orientation computation. The necessary frequency of ZPs to achieve an acceptable error level is derived in this article. In a laboratory environment the method and the effect of varying interval length between ZPs was evaluated. Eight subjects were equipped with seven IMUs at trunk, head and upper extremities. They performed a predefined course of box handling for 40 min at different motion speeds and ranges of motion. The orientation estimation was compared to an optical motion tracking system. The resulting mean root mean squared error (RMSE) of all measurements ranged from 1.7 deg to 7.6 deg (roll and pitch) and from 3.5 deg to 15.0 deg (heading) depending on the measured segment, at a mean interval-length of 1.1 min between two ZPs without magnetometer usage. The 95% limits of agreement (LOA) ranged in best case from -2.9 deg to 3.6 deg at the hip roll angle and in worst case from -19.3 deg to 18.9 deg at the forearm heading angle. This study demonstrates that combining ZPs and bidirectional computation can reduce orientation error of IMUs in environments with magnetic field distortion. PMID:25321344

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

    PubMed Central

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

    2016-01-01

    Most fluorescence microscopes are inefficient, collecting only a small fraction of the emitted light at any instant. Besides wasting valuable signal, this inefficiency also reduces spatial resolution and causes imaging volumes to exhibit significant resolution anisotropy. We describe microscopic and computational techniques that address these problems by simultaneously capturing and subsequently fusing and deconvolving multiple specimen views. Unlike previous methods that serially capture multiple views, our approach improves spatial resolution without introducing any additional illumination dose or compromising temporal resolution relative to conventional imaging. When applying our methods to single-view wide-field or dual-view light-sheet microscopy, we achieve a twofold improvement in volumetric resolution (~235 nm × 235 nm × 340 nm) as demonstrated on a variety of samples including microtubules in Toxoplasma gondii, SpoVM in sporulating Bacillus subtilis, and multiple protein distributions and organelles in eukaryotic cells. In every case, spatial resolution is improved with no drawback by harnessing previously unused fluorescence. PMID:27761486

  12. Gas migration and carbon capture in one of the World's largest pockmark fields, the Norwegian Sea

    NASA Astrophysics Data System (ADS)

    Mazzini, A.; Svensen, H.; Planke, S.; Hammer, O.; Linge, H. C.; Forsberg, C. F.; Tjelta, T.

    2013-12-01

    Acoustic imaging has revealed more than 7000 pockmarks above the Troll East gas field in the Norwegian Sea. The pockmarks range in size from 10 to 100 meters in diameter and are typically 6 meters deep. High-resolution bathymetric data shows that there is no evidence of structural control on the location of the pockmarks. This conclusion is in agreement with statistical analysis of the pockmark distribution which shows neighbor avoidance up to a scale of hundreds of meters and no indication of a fractal geometry. The pockmarks generally represent isolated structures and sometimes are identified in clusters with a central parent pockmark surrounded by smaller sized satellite pockmarks. Seafloor observations show that carbonate deposits are common within the pockmarks, providing shelter to the local fauna. Carbonate blocks collected from the pockmarks showed evidence for three distinct generations including micritic Mg-calcite/aragonite, micritic aragonite, and botryoidal aragonite. The carbon isotopic values of these phases are 13C depleted and 18O enriched, indicating a methanogenic origin and possibly a component sourced from dissociation of gas hydrates. Water geochemistry from shallow cores within and outside the pockmarks gave no indication of active seepage. This conclusion is further supported by no direct observations of fluid flow within the pockmarks, no bacterial mats nor obvious chemosymbiotic communities. In addition, oxidized carbonate surfaces indicate a gradual excavation and exposure at the sea floor. We conclude that one of the world's largest pockmark fields is currently inactive and that its formation is likely related to deglaciation processes about 11 ky ago.

  13. 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

    PubMed Central

    2009-01-01

    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 of10B 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. PMID:20596476

  14. Current oscillations in semi-insulating GaAs associated with field-enhanced capture of electrons by the major deep donor EL2

    NASA Technical Reports Server (NTRS)

    Kaminska, M.; Parsey, J. M.; Lagowski, J.; Gatos, H. C.

    1982-01-01

    Current oscillations thermally activated by the release of electrons from deep levels in undoped semiinsulating GaAs were observed for the first time. They were attributed to electric field-enhanced capture of electrons by the dominant deep donor EL2 (antisite AsGa defect). This enhanced capture is due to the configurational energy barrier of EL2, which is readily penetrated by hot electrons.

  15. Full Scale Field Trial of the Low Temperature Mercury Capture Process

    SciTech Connect

    Locke, James; Winschel, Richard

    2012-05-21

    CONSOL Energy Inc., with partial funding from the Department of Energy (DOE) National Energy Technology Laboratory, designed a full-scale installation for a field trial of the Low-Temperature Mercury Control (LTMC) process, which has the ability to reduce mercury emissions from coal-fired power plants by over 90 percent, by cooling flue gas temperatures to approximately 230°F and absorbing the mercury on the native carbon in the fly ash, as was recently demonstrated by CONSOL R&D on a slip-stream pilot plant at the Allegheny Energy Mitchell Station with partial support by DOE. LTMC has the potential to remove over 90 percent of the flue gas mercury at a cost at least an order of magnitude lower (on a $/lb mercury removed basis) than activated carbon injection. The technology is suitable for retrofitting to existing and new plants, and, although it is best suited to bituminous coal-fired plants, it may have some applicability to the full range of coal types. Installation plans were altered and moved from the original project host site, PPL Martins Creek plant, to a second host site at Allegheny Energy's R. Paul Smith plant, before installation actually occurred at the Jamestown (New York) Board of Public Utilities (BPU) Samuel A. Carlson (Carlson) Municipal Generating Station Unit 12, where the LTMC system was operated on a limited basis. At Carlson, over 60% mercury removal was demonstrated by cooling the flue gas to 220-230°F at the ESP inlet via humidification. The host unit ESP operation was unaffected by the humidification and performed satisfactorily at low temperature conditions.

  16. 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.

  17. Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

    PubMed

    Andoh, T; Fujimoto, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Kawabata, S; Kirihata, M; Akisue, T; Yayama, K; Kurosaka, M; Miyatake, S; Fukumori, Y; Ichikawa, H

    2011-12-01

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  18. Synthesis and radiation dosimetry of 4-borono-2-[18F]fluoro-D,L-phenylalanine: a target compound for PET and boron neutron capture therapy.

    PubMed

    Ishiwata, K; Ido, T; Mejia, A A; Ichihashi, M; Mishima, Y

    1991-01-01

    The 18F-labeling of 4-borono-D-L-phenylalanine (BPA), a potential target compound for cancer treatment with boron neutron capture therapy, is described. By direct fluorination of BPA with [18F]AcOF or [18F]F2 followed by HPLC separation, 4-borono-2-[18F]fluoro-D,L-phenylalanine was prepared with radiochemical yields of 25-35% and with a radiochemical purity of over 99%. The tissue distribution study showed that the compound has potential as a tracer for pancreas imaging with positron emission tomography. Radiation dosimetry is also described.

  19. 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. PMID:18272285

  20. Preparation and characterization of Boron carbide nanoparticles for use as a novel agent in T cell-guided boron neutron capture therapy.

    PubMed

    Mortensen, M W; Sørensen, P G; Björkdahl, O; Jensen, M R; Gundersen, H J G; Bjørnholm, T

    2006-03-01

    Boron carbide nanoparticles are proposed as a system for T cell-guided boron neutron capture therapy. Nanoparticles were produced by ball milling in various atmospheres of commercially available boron carbide. The physical and chemical properties of the particles were investigated using transmission electron microscopy, photon correlation spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, vibrational spectroscopy, gel electrophoresis and chemical assays and reveal profound changes in surface chemistry and structural characteristics. In vitro thermal neutron irradiation of B16 melanoma cells incubated with sub-100 nm nanoparticles (381.5 microg/g (10)B) induces complete cell death. The nanoparticles alone induce no toxicity.

  1. Development of high intensity ion sources for a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

    PubMed

    Bergueiro, J; Igarzabal, M; Sandin, J C Suarez; Somacal, H R; Vento, V Thatar; Huck, H; Valda, A A; Repetto, M; Kreiner, A J

    2011-12-01

    Several ion sources have been developed and an ion source test stand has been mounted for the first stage of a Tandem-Electrostatic-Quadrupole facility For Accelerator-Based Boron Neutron Capture Therapy. A first source, designed, fabricated and tested is a dual chamber, filament driven and magnetically compressed volume plasma proton ion source. A 4 mA beam has been accelerated and transported into the suppressed Faraday cup. Extensive simulations of the sources have been performed using both 2D and 3D self-consistent codes.

  2. Boron neutron capture therapy of brain tumors: Enhanced survival following intracarotid injection of sodium borocaptate with or without blood-brain barrier disruption

    SciTech Connect

    Yang, W.; Barth, R.F.; Rotaru, J.H.

    1997-02-01

    Sodium borocaptate (Na{sub 2}B{sub 12}H{sub 11}SH or BSH) has been used clinically for boron neutron capture therapy (BNCT) of patients with primary brain tumors. The purpose of the present study was to determine if tumor uptake of BSH and efficacy of BNCT could be enhanced in F98 glioma-bearing rats by intracarotid (i.c.) injection of the compound with or without blood-brain barrier disruption (BBB-D). 56 refs., 4 figs., 3 tabs.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Boronated metalloporphyrins: a novel approach to the diagnosis and treatment of cancer using contrast-enhanced MR imaging and neutron capture therapy.

    PubMed

    Huang, L R; Straubinger, R M; Kahl, S B; Koo, M S; Alletto, J J; Mazurchuk, R; Chau, R I; Thamer, S L; Fiel, R J

    1993-01-01

    Porphyrins are a unique class of metal chelating agents that have shown specific affinity for neoplasms. The water-soluble free-base derivative, tetrakiscarborane carboxylate ester of 2,4-(alpha,beta-dihydroxyethyl) deuteroporphyrin IX (BOPP), an agent designed for neutron capture therapy, has previously demonstrated selective localization and retention in a C6 murine glioma. In the present work, the authors demonstrate that the manganese chelate of BOPP also selectively localizes in a rat 9L gliosarcoma and preferentially enhances the tumor-normal brain contrast of T1-weighted images for at least 92 hours. The data indicate a maximal enhancement of contrast between tumor and normal brain at 24 hours after injection, compared with 5 minutes for manganese (III) tetraphenylporphine sulfonate (TPPS4). The results also indicate that Mn-BOPP may have a slower uptake in the 9L glioma than Mn-TPPS4 but a longer retention in the tumor. Mn-BOPP is unique in that it represents, to the authors' knowledge, the first example of a single agent that can enhance contrast between tumor and normal tissue and be potentially effective as an agent for boron neutron capture therapy.

  9. Efforts in Increasing Racial and Ethnic Diversity in the Field of Art Therapy

    ERIC Educational Resources Information Center

    Awais, Yasmine J.; Yali, Ann Marie

    2015-01-01

    There is a clear need for greater diversity in the field of art therapy, with a particular need to increase the representation of racial and ethnic minorities in educational programs. In a sample of 16 art therapy program directors, strategies and barriers to recruitment were identified through an anonymous online survey. The results of the survey…

  10. Prolonged Field Care Working Group Fluid Therapy Recommendations.

    PubMed

    Baker, Benjamin L; Powell, Doug; Riesberg, Jamie; Keenan, Sean

    2016-01-01

    The Prolonged Field Care Working Group concurs that fresh whole blood (FWB) is the fluid of choice for patients in hemorrhagic shock, and the capability to transfuse FWB should be a basic skill set for Special Operations Forces (SOF) Medics. Prolonged field care (PFC) must also address resuscitative and maintenance fluid requirements in nonhemorrhagic conditions. PMID:27045508

  11. Effect of anatomical variability on electric field characteristics of electroconvulsive therapy and magnetic seizure therapy: a parametric modeling study.

    PubMed

    Deng, Zhi-De; Lisanby, Sarah H; Peterchev, Angel V

    2015-01-01

    Electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) are conventionally applied with a fixed stimulus current amplitude, which may result in differences in the neural stimulation strength and focality across patients due to interindividual anatomical variability. The objective of this study is to quantify the effect of head anatomical variability associated with age, sex, and individual differences on the induced electric field characteristics in ECT and MST. Six stimulation modalities were modeled including bilateral and right unilateral ECT, focal electrically administered seizure therapy (FEAST), and MST with circular, cap, and double-cone coils. The electric field was computed using the finite element method in a parameterized spherical head model representing the variability in the general population. Head tissue layer thicknesses and conductivities were varied to examine the impact of interindividual anatomical differences on the stimulation strength, depth, and focality. Skull conductivity most strongly affects the ECT electric field, whereas the MST electric field is independent of tissue conductivity variation in this model but is markedly affected by differences in head diameter. Focal ECT electrode configurations such as FEAST is more sensitive to anatomical variability than that of less focal paradigms such as BL ECT. In MST, anatomical variability has stronger influence on the electric field of the cap and circular coils compared to the double-cone coil, possibly due to the more superficial field of the former. The variability of the ECT and MST electric fields due to anatomical differences should be considered in the interpretation of existing studies and in efforts to improve dosing approaches for better control of stimulation strength and focality across patients, such as individualization of the current amplitude. The conventional approach to individualizing dosage by titrating the number of pulses cannot compensate for differences in

  12. 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.

  13. Spatial capture-recapture

    USGS Publications Warehouse

    Royle, J. Andrew; Chandler, Richard B.; Sollmann, Rahel; Gardner, Beth

    2013-01-01

    Spatial Capture-Recapture provides a revolutionary extension of traditional capture-recapture methods for studying animal populations using data from live trapping, camera trapping, DNA sampling, acoustic sampling, and related field methods. This book is a conceptual and methodological synthesis of spatial capture-recapture modeling. As a comprehensive how-to manual, this reference contains detailed examples of a wide range of relevant spatial capture-recapture models for inference about population size and spatial and temporal variation in demographic parameters. Practicing field biologists studying animal populations will find this book to be a useful resource, as will graduate students and professionals in ecology, conservation biology, and fisheries and wildlife management.

  14. 4-Borono-2-[18F]fluoro-D,L-phenylalanine as a target compound for boron neutron capture therapy: tumor imaging potential with positron emission tomography.

    PubMed

    Ishiwata, K; Ido, T; Kawamura, M; Kubota, K; Ichihashi, M; Mishima, Y

    1991-01-01

    We studied the tumor uptake and metabolism of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), an 18F-labeled target compound for boron neutron capture therapy. In mice bearing FM3A mammary carcinoma, the accumulation of [18F]FBPA in the FM3A for the first 2 h, and its decrease in all other tissues, resulted in high FM3A-to-tissue uptake ratios. In the FM3A, the tracer was stable for metabolic alteration, which was in contrast to the gradual increase of protein-bound radioactivity in plasma. Imaging of FM3A was demonstrated by whole body autoradiography. [18F]FBPA has potential for use as a PET tracer for tumor imaging with high contrast, even in the pancreas.

  15. Specific killing effect of 10B1-para-boronophenylalanine in thermal neutron capture therapy of malignant melanoma: in vitro radiobiological evaluation.

    PubMed

    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.

  16. 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.

  17. The effect of ionizing radiation on the blood-brain-barrier (BBB): Considerations for the application of Boron Neutron Capture Therapy (BNCT) of brain tumors

    SciTech Connect

    Dorn, R.V. III; Spickard, J.H.; Griebenow, M.L.

    1988-01-01

    All methods of Boron Neutron Capture Therapy (BNCT) in use or envisioned for treatment of brain tumors have an element of ionizing radiation (incident and induced). This paper reviews data on the effects of ionizing radiation on the blood-brain-barrier (BBB) and the blood-tumor-barrier (BTB) and the potential impact of the effects on the delivery techniques of BNCT. The objectives are: review the available technique for BNCT of brain tumors; review the literature on experimental and human studies regarding the effects of ionizing radiation on the BBB; discuss the impact of these effects on the fractionization question for BNCT; and draw conclusions from that information. 22 refs., 4 tabs.

  18. 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.

  19. Monitoring the distribution of prompt gamma rays in boron neutron capture therapy using a multiple-scattering Compton camera: A Monte Carlo simulation study

    NASA Astrophysics Data System (ADS)

    Lee, Taewoong; Lee, Hyounggun; Lee, Wonho

    2015-10-01

    This study evaluated the use of Compton imaging technology to monitor prompt gamma rays emitted by 10B in boron neutron capture therapy (BNCT) applied to a computerized human phantom. The Monte Carlo method, including particle-tracking techniques, was used for simulation. The distribution of prompt gamma rays emitted by the phantom during irradiation with neutron beams is closely associated with the distribution of the boron in the phantom. Maximum likelihood expectation maximization (MLEM) method was applied to the information obtained from the detected prompt gamma rays to reconstruct the distribution of the tumor including the boron uptake regions (BURs). The reconstructed Compton images of the prompt gamma rays were combined with the cross-sectional images of the human phantom. Quantitative analysis of the intensity curves showed that all combined images matched the predetermined conditions of the simulation. The tumors including the BURs were distinguishable if they were more than 2 cm apart.

  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. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: A finite element simulation study

    PubMed Central

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2014-01-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced maximum electric field in the brain of 2.1–2.5 V/cm and 1.1–2.2 V/cm, corresponding to 6.2–7.2 times and 1.2–2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much higher with ECT (up to 100%) than MST (up to 8.2%). MST with the double cone coil was the most focal and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800–900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects. PMID:21248385

  2. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study

    NASA Astrophysics Data System (ADS)

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2011-02-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm-1 and 1.1-2.2 V cm-1 in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.

  3. Monte Carlo study of MLC fields for cobalt therapy machine

    PubMed Central

    Ayyangar, Komanduri M.; Rani, Roopa A.; Kumar, Anil; Reddy, A. R.

    2014-01-01

    An automated Multi-Leaf Collimator (MLC) system has been developed as add-on for the cobalt-60 teletherapy machines available in India. The goal of the present computational study is to validate the MLC design using Monte Carlo (MC) modeling. The study was based on the Kirloskar-supplied Phoenix model machines that closely match the Atomic Energy of Canada Limited (AECL) theratron-80 machine. The MLC is a retrofit attachment to the collimator assembly, with 14 non-divergent leaf pairs of 40 mm thick, 7 mm wide, and 150 mm long tungsten alloy plates with rounded edges and 20 mm tongue and 2 mm groove in each leaf. In the present work, the source and collimator geometry has been investigated in detail to arrive at a model that best represents the measured dosimetric data. The authors have studied in detail the proto-I MLC built for cobalt-60. The MLC field sizes were MC simulated for 2 × 2 cm2 to 14 × 14 cm2 square fields as well as irregular fields, and the percent depth dose (PDD) and profile data were compared with ROPS† treatment planning system (TPS). In addition, measured profiles using the IMATRIXX system‡ were also compared with the MC simulations. The proto-I MLC can define radiation fields up to 14 × 14 cm2 within 3 mm accuracy. The maximum measured leakage through the leaf ends in closed condition was 3.4% and interleaf leakage observed was 7.3%. Good agreement between MC results, ROPS and IMATRIXX results has been observed. The investigation also supports the hypothesis that optical and radiation field coincidence exists for the square fields studied with the MLC. Plots of the percent depth dose (PDD) data and profile data for clinically significant irregular fields have also been presented. The MC model was also investigated to speed up the calculations to allow calculations of clinically relevant conformal beams. †Radiation Oncology Planning System (ROPS) is supplied by Tirumala Jyothi Computer Systems described at https

  4. Television system for verification and documentation of treatment fields during intraoperative radiation therapy.

    PubMed

    Fraass, B A; Harrington, F S; Kinsella, T J; Sindelar, W F

    1983-09-01

    Intraoperative radiation therapy (IORT) involves direct treatment of tumors or tumor beds with large single doses of radiation. The verification of the area to be treated before irradiation and the documentation of the treated area are critical for IORT, just as for other types of radiation therapy. A television system which allows the target area to be directly imaged immediately before irradiation has been developed. Verification and documentation of treatment fields has made the IORT television system indispensable.

  5. 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. PMID:25934274

  6. 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.

  7. 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.

  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. PMID:23334699

  9. NOTE: Intraoperative radiation therapy using a mobile electron linear accelerator: field matching for large-field electron irradiation

    NASA Astrophysics Data System (ADS)

    Beddar, A. S.; Briere, T. M.; Ouzidane, M.

    2006-09-01

    Intraoperative radiation therapy (IORT) consists of delivering a large, single-fraction dose of radiation to a surgically exposed tumour or tumour bed at the time of surgery. With the availability of a mobile linear accelerator in the OR, IORT procedures have become more feasible for medical centres and more accessible to cancer patients. Often the area requiring irradiation is larger than what the treatment applicators will allow, and therefore, two or more adjoining fields are used. Unfortunately, the divergence and scattering of the electron beams may cause significant dose variations in the region of the field junction. Furthermore, because IORT treatments are delivered in a large single fraction, the effects of underdosing or overdosing could be more critical when compared to fractionated external beam therapy. Proper matching of the fields is therefore an important technical aspect of treatment delivery. We have studied the matching region using the largest flat applicator available for three different possibilities: abutting the fields, leaving a small gap or creating an overlap. Measurements were done using film dosimetry for the available energies of 4, 6, 9 and 12 MeV. Our results show the presence of clinically significant cold spots for the low-energy beams when the fields are either gapped or abutted, suggesting that the fields should be overlapped. No fields should be gapped. The results suggest that an optimal dose distribution may be obtained by overlapping the fields at 4 and 6 MeV and simply abutting the fields at 9 and 12 MeV. However, due to uncertainties in the placement of lead shields during treatment delivery, one may wish to consider overlapping the higher energy fields as well.

  10. The Contributions of Wayne Ruppenthal to the Field of Music Therapy.

    PubMed

    Miller

    1999-01-01

    This paper examines the career of Wayne Ruppenthal, considered one of the early pioneers in the field of music therapy. He began his practice in the late 1940s and his clinical accomplishments at Topeka State Hospital, spanned nearly two decades during the height of Freudian psychoanalysis and "milieu" therapy prescribed by The Menninger Foundation. Ruppenthal received his education at The University of Kansas in Lawrence, Kansas, and was the first graduate of the Master's of Music Education in Functional Music program in 1948. His contributions to the profession were significant and enduring and included establishing formal clinical practice and training standards, assisting with development of the National Association for Music Therapy (NAMT), and promoting the credibility of music therapy through published research. He retired from Topeka State Hospital in 1968. This paper is dedicated to the memory of Wayne Ruppenthal, who died on August 31, 1997.

  11. Identification of Prey Captures in Australian Fur Seals (Arctocephalus pusillus doriferus) Using Head-Mounted Accelerometers: Field Validation with Animal-Borne Video Cameras.

    PubMed

    Volpov, Beth L; Hoskins, Andrew J; Battaile, Brian C; Viviant, Morgane; Wheatley, Kathryn E; Marshall, Greg; Abernathy, Kyler; Arnould, John P Y

    2015-01-01

    This study investigated prey captures in free-ranging adult female Australian fur seals (Arctocephalus pusillus doriferus) using head-mounted 3-axis accelerometers and animal-borne video cameras. Acceleration data was used to identify individual attempted prey captures (APC), and video data were used to independently verify APC and prey types. Results demonstrated that head-mounted accelerometers could detect individual APC but were unable to distinguish among prey types (fish, cephalopod, stingray) or between successful captures and unsuccessful capture attempts. Mean detection rate (true positive rate) on individual animals in the testing subset ranged from 67-100%, and mean detection on the testing subset averaged across 4 animals ranged from 82-97%. Mean False positive (FP) rate ranged from 15-67% individually in the testing subset, and 26-59% averaged across 4 animals. Surge and sway had significantly greater detection rates, but also conversely greater FP rates compared to heave. Video data also indicated that some head movements recorded by the accelerometers were unrelated to APC and that a peak in acceleration variance did not always equate to an individual prey item. The results of the present study indicate that head-mounted accelerometers provide a complementary tool for investigating foraging behaviour in pinnipeds, but that detection and FP correction factors need to be applied for reliable field application. PMID:26107647

  12. Identification of Prey Captures in Australian Fur Seals (Arctocephalus pusillus doriferus) Using Head-Mounted Accelerometers: Field Validation with Animal-Borne Video Cameras

    PubMed Central

    Volpov, Beth L.; Hoskins, Andrew J.; Battaile, Brian C.; Viviant, Morgane; Wheatley, Kathryn E.; Marshall, Greg; Abernathy, Kyler; Arnould, John P. Y.

    2015-01-01

    This study investigated prey captures in free-ranging adult female Australian fur seals (Arctocephalus pusillus doriferus) using head-mounted 3-axis accelerometers and animal-borne video cameras. Acceleration data was used to identify individual attempted prey captures (APC), and video data were used to independently verify APC and prey types. Results demonstrated that head-mounted accelerometers could detect individual APC but were unable to distinguish among prey types (fish, cephalopod, stingray) or between successful captures and unsuccessful capture attempts. Mean detection rate (true positive rate) on individual animals in the testing subset ranged from 67-100%, and mean detection on the testing subset averaged across 4 animals ranged from 82-97%. Mean False positive (FP) rate ranged from 15-67% individually in the testing subset, and 26-59% averaged across 4 animals. Surge and sway had significantly greater detection rates, but also conversely greater FP rates compared to heave. Video data also indicated that some head movements recorded by the accelerometers were unrelated to APC and that a peak in acceleration variance did not always equate to an individual prey item. The results of the present study indicate that head-mounted accelerometers provide a complementary tool for investigating foraging behaviour in pinnipeds, but that detection and FP correction factors need to be applied for reliable field application. PMID:26107647

  13. Influence of Preoperative Radiation Field on Postoperative Leak Rates in Esophageal Cancer Patients after Trimodality Therapy

    PubMed Central

    Juloori, Aditya; Tucker, Susan L.; Komaki, Ritsuko; Liao, Zhongxing; Correa, Arlene M.; Swisher, Stephen G.; Hofstetter, Wayne L.; Lin, Steven H.

    2014-01-01

    Introduction Postoperative morbidities, such as anastomotic leaks, are common after trimodality therapy (chemoradiation followed by surgery) for esophageal cancer. We investigated for factors associated with an increased incidence of anastomotic leaks. Methods Data from 285 esophageal cancer patients treated from 2000–2011 with trimodality therapy was analyzed. Anastomotic location relative to preoperative radiation field was assessed using postoperative computed tomographic imaging. Logistic regression was used to evaluate for factors associated with any or clinically relevant (CR) (≥ grade 2) leaks. Results Overall anastomotic leak rate was 11% (31/285), and CR leak rate was 6% (17/285). Multivariable analysis identified body mass index (BMI) (OR 1.09, 95%CI 1.00–1.17; OR 1.11, 95%CI 1.01–1.22), three-field surgery (OR 10.01, 95%CI 3.83–26.21; OR 4.83, 95%CI 1.39–16.71), and within radiation field (“in-field”) anastomosis (OR 5.37, 95%CI 2.21–13.04; OR 8.63, 95%CI 2.90–25.65) as independent predictors of both all grade and CR leaks, respectively. While patients with distal esophageal tumors and Ivor-Lewis surgery had the lowest incidence of all grade (6.5%) and CR leaks (4.2%), most of the leaks were associated with the anastomosis constructed within the field of radiation (in-field: 39% and 30% versus out-of-field: 2.6% and 1.0%, respectively, for total and CR leaks, p<0.0001, Fisher’s Exact test). Conclusions Esophagogastric anastomosis placed within the preoperative radiation field was a very strong predictor for anastomotic leaks in esophageal cancer patients treated with trimodality therapy, among other factors. Surgical planning should include a critical evaluation of the preoperative radiation fields to ensure proper anastomotic placement after chemoradiation therapy. PMID:24736077

  14. An Analysis of the Distribution and Economics of Oil Fields for Enhanced Oil Recovery-Carbon Capture and Storage

    NASA Astrophysics Data System (ADS)

    Hall, Kristyn Ann

    The rising carbon dioxide emissions contributing to climate change has lead to the examination of potential ways to mitigate the environmental impact. One such method is through the geological sequestration of carbon (CCS). Although there are several different forms of geological sequestration (i.e. Saline Aquifers, Oil and Gas Reservoirs, Unminable Coal Seams) the current projects are just initiating the large scale-testing phase. The lead entry point into CCS projects is to combine the sequestration with enhanced oil recovery (EOR) due to the improved economic model as a result of the oil recovery and the pre-existing knowledge of the geological structures. The potential scope of CCS-EOR projects throughout the continental United States in terms of a systematic examination of individual reservoir storage potential has not been examined. Instead the majority of the research completed has centered on either estimating the total United States storage potential or the potential of a single specific reservoir. The purpose of this paper is to examine the relationship between oil recovery, carbon dioxide storage and cost during CCS-EOR. The characteristics of the oil and gas reservoirs examined in this study from the Nehring Oil and Gas Database were used in the CCS-EOR model developed by Sean McCoy to estimate the lifting and storage costs of the different reservoirs throughout the continental United States. This allows for an examination of both technical and financial viability of CCS-EOR as an intermediate step for future CCS projects in other geological formations. One option for mitigating climate change is to store industrial CO2 emissions in geologic reservoirs as part of a process known as carbon capture and storage (CCS). There is general consensus that large-scale deployment of CCS would best be initiated by combining geologic sequestration with enhanced oil recovery (EOR), which can use CO2 to improve production from declining oil fields. Revenues from the

  15. Strategies for the design and synthesis of boronated nucleic acid and protein components as potential delivery agents for neutron capture therapy

    SciTech Connect

    Wyzlic, I.M.; Tjarks, W.; Soloway, A.H.; Anisuzzaman, A.K.M.; Rong, Feng-Guang; Barth, R.F. )

    1994-03-30

    Strategies for the design and synthesis of boronated nucleosides, amino acids, and peptides as potential delivery agents for boron neutron capture therapy (BNCT) are described. For BNCT to be a useful treatment modality, there is a need to design and synthesize nontoxic boron compounds that selectively target tumor cells, accumulate in sufficient amounts (20-30 [mu]g [sup 10]B/g of tumor) and persist at therapeutic levels for a sufficient time prior to neutron irradiation. Boronated nucleosides, amino acids and peptides are such promising target compounds. Such structures may be selectively used by proliferating neoplastic cells compared with mitotically less active normal cells and therefore achieve the tissue differentials necessary for BNCT. The rationale for synthesis of boronated nucleic acid and protein components is discussed. Results of biological and clinical studies of some boronated nucleosides, nucleotides, amino acids and peptides are presented. Boronated nucleosides, amino acids and peptides can be considered as potential targeting agents for BNCT. 96 refs., 4 figs.

  16. Pharmacokinetics in melanoma-bearing mice of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a candidate compound for boron neutron capture therapy.

    PubMed Central

    Verrijk, R.; Smolders, I. J.; Huiskamp, R.; Gavin, P. R.; Philipp, K. H.; Begg, A. C.

    1994-01-01

    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. PMID:8142252

  17. "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).

  18. 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. PMID:27467416

  19. 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.

  20. “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.

  1. Physicochemical investigation of the influence of saccharide-based parenteral formulation excipients on L-p-boronphenylalanine solubilisation for boron neutron capture therapy.

    PubMed

    Schmidt, Elke; Dooley, Neil; Ford, Steven J; Elliott, Moira; Halbert, Gavin W

    2012-01-01

    This paper investigates the physicochemical properties of possible pharmaceutical alternatives to L-p-boronphenylalanine (BPA)-fructose intravenous formulation currently employed in boron neutron capture therapy. The physicochemical properties of BPA in the absence and presence of fructose, mannitol, trehalose and hydroxypropyl-β-cyclodextrin (HPCD) was investigated by determination of pKa values, solubility, precipitation and dissolution using a Sirius T3 instrument. Complex formation was also assessed using (10) B-Nuclear magnetic resonance (NMR). The results indicate that fructose and mannitol form a complex with BPA through a reversible interaction with the boronic acid group, determined by changes in the pKa of the boronic acid group, the ultraviolet and NMR spectra, and increase in kinetic solubility. Trehalose and HPCD did not undergo this reaction and, consequently, did not affect boronphenylalanaine physicochemical properties. Although mannitol is complexed with BPA in an identical manner to fructose, it is superior because it provides increased kinetic solubility. Replacement of fructose by mannitol in the current clinical BPA formulation is, therefore, feasible with advantages of increased dosing and removal of issues related to fructose intolerance and calorific load. Results also indicated that important pharmaceutical parameters are the complex's solubility and dissociation behaviours rather than, as originally assumed, the complex formation reaction. PMID:21918989

  2. 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.

  3. Evaluation of Moringa oleifera seed lectin in traps for the capture of Aedes aegypti eggs and adults under semi-field conditions.

    PubMed

    Santos, Nataly Diniz de Lima; Paixão, Kelly da Silva; Napoleão, Thiago Henrique; Trindade, Priscila Barbi; Pinto, Mariele Ribeiro; Coelho, Luana Cassandra Breitenbach Barroso; Eiras, Álvaro Eduardo; Navarro, Daniela Maria do Amaral Ferraz; Paiva, Patrícia Maria Guedes

    2014-05-01

    The water-soluble lectin isolated from Moringa oleifera seeds (WSMoL) is a larvicidal, ovicidal, and oviposition-stimulating agent against Aedes aegypti under laboratory conditions. This study investigated the effect of WSMoL in traps for the capture of A. aegypti eggs and adult females under semi-field conditions and determined whether gravid females could detect WSMoL by an olfactory response. WSMoL was isolated according to a previously described procedure using chitin chromatography. The bioassays were performed in large cages (12.5 m(3)). Two traps for collection of eggs (ovitrap) or adult mosquitoes (MosquiTRAP(TM)) were placed in a cage. One was filled with WSMoL (0.1 mg/mL) and the other with tap water (negative control). An infusion of Panicum maximum leaves was used as a positive control. Forty gravid females were then released in each cage. After 2 (for oviposition) or 3 h (for female capture), the traps were removed, and the number of eggs or females was counted. An olfactometry assay was performed to investigate whether the effect of WSMoL on gravid females was linked to an olfactory response. WSMoL showed an oviposition-stimulating effect (65 ± 14%) that was similar (p < 0.05) to that promoted by the P. maximum infusion (67 ± 11%). The efficiency of MosquiTRAP(TM) in capturing gravid females was not increased by WSMoL. The olfactometry assay indicated that the response of females to WSMoL did not involve the stimulation of olfactory sensilla. WSMoL effectively captured eggs when used in ovitraps under semi-field conditions; this property, together with the ovicidal and larvicidal activities of this lectin, makes it an interesting candidate for A. aegypti control. PMID:24604386

  4. Trap capture of three economically important fruit fly species (Diptera: Tephritidae): evaluation of a solid formulation containing multiple male lures in a Hawaiian coffee field.

    PubMed

    Shelly, Todd; Nishimoto, Jon; Kurashima, Rick

    2012-08-01

    Invasive fruit flies (Diptera: Tephritidae) pose a global threat to agriculture through direct damage to food crops and the accompanying trade restrictions that often result. Early detection is vital to controlling fruit flies, because it increases the probability of limiting the growth and spread of the invasive population and thus may greatly reduce the monetary costs required for eradication or suppression. Male-specific lures are an important component of fruit fly detection, and three such lures are used widely: trimedlure (TML), cue lure (CL), and methyl eugenol (ME), attractive to Mediterranean fruit fly, Ceratitis capitata (Wiedemann); melon fly, Bactrocera cucurbitae (Coquillett); and oriental fruit fly, Bactrocera dorsalis (Hendel), respectively. In California, Florida, and Texas, the two Bactrocera lures are applied to separate species-specific traps as liquids (with a small amount of the insecticide naled added), whereas TML is delivered as a solid plug in another set of traps. Thus, the detection protocol involves considerable handling time as well as potential contact with a pesticide. The purpose of this study was to compare trap capture between liquid male lures and "trilure" wafers that contain TML, ME, raspberry ketone (RK, the hydroxy equivalent of CL), and the toxicant DDVP embedded within a solid matrix. Field studies were conducted in a Hawaiian coffee (Coffea arabica L.) field where the three aforementioned species co-occur, showed that the wafer captured at least as many flies as the liquid baits for all three species. This same result was obtained in comparisons using both fresh and aged (6-wk) baits. Moreover, the wafers performed as well as the single-lure traps in an ancillary experiment in which TML plugs were substituted for liquid TML. Additional experiments demonstrated explicitly that the presence of ME and RK had no effect on captures of C. capitata males and similarly that the presence of TML had no effect on the capture of B

  5. Field match verification during combination proton, photon, and electron therapy for oligometastatic inflammatory breast cancer

    SciTech Connect

    Amos, Richard A.; Woodward, Wendy A.

    2012-01-01

    Postmastectomy radiation therapy (PMRT) has been shown in randomized trials to improve overall survival for patients with locally advanced breast cancer. The standard PMRT clinical target volume (CTV) encompasses the chest wall and undissected regional lymphatics. Conformal isodose distributions covering the standard CTV with acceptable dose limits to normal tissue can typically be achieved with a combination of photon and electron fields. Field borders are marked on the patient's skin using a light field projection of each beam and are subsequently used to verify daily field matching clinically. Initial imaging of a patient with oligometastatic inflammatory breast cancer demonstrated direct extension of disease from the involved internal mammary lymph node chain into the anterior mediastinum as the only site of metastatic disease. The patient achieved a pathologic complete response to neoadjuvant chemotherapy and underwent mastectomy. The initial sites of gross disease, including the anterior mediastinal node was included in the CTV for PMRT, and treatment planning demonstrated a clear advantage to the inclusion of proton fields in this case. The absence of a light source on the proton delivery system that accurately projects proton field edges onto the patient's skin posed a significant challenge for daily verification of proton-to-photon and -electron field matching. Proton field-specific radiographic imaging devices were designed and used such that proton field edges could be delineated on the patient's skin and used for daily matching with photon and electron fields. Manufacture of the imaging devices was quick and inexpensive. Weekly verification of proton field alignment with the proton field delineation on the skin demonstrated agreement within 3-mm tolerance. The patient remains with no evidence of disease 18 months after completing radiation. Other patients with similar indications may benefit from multimodality radiation therapy.

  6. A robust procedure for verifying TomoTherapy Hi-Art™ source models for small fields

    NASA Astrophysics Data System (ADS)

    Hundertmark, B.; Sterpin, E.; Mackie, T.

    2011-06-01

    The dosimetric measurement and modeling of small radiation treatment fields (<2 × 2 cm2) are difficult to perform and prone to error. Measurements of small fields are often adversely influenced by the properties of the detectors used to make them. The dosimetric properties of small fields have been difficult to accurately model due to the effects of source occlusion caused by the collimating jaws. In this study, small longitudinal slice widths (SWs) of the TomoTherapy® Hi-Art® machine are characterized by performing dosimetric measurements topographically. By using a static gantry, opening the central 16 MLC leaves during the irradiations, and symmetrically scanning detectors 10 cm through each longitudinal SW, integral doses to a 'TomoTherapy equivalent' 10 × 10 cm2 area are topographically measured. To quantify the effects of source occlusion for TomoTherapy, a quantity referred to as the integral scanned dose to slice width ratio (D/SW) is introduced. (D/SW) ratios are measured for SWs ranging from 0.375 to 5 cm in size using ion chambers and a radiographic film. The measurements of the (D/SW) ratio are shown to be insensitive to the detectors used in this study. The (D/SW) ratios for TomoTherapy have values of unity in the range of SW sizes from 5 cm to approximately 2 cm. For SWs smaller than 2 cm in size, the source-occlusion effect substantially reduces the measured machine output and the value of the (D/SW) ratios. The topographic measurement method presented provides a way to directly evaluate the accuracy of the small-field source model parameters used in dose calculation algorithms. As an example, the electron source spot size of a Penelope Monte Carlo (MC) model of TomoTherapy was varied to match computed and measured (D/SW) ratios. It was shown that the MC results for small SW sizes were sensitive to that particular parameter.

  7. Dose distributions in a human head phantom for neutron capture therapy using moderated neutrons from the 2.5 MeV proton-7Li reaction or from fission of 235U

    NASA Astrophysics Data System (ADS)

    Tanaka, Kenichi; Kobayashi, Tooru; Sakurai, Yoshinori; Nakagawa, Yoshinobu; Endo, Satoru; Hoshi, Masaharu

    2001-10-01

    The feasibility of neutron capture therapy (NCT) using an accelerator-based neutron source of the 7Li(p,n) reaction produced by 2.5 MeV protons was investigated by comparing the neutron beam tailored by both the Hiroshima University radiological research accelerator (HIRRAC) and the heavy water neutron irradiation facility in the Kyoto University reactor (KUR-HWNIF) from the viewpoint of the contamination dose ratios of the fast neutrons and the gamma rays. These contamination ratios to the boron dose were estimated in a water phantom of 20 cm diameter and 20 cm length to simulate a human head, with experiments by the same techniques for NCT in KUR-HWNIF and/or the simulation calculations by the Monte Carlo N-particle transport code system version 4B (MCNP-4B). It was found that the 7Li(p,n) neutrons produced by 2.5 MeV protons combined with 20, 25 or 30 cm thick D2O moderators of 20 cm diameter could make irradiation fields for NCT with depth-dose characteristics similar to those from the epithermal neutron beam at the KUR-HWNIF.

  8. A Classification of the Field of Family Therapy: A Review of Prior Attempts and a New Paradigmatic Model.

    ERIC Educational Resources Information Center

    Levant, Ronald F.

    1980-01-01

    Reviews early attempts to classify the field of family therapy, including Haley's caricatures, the Group for the Advancement of Psychiatry's classification, and others. The new paradigmatic model proposes a classification of the field of family therapy in terms of three therapeutic paradigms: the historical, the structure/process, and the…

  9. Enhanced capture of magnetic microbeads using combination of reduced magnetic field strength and sequentially switched electroosmotic flow--a numerical study.

    PubMed

    Das, Debarun; Al-Rjoub, Marwan F; Banerjee, Rupak K

    2015-05-01

    Magnetophoretic immunoassay is a widely used technique in lab-on-chip systems for detection and isolation of target cells, pathogens, and biomolecules. In this method, target pathogens (antigens) bind to specific antibodies coated on magnetic microbeads (mMBs) which are then separated using an external magnetic field for further analysis. Better capture of mMB is important for improving the sensitivity and performance of magnetophoretic assay. The objective of this study was to develop a numerical model of magnetophoretic separation in electroosmotic flow (EOF) using magnetic field generated by a miniaturized magnet and to evaluate the capture efficiency (CE) of the mMBs. A finite-volume solver was used to compute the trajectory of mMBs under the coupled effects of EOF and external magnetic field. The effect of steady and time varying (switching) electric fields (150-450 V/cm) on the CE was studied under reduced magnetic field strength. During switching, the electric potential at the inlet and outlet of the microchannel was reversed or switched, causing reversal in flow direction. The CE was a function of the momentum of the mMB in EOF and the applied magnetic field strength. By switching the electric field, CE increased from 75% (for steady electric field) to 95% for lower electric fields (150-200 V/cm) and from 35% to 47.5% for higher electric fields (400-450 V/cm). The CE was lower at higher EOF electric fields because the momentum of the mMB overcame the external magnetic force. Switching allowed improved CE due to the reversal and decrease in EOF velocity and increase in mMB residence time under the reduced magnetic field strength. These improvements in CE, particularly at higher electric fields, made sequential switching of EOF an efficient separation technique of mMBs for use in high throughput magnetophoretic immunoassay devices. The reduced size of the magnet, along with the efficient mMB separation technique of switching can lead to the development

  10. Quantitative approach to skin field cancerization using a nanoencapsulated photodynamic therapy agent: a pilot study

    PubMed Central

    Passos, Simone K; de Souza, Paulo EN; Soares, Priscila KP; Eid, Danglades RM; Primo, Fernando L; Tedesco, Antonio Cláudio; Lacava, Zulmira GM; Morais, Paulo C

    2013-01-01

    Background This paper introduces a new nanoformulation of 5-aminolevulinic acid (nano-ALA) as well as a novel quantitative approach towards evaluating field cancerization for actinic keratosis and/or skin photodamage. In this pilot study, we evaluated field cancerization using nano-ALA and methyl aminolevulinate (MAL), the latter being commercialized as Metvix®. Methods and results Photodynamic therapy was used for the treatment of patients with selected skin lesions, whereas the fluorescence of the corresponding photosensitizer was used to evaluate the time evolution of field cancerization in a quantitative way. Field cancerization was quantified using newly developed color image segmentation software. Using photodynamic therapy as the precancer skin treatment and the approach introduced herein for evaluation of fluorescent area, we found that the half-life of field cancerization reduction was 43.3 days and 34.3 days for nano-ALA and MAL, respectively. We also found that nano-ALA targeted about 45% more skin lesion areas than MAL. Further, we found the mean reduction in area of skin field cancerization was about 10% greater for nano-ALA than for MAL. Conclusion Although preliminary, our findings indicate that the efficacy of nano-ALA in treating skin field cancerization is higher than that of MAL. PMID:23450821

  11. Matching Intensity-Modulated Radiation Therapy to an Anterior Low Neck Field

    SciTech Connect

    Amdur, Robert J. Liu, Chihray; Li, Jonathan; Mendenhall, William; Hinerman, Russell

    2007-10-01

    When using intensity-modulated radiation therapy (IMRT) to treat head and neck cancer with the primary site above the level of the larynx, there are two basic options for the low neck lymphatics: to treat the entire neck with IMRT, or to match the IMRT plan to a conventional anterior 'low neck' field. In view of the potential advantages of using a conventional low neck field, it is important to look for ways to minimize or manage the problems of matching IMRT to a conventional radiotherapy field. Treating the low neck with a single anterior field and the standard larynx block decreases the dose to the larynx and often results in a superior IMRT plan at the primary site. The purpose of this article is to review the most applicable studies and to discuss our experience with implementing a technique that involves moving the position of the superior border of the low neck field several times during a single treatment fraction.

  12. Monitoring oral temperature, heart rate, and respiration rate of West Indian manatees (Trichechus manatus) during capture and handling in the field

    USGS Publications Warehouse

    Wong, Arthur W.; Bonde, Robert K.; Siegal-Willott, Jessica; Stamper, M. Andrew; Colee, James; Powell, James A.; Reid, James P.; Deutsch, Charles J.; Harr, Kendal E.

    2012-01-01

    West Indian manatees (Trichechus manatus) are captured, handled, and transported to facilitate conservation, research, and rehabilitation efforts. Monitoring manatee oral temperature (OT), heart rate (HR), and respiration rate (RR) during out-of-water handling can assist efforts to maintain animal well-being and improve medical response to evidence of declining health. To determine effects of capture on manatee vital signs, we monitored OT, HR, and RR continuously for a 50-min period in 38 healthy, awake, juvenile and adult Florida manatees (T. m. latirostris) and 48 similar Antillean manatees (T. m. manatus). We examined creatine kinase (CK), potassium (K+), serum amyloid A (SAA), and lactate values for each animal to assess possible systemic inflammation and muscular trauma. OT range was 29.5 to 36.2° C, HR range was 32 to 88 beats/min, and RR range was 0 to 17 breaths/5 min. Antillean manatees had higher initial OT, HR, and RR than Florida manatees (p < 0.001). As monitoring time progressed, mean differences between the subspecies were no longer significant. High RR over monitoring time was associated with high lactate concentration. Antillean manatees had higher overall lactate values ([mean ± SD] 20.6 ± 7.8 mmol/L) than Florida manatees (13.7 ± 6.7 mmol/L; p < 0.001). We recommend monitoring manatee OT, HR, and RR during capture and handling in the field or in a captive care setting.

  13. An Overview of Alternating Electric Fields Therapy (NovoTTF Therapy) for the Treatment of Malignant Glioma.

    PubMed

    Swanson, Kenneth D; Lok, Edwin; Wong, Eric T

    2016-01-01

    As with many cancer treatments, tumor treating fields (TTFields) target rapidly dividing tumor cells. During mitosis, TTFields-exposed cells exhibit uncontrolled membrane blebbing at the onset of anaphase, resulting in aberrant mitotic exit. Based on these criteria, at least two protein complexes have been proposed as TTFields' molecular targets, including α/β-tubulin and the septin 2, 6, 7 heterotrimer. After aberrant mitotic exit, cells exhibited abnormal nuclei and signs of cellular stress, including decreased cellular proliferation and p53 dependence, and exhibit the hallmarks of immunogenic cell death, suggesting that TTFields treatment may induce an antitumor immune response. Clinical trials lead to Food and Drug Administration approval for their treatment of recurrent glioblastoma. Detailed modeling of TTFields within the brain suggests that the location of the tumor may affect treatment efficacy. These observations have a profound impact on the use of TTFields in the clinic, including what co-therapies may be best applied to boost its efficacy.

  14. Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

    SciTech Connect

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

    2012-01-01

    Purpose: To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy. Methods and Materials: In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by use of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%). Conclusions: Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent. Toxicity was

  15. Impact of intra-arterial administration of boron compounds on dose-volume histograms in boron neutron capture therapy for recurrent head-and-neck tumors

    SciTech Connect

    Suzuki, Minoru . E-mail: msuzuki@rri.kyoto-u.ac.jp; Sakurai, Yoshinori; Nagata, Kenji; Kinashi, Yuko; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira; Kato, Ituro; Fuwa, Nobukazu; Hiratsuka, Junichi; Imahori, Yoshio

    2006-12-01

    Purpose: To analyze the dose-volume histogram (DVH) of head-and-neck tumors treated with boron neutron capture therapy (BNCT) and to determine the advantage of the intra-arterial (IA) route over the intravenous (IV) route as a drug delivery system for BNCT. Methods and Materials: Fifteen BNCTs for 12 patients with recurrent head-and-neck tumors were included in the present study. Eight irradiations were done after IV administration of boronophenylalanine and seven after IA administration. The maximal, mean, and minimal doses given to the gross tumor volume were assessed using a BNCT planning system. Results: The results are reported as median values with the interquartile range. In the IA group, the maximal, mean, and minimal dose given to the gross tumor volume was 68.7 Gy-Eq (range, 38.8-79.9), 45.0 Gy-Eq (range, 25.1-51.0), and 13.8 Gy-Eq (range, 4.8-25.3), respectively. In the IV group, the maximal, mean, and minimal dose given to the gross tumor volume was 24.2 Gy-Eq (range, 21.5-29.9), 16.4 Gy-Eq (range, 14.5-20.2), and 7.8 Gy-Eq (range, 6.8-9.5), respectively. Within 1-3 months after BNCT, the responses were assessed. Of the 6 patients in the IV group, 2 had a partial response, 3 no change, and 1 had progressive disease. Of 4 patients in the IA group, 1 achieved a complete response and 3 a partial response. Conclusion: Intra-arterial administration of boronophenylalanine is a promising drug delivery system for head-and-neck BNCT.

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

    PubMed Central

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

    2015-01-01

    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, ATB0,+, 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 ATB0,+ became significant at 1000 μM, accounting for 20–25% of the total BPA uptake in MCF-7 breast cancer cells. ATB0,+, 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 ATB0,+, respectively, differentiate their roles in BPA uptake. ATB0,+, as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose. PMID:25580517

  17. 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.

  18. Effect of Smaller Left Ventricular Capture Threshold Safety Margins to Improve Device Longevity in Recipients of Cardiac Resynchronization-Defibrillation Therapy

    PubMed Central

    Steinhaus, Daniel A.; Waks, Jonathan W.; Collins, Robert; Kleckner, Karen; Kramer, Daniel B.; Zimetbaum, Peter J.

    2015-01-01

    Device longevity in cardiac resynchronization therapy (CRT) is affected by the pacing capture threshold (PCT) and programmed pacing amplitude of the left ventricular (LV) pacing lead. The aims of this study were to evaluate the stability of LV pacing thresholds in a nationwide sample of CRT defibrillator recipients and to determine potential longevity improvements associated with a decrease in the LV safety margin while maintaining effective delivery of CRT. CRT defibrillator patients in the Medtronic CareLink database were eligible for inclusion. LV PCT stability was evaluated using ≥2 measurements over a 14-day period. Separately, a random sample of 7,250 patients with programmed right atrial and right ventricular amplitudes ≤2.5 V, LV thresholds ≤ 2.5 V, and LV pacing ≥90% were evaluated to estimate theoretical battery longevity improvement using LV safety margins of 0.5 and 1.5 V. Threshold stability analysis in 43,256 patients demonstrated LV PCT stability of <0.5 V in 77% of patients and <1 V in 95%. Device longevity analysis showed that the use of a 0.5-V safety margin increased average battery longevity by 0.62 years (95% confidence interval 0.61 to 0.63) compared with a safety margin of 1.5 V. Patients with LV PCTs >1 V had the greatest increases in battery life (mean increase 0.86 years, 95% confidence interval 0.85 to 0.87). In conclusion, nearly all CRT defibrillator patients had LV PCT stability <1.0 V. Decreasing the LV safety margin from 1.5 to 0.5 V provided consistent delivery of CRT for most patients and significantly improved battery longevity. PMID:25933732

  19. 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

  20. 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.

  1. 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%. PMID:25349432

  2. Boron uptake in normal melanocytes and melanoma cells and boron biodistribution study in mice bearing B16F10 melanoma for boron neutron capture therapy.

    PubMed

    Faião-Flores, Fernanda; Coelho, Paulo Rogério Pinto; Arruda-Neto, João Dias Toledo; Camillo, Maria Aparecida Pires; Maria-Engler, Silvya Stuchi; Rici, Rose Eli Grassi; Sarkis, Jorge Eduardo Souza; Maria, Durvanei Augusto

    2012-08-01

    Information on (10)B distribution in normal tissues is crucial to any further development of boron neutron capture therapy (BNCT). The goal of this study was to investigate the in vitro and in vivo boron biodistribution in B16F10 murine melanoma and normal tissues as a model for human melanoma treatment by a simple and rapid colorimetric method, which was validated by HR-ICP-MS. The B16F10 melanoma cell line showed higher melanin content than human melanocytes, demonstrating a greater potential for boronophenylalanine uptake. The melanocytes showed a moderate viability decrease in the first few minutes after BNCT application, stabilizing after 75 min, whereas the B16F10 melanoma showed the greatest intracellular boron concentration at 150 min after application, indicating a different boron uptake of melanoma cells compared to normal melanocytes. Moreover, at this time, the increase in boron uptake in melanoma cells was approximately 1.6 times higher than that in normal melanocytes. The (10)B concentration in the blood of mice bearing B16F10 melanoma increased until 90 min after BNCT application and then decreased after 120 min, and remained low until the 240th minute. On the other hand, the (10)B concentration in tumors was increased from 90 min and maximal at 150 min after application, thus confirming the in vitro results. Therefore, the present in vitro and in vivo study of (10)B uptake in normal and tumor cells revealed important data that could enable BNCT to be possibly used as a treatment for melanoma, a chemoresistant cancer associated with high mortality.

  3. The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulating decahydrodecaborate-{sup 1}B (GB-10) as {sup 1}B-carriers for boron neutron capture therapy

    SciTech Connect

    Masunaga, Shin-ichiro . E-mail: smasuna@rri.kyoto-u.ac.jp; Kasaoka, Satoshi; Maruyama, Kazuo; Nigg, David; Sakurai, Yoshinori; Nagata, Kenji; Suzuki, Minoru; Kinashi, Yuko; Maruhashi, Akira; Ono, Koji

    2006-12-01

    Purpose: To evaluate GB-10-encapsulating transferrin (TF)-pendant-type polyethyleneglycol (PEG) liposomes as tumor-targeting {sup 1}B-carriers for boron neutron capture therapy. Methods and Materials: A free mercaptoundecahydrododecaborate-{sup 1}B (BSH) or decahydrodecaborate-{sup 1}B (GB-10) solution, bare liposomes, PEG liposomes, or TF-PEG liposomes were injected into SCC VII tumor-bearing mice, and {sup 1}B concentrations in the tumors and normal tissues were measured by {gamma}-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating cells, then injected with these {sup 1}B-carriers containing BSH or GB-10 in the same manner. Right after thermal neutron irradiation, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The frequency in the total tumor cells was determined from the BrdU nontreated tumors. Results: Transferrin-PEG liposomes showed a prolonged retention in blood circulation, low uptake by reticuloendothelial system, and the most enhanced accumulation of {sup 1}B in solid tumors. In general, the enhancing effects were significantly greater in total cells than Q cells. In both cells, the enhancing effects of GB-10-containing {sup 1}B-carriers were significantly greater than BSH-containing {sup 1}B-carriers, whether loaded in free solution or liposomes. In both cells, whether BSH or GB-10 was employed, the greatest enhancing effect was observed with TF-PEG liposomes followed in decreasing order by PEG liposomes, bare liposomes, and free BSH or GB-10 solution. In Q cells, the decrease was remarkable between PEG and bare liposomes. Conclusions: In terms of biodistribution characteristics and tumor cell-killing effect as a whole, including Q cells, GB-10 TF-PEG liposomes were regarded as promising {sup 1}B-carriers.

  4. 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%.

  5. Synthesis, chemical and enzymatic hydrolysis, and aqueous solubility of amino acid ester prodrugs of 3-carboranyl thymidine analogs for boron neutron capture therapy of brain tumors.

    PubMed

    Hasabelnaby, Sherifa; Goudah, Ayman; Agarwal, Hitesh K; abd Alla, Mosaad S M; Tjarks, Werner

    2012-09-01

    Various water-soluble L-valine-, L-glutamate-, and glycine ester prodrugs of two 3-Carboranyl Thymidine Analogs (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 48-6600 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

  6. Does Pulsed Magnetic Field Therapy Influence Nerve Regeneration in the Median Nerve Model of the Rat?

    PubMed Central

    Beck-Broichsitter, Benedicta E.; Lamia, Androniki; Fregnan, Federica; Smeets, Ralf; Becker, Stephan T.; Sinis, Nektarios

    2014-01-01

    The aim of this study was to evaluate the impact of pulsed magnetic field therapy on peripheral nerve regeneration after median nerve injury and primary coaptation in the rat. Both median nerves were surgically exposed and denervated in 24 female Wistar rats. A microsurgical coaptation was performed on the right side, whereas on the left side a spontaneous healing was prevented. The study group underwent a daily pulsed magnetic field therapy; the other group served as a control group. The grasping force was recorded 2 weeks after the surgical intervention for a period of 12 weeks. The right median nerve was excised and histologically examined. The histomorphometric data and the functional assessments were analyzed by t-test statistics and one-way ANOVA. One-way ANOVA indicated a statistically significant influence of group affiliation and grasping force (P = 0.0078). Grasping strength was higher on a significant level in the experimental group compared to the control group permanently from the 9th week to the end of the study. T-test statistics revealed a significantly higher weight of the flexor digitorum sublimis muscle (P = 0.0385) in the experimental group. The histological evaluation did not reveal any statistically significant differences concerning the histomorphometric parameters. Our results suggest that the pulsed magnetic field therapy has a positive influence on the functional aspects of neural regeneration. More studies are needed to precisely evaluate and optimize the intensity and duration of the application. PMID:25143937

  7. Use of conductive gels for electric field homogenization increases the antitumor efficacy of electroporation therapies

    NASA Astrophysics Data System (ADS)

    Ivorra, Antoni; Al-Sakere, Bassim; Rubinsky, Boris; Mir, Lluis M.

    2008-11-01

    Electroporation is used in tissue for gene therapy, drug therapy and minimally invasive tissue ablation. The electrical field that develops during the application of the high voltage pulses needs to be precisely controlled. In the region to be treated, it is desirable to generate a homogeneous electric field magnitude between two specific thresholds whereas in other regions the field magnitude should be as low as possible. In the case of irregularly shaped tissue structures, such as bulky tumors, electric field homogeneity is almost impossible to be achieved with current electrode arrangements. We propose the use of conductive gels, matched to the conductivity of the tissues, to fill dead spaces between plate electrodes gripping the tissue so that the electric field distribution becomes less heterogeneous. Here it is shown that this technique indeed improves the antitumor efficacy of electrochemotherapy in sarcomas implanted in mice. Furthermore, we analyze, through finite element method simulations, how relevant the conductivity mismatches are. We found that conductivity mismatching errors are surprisingly well tolerated by the technique. Gels with conductivities ranging from 5 mS cm-1 to 10 mS cm-1 will be a proper solution for most cases.

  8. How Far Can the Red Palm Weevil (Coleoptera: Curculionidae) Fly?: Computerized Flight Mill Studies With Field-Captured Weevils.

    PubMed

    Hoddle, M S; Hoddle, C D; Faleiro, J R; El-Shafie, H A F; Jeske, D R; Sallam, A A

    2015-12-01

    Adult Rhynchophorus ferrugineus (Olivier) captured in pheromone-baited traps in commercial date palm orchards in the Al Ahsaa Directorate, Kingdom of Saudi Arabia, were used in computerized flight mill studies to determine the flight characteristics of this highly invasive and destructive palm pest. Flight mill studies were run at three different time periods, winter (December), spring (March), and summer (May). Of the 192 weevils tethered to flight mills ∼30% failed to fly > 1 km. Of those weevils flying > 1 km (n = 139), 55% flew > 10 km, and of these flyers 5% flew > 50 km in 24 h. Flying weevils exhibited an average weight loss of 20-30% and nonflying control weevils lost ∼9-13% body weight in 24 h. Male and female weevils flying in summer (average laboratory temperature was ∼27°C) flew the longest average distances (∼25-35 km), exhibited highest weight reductions (∼30%), and greatest mortality rates (∼80%). Consequently, time of year not weevil sex or color morph had a consistent and significant effect on flight activity, weight loss, and survivorship rates. Flight activity was predominantly diurnal commencing around 5:00 a.m. and peaking between 9-11:00 a.m. before tapering off. The distribution of flight distances combined across season and sex was mesokurtic (i.e., normally distributed).

  9. A hybrid actuated microrobot using an electromagnetic field and flagellated bacteria for tumor-targeting therapy.

    PubMed

    Li, Donghai; Choi, Hyunchul; Cho, Sunghoon; Jeong, Semi; Jin, Zhen; Lee, Cheong; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

    2015-08-01

    In this paper, we propose a new concept for a hybrid actuated microrobot for tumor-targeting therapy. For drug delivery in tumor therapy, various electromagnetic actuated microrobot systems have been studied. In addition, bacteria-based microrobot (so-called bacteriobot), which use tumor targeting and the therapeutic function of the bacteria, has also been proposed for solid tumor therapy. Compared with bacteriobot, electromagnetic actuated microrobot has larger driving force and locomotive controllability due to their position recognition and magnetic field control. However, because electromagnetic actuated microrobot does not have self-tumor targeting, they need to be controlled by an external magnetic field. In contrast, the bacteriobot uses tumor targeting and the bacteria's own motility, and can exhibit self-targeting performance at solid tumors. However, because the propulsion forces of the bacteria are too small, it is very difficult for bacteriobot to track a tumor in a vessel with a large bloodstream. Therefore, we propose a hybrid actuated microrobot combined with electromagnetic actuation in large blood vessels with a macro range and bacterial actuation in small vessels with a micro range. In addition, the proposed microrobot consists of biodegradable and biocompatible microbeads in which the drugs and magnetic particles can be encapsulated; the bacteria can be attached to the surface of the microbeads and propel the microrobot. We carried out macro-manipulation of the hybrid actuated microrobot along a desired path through electromagnetic field control and the micro-manipulation of the hybrid actuated microrobot toward a chemical attractant through the chemotaxis of the bacteria. For the validation of the hybrid actuation of the microrobot, we fabricated a hydrogel microfluidic channel that can generate a chemical gradient. Finally, we evaluated the motility performance of the hybrid actuated microrobot in the hydrogel microfluidic channel. We expect

  10. A hybrid actuated microrobot using an electromagnetic field and flagellated bacteria for tumor-targeting therapy.

    PubMed

    Li, Donghai; Choi, Hyunchul; Cho, Sunghoon; Jeong, Semi; Jin, Zhen; Lee, Cheong; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

    2015-08-01

    In this paper, we propose a new concept for a hybrid actuated microrobot for tumor-targeting therapy. For drug delivery in tumor therapy, various electromagnetic actuated microrobot systems have been studied. In addition, bacteria-based microrobot (so-called bacteriobot), which use tumor targeting and the therapeutic function of the bacteria, has also been proposed for solid tumor therapy. Compared with bacteriobot, electromagnetic actuated microrobot has larger driving force and locomotive controllability due to their position recognition and magnetic field control. However, because electromagnetic actuated microrobot does not have self-tumor targeting, they need to be controlled by an external magnetic field. In contrast, the bacteriobot uses tumor targeting and the bacteria's own motility, and can exhibit self-targeting performance at solid tumors. However, because the propulsion forces of the bacteria are too small, it is very difficult for bacteriobot to track a tumor in a vessel with a large bloodstream. Therefore, we propose a hybrid actuated microrobot combined with electromagnetic actuation in large blood vessels with a macro range and bacterial actuation in small vessels with a micro range. In addition, the proposed microrobot consists of biodegradable and biocompatible microbeads in which the drugs and magnetic particles can be encapsulated; the bacteria can be attached to the surface of the microbeads and propel the microrobot. We carried out macro-manipulation of the hybrid actuated microrobot along a desired path through electromagnetic field control and the micro-manipulation of the hybrid actuated microrobot toward a chemical attractant through the chemotaxis of the bacteria. For the validation of the hybrid actuation of the microrobot, we fabricated a hydrogel microfluidic channel that can generate a chemical gradient. Finally, we evaluated the motility performance of the hybrid actuated microrobot in the hydrogel microfluidic channel. We expect

  11. How many diagnosis fields are needed to capture safety events in administrative data? Findings and recommendations from the WHO ICD-11 Topic Advisory Group on Quality and Safety

    PubMed Central

    Drösler, Saskia E.; Romano, Patrick S.; Sundararajan, Vijaya; Burnand, Bernard; Colin, Cyrille; Pincus, Harold; Ghali, William

    2014-01-01

    Objective As part of the WHO ICD-11 development initiative, the Topic Advisory Group on Quality and Safety explores meta-features of morbidity data sets, such as the optimal number of secondary diagnosis fields. Design The Health Care Quality Indicators Project of the Organization for Economic Co-Operation and Development collected Patient Safety Indicator (PSI) information from administrative hospital data of 19–20 countries in 2009 and 2011. We investigated whether three countries that expanded their data systems to include more secondary diagnosis fields showed increased PSI rates compared with six countries that did not. Furthermore, administrative hospital data from six of these countries and two American states, California (2011) and Florida (2010), were analysed for distributions of coded patient safety events across diagnosis fields. Results Among the participating countries, increasing the number of diagnosis fields was not associated with any overall increase in PSI rates. However, high proportions of PSI-related diagnoses appeared beyond the sixth secondary diagnosis field. The distribution of three PSI-related ICD codes was similar in California and Florida: 89–90% of central venous catheter infections and 97–99% of retained foreign bodies and accidental punctures or lacerations were captured within 15 secondary diagnosis fields. Conclusions Six to nine secondary diagnosis fields are inadequate for comparing complication rates using hospital administrative data; at least 15 (and perhaps more with ICD-11) are recommended to fully characterize clinical outcomes. Increasing the number of fields should improve the international and intra-national comparability of data for epidemiologic and health services research, utilization analyses and quality of care assessment. PMID:24334247

  12. Tests of the Dynamic Field Theory and The Spatial Precision Hypothesis: Capturing a Qualitative Developmental Transition in Spatial Working Memory

    ERIC Educational Resources Information Center

    Schutte, Anne R.; Spencer, John P.

    2009-01-01

    This study tested a dynamic field theory (DFT) of spatial working memory and an associated spatial precision hypothesis (SPH). Between 3 and 6 years of age, there is a qualitative shift in how children use reference axes to remember locations: 3-year-olds' spatial recall responses are biased toward reference axes after short memory delays, whereas…

  13. Capture of non-target flies (Diptera: Lauxaniidae, Chloropidae, Anthomyiidae) on traps baited with volatile chemicals in field crop habitats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Volatile chemicals increased trap catch of flies from the families Lauxaniidae [Homoneura bispina (Loew) and Camptoprosopella borealis Shewell], Chloropidae (Olcella sp.) and Anthomyiidae (Delia spp.) in field crops. With cotton rolls as dispensers, baiting with 2-phenylethanol increased catch of H...

  14. Magnetic-field-assisted photothermal therapy of cancer cells using Fe-doped carbon nanoparticles.

    PubMed

    Gu, Ling; Vardarajan, Vijaylakshmi; Koymen, Ali R; Mohanty, Samarendra K

    2012-01-01

    Photothermal therapy with assistance of nanoparticles offers a solution for the destruction of cancer cells without significant collateral damage to otherwise healthy cells. However, minimizing the required number of injected nanoparticles is a major challenge. Here, we introduce the use of magnetic carbon nanoparticles (MCNPs), localizing them in a desired region by applying an external magnetic-field, and irradiating the targeted cancer cells with a near-infrared laser beam. The MCNPs were prepared in benzene, using an electric plasma discharge, generated in the cavitation field of an ultrasonic horn. The CNPs were made ferromagnetic by use of Fe-electrodes to dope the CNPs, as confirmed by magnetometry. Transmission electron microscopy measurements showed the size distribution of these MCNPs to be in the range of 5 to 10 nm. For photothermal irradiation, a tunable continuous wave Ti: Sapphire laser beam was weakly focused on to the cell monolayer under an inverted fluorescence microscope. The response of different cell types to photothermal irradiation was investigated. Cell death in the presence of both MCNPs and laser beam was confirmed by morphological changes and propidium iodide fluorescence inclusion assay. The results of our study suggest that MCNP based photothermal therapy is a promising approach to remotely guide photothermal therapy.

  15. Magnetic-field-assisted photothermal therapy of cancer cells using Fe-doped carbon nanoparticles

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Vardarajan, Vijaylakshmi; Koymen, Ali R.; Mohanty, Samarendra K.

    2012-01-01

    Photothermal therapy with assistance of nanoparticles offers a solution for the destruction of cancer cells without significant collateral damage to otherwise healthy cells. However, minimizing the required number of injected nanoparticles is a major challenge. Here, we introduce the use of magnetic carbon nanoparticles (MCNPs), localizing them in a desired region by applying an external magnetic-field, and irradiating the targeted cancer cells with a near-infrared laser beam. The MCNPs were prepared in benzene, using an electric plasma discharge, generated in the cavitation field of an ultrasonic horn. The CNPs were made ferromagnetic by use of Fe-electrodes to dope the CNPs, as confirmed by magnetometry. Transmission electron microscopy measurements showed the size distribution of these MCNPs to be in the range of 5 to 10 nm. For photothermal irradiation, a tunable continuous wave Ti: Sapphire laser beam was weakly focused on to the cell monolayer under an inverted fluorescence microscope. The response of different cell types to photothermal irradiation was investigated. Cell death in the presence of both MCNPs and laser beam was confirmed by morphological changes and propidium iodide fluorescence inclusion assay. The results of our study suggest that MCNP based photothermal therapy is a promising approach to remotely guide photothermal therapy.

  16. A stochastic model simulating the capture of pathogenic micro-organisms by superparamagnetic particles in an isodynamic magnetic field.

    PubMed

    Rotariu, O; Strachan, N J C; Bădescu, V

    2004-09-01

    The method of immunomagnetic separation (IMS) has become an established technique to concentrate and separate animal cells, biologically active compounds and pathogenic micro-organisms from clinical, food and environmental matrices. One drawback of this technique is that the analysis is only possible for small sample volumes. We have developed a stochastic model that involves numerical simulations to optimize the process of concentration of pathogenic micro-organisms onto superparamagnetic carrier particles (SCPs) in a gradient magnetic field. Within the range of the system parameters varied in the simulations, optimal conditions favour larger particles with higher magnetite concentrations. The dependence on magnetic field intensity and gradient together with concentration of particles and micro-organisms was found to be less important for larger SCPs but these parameters can influence the values of the collision time for small particles. These results will be useful in aiding the design of apparatus for immunomagnetic separation from large volume samples.

  17. Fractionated Wide-Field Radiation Therapy Followed by Fractionated Local-Field Irradiation for Treating Widespread Painful Bone Metastasis

    SciTech Connect

    Ki, Yongkan; Kim, Wontaek; Nam, Jiho; Kim, Donghyun; Jeon, Hosang; Park, Dahl; Kim, Dongwon

    2011-01-01

    Purpose: Wide-field radiation therapy (WFRT) is an effective treatment for widespread bone metastasis. We evaluated local-field irradiation (LFI) after fractionated WFRT (f-WFRT) for treating the patients with multiple painful bone lesions. Methods and Materials: From 1998 to 2007, 32 patients with multiple bone metastases were treated with fractionated LFI (f-LFI) after f-WFRT. All patients initially received 15 Gy in 5 fractions to a wide field, followed by LFI (9-15 Gy in 3 Gy fractions). Response was assessed by evaluating the degree of pain relief using a visual analog scale before radiotherapy, after f-WFRT, and after f-LFI. Results: Fractionated LFI following f-WFRT yielded an overall relief rate of 93.8% and a complete relief rate of 43.8%. The rate of the appearance of new disease was 6.3% for the patients with complete relief, 20.5% for the patients with a partial relief, and 50% for the patients with no relief. Conclusion: Fractionated LFI after f-WFRT is a well-tolerated and effective treatment for multiple metastatic bone disease.

  18. 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.

  19. 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

  20. 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

  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. Laser capture.

    PubMed

    Potter, S Steven; Brunskill, Eric W

    2012-01-01

    This chapter describes detailed methods used for laser capture microdissection (LCM) of discrete subpopulations of cells. Topics covered include preparing tissue blocks, cryostat sectioning, processing slides, performing the LCM, and purification of RNA from LCM samples. Notes describe the fine points of each operation, which can often mean the difference between success and failure. PMID:22639264

  3. Capturing Movement

    ERIC Educational Resources Information Center

    Lord, Lynda

    2007-01-01

    The idea for the art lesson presented in this article grew out of watching the lively actions of fourth grade students. Since drawing is the author's first love, she is always looking for new ways to teach it. This time, instead of setting up a still life, she decided to teach students how to capture their actions on paper. (Contains 5 online…

  4. Monte Carlo calculations for absolute dosimetry to determine machine outputs for proton therapy fields

    PubMed Central

    Paganetti, Harald

    2008-01-01

    The prescribed dose in radiation therapy has to be converted into machine monitor units for patient treatment. This is done routinely for each spread-out Bragg peak (SOBP) field either by calibration measurements, by using analytical algorithms or by relying on empirical data. At the Northeast Proton Therapy Center, a monitor unit corresponds to a fixed amount of charge collected in a segmented transmission ionization chamber inside the treatment head. The goal of this work was to use a detailed Monte Carlo model of the treatment head to calculate the dose delivered to the patient as a function of ionization chamber reading, i.e. to yield absolute dose in patients in terms of machine monitor units. The results show excellent agreement with measurements. For 50 SOBP fields considered in this study, the mean absolute difference between the experimental and the calculated value is 1.5%, where ~50% of the fields agree within 1%. This is within the uncertainties of the data. The Monte Carlo method has advantages over analytical algorithms because it takes into account scattered and secondary radiation, does not rely on empirical parameters, and provides a tool to study the influence of parts of the treatment head on the ionization chamber reading. Compared to experimental methods the Monte Carlo method has the advantage of being able to verify the dose in the patient geometry. PMID:16723767

  5. Gene therapy for hemoglobinopathies: the state of the field and the future.

    PubMed

    Chandrakasan, Shanmuganathan; Malik, Punam

    2014-04-01

    After nearly two decades of struggle, gene therapy for hemoglobinopathies using vectors carrying β or γ-globin gene has finally reached the clinical doorsteps. This was made possible by advances made in our understanding of critical regulatory elements required for high level of globin gene expression and improved gene transfer vectors and methodologies. Development of gene editing technologies and reprogramming somatic cells for regenerative medicine holds the promise of genetic correction of hemoglobinopathies in the future. This article will review the state of the field and the upcoming technologies that will allow genetic therapeutic correction of hemoglobinopathies.

  6. Blood meal identification and parasite detection in laboratory-fed and field-captured Lutzomyia longipalpis by PCR using FTA databasing paper

    PubMed Central

    Sant’Anna, Mauricio R.V.; Jones, Nathaniel G.; Hindley, Jonathan A.; Mendes-Sousa, Antonio F.; Dillon, Rod J.; Cavalcante, Reginaldo R.; Alexander, Bruce; Bates, Paul A.

    2008-01-01

    The phlebotomine sand fly Lutzomyia longipalpis takes blood from a variety of wild and domestic animals and transmits Leishmania (Leishmania) infantum chagasi, etiological agent of American visceral leishmaniasis. Blood meal identification in sand flies has depended largely on serological methods but a new protocol described here uses filter-based technology to stabilise and store blood meal DNA, allowing subsequent PCR identification of blood meal sources, as well as parasite detection, in blood-fed sand flies. This technique revealed that 53.6% of field-collected sand flies captured in the back yards of houses in Teresina (Brazil) had fed on chickens. The potential applications of this technique in epidemiological studies and strategic planning for leishmaniasis control programmes are discussed. PMID:18606150

  7. Tidal capture formation of low-mass X-ray binaries from wide binaries in the field

    NASA Astrophysics Data System (ADS)

    Michaely, Erez; Perets, Hagai B.

    2016-06-01

    We present a dynamical formation scenario for low mass X-ray binaries (LMXBs) in the field, focusing on black hole (BH) LMXBs. In this formation channel, LMXBs are formed from wide binaries (>1000 au) with a BH component and a stellar companion. The wide binary is perturbed by fly-bys of field stars, its orbit random walks, until driven into a sufficiently eccentric orbit such that the binary components tidally interact and the binary evolves to become a short period binary, which eventually evolves into an LMXB. We consider several models for the formation and survival of such wide binaries, and calculate the LMXB formation rates for each model. We find that models where BHs form through direct collapse with no/little natal kicks can give rise to high formation rates comparable with those inferred from observations. This formation scenario had several observational signatures: (1) the number density of LMXBs generally follows the background stellar density, beside the densest regions, where the dependence is stronger, (2) the mass function of the BH stellar companion should be comparable to the mass function of the background stellar population, likely peaking at 0.4-0.6 M⊙, and (3) the LMXBs orbit should not correlate with the spin of the BH. These aspects generally differ from the expectations from previously suggested LMXB formation models following common envelope binary stellar evolution. We note that neutron star LMXBs can similarly form from wide binaries, but their formation rate through this channel is likely significantly smaller due to their much higher natal kicks.

  8. Tests of the Dynamic Field Theory and the Spatial Precision Hypothesis: Capturing a Qualitative Developmental Transition in Spatial Working Memory

    PubMed Central

    Schutte, Anne R.; Spencer, John P.

    2009-01-01

    This study tested a dynamic field theory (DFT) of spatial working memory and an associated spatial precision hypothesis (SPH). Between three and six years of age there is a qualitative shift in how children use reference axes to remember locations: 3-year-olds’ spatial recall responses are biased toward reference axes after short memory delays, whereas 6-year-olds’ responses are biased away from reference axes. According to the DFT and the SPH, quantitative improvements over development in the precision of excitatory and inhibitory working memory processes lead to this qualitative shift. Simulations of the DFT in Experiment 1 predict that improvements in precision should cause the spatial range of targets attracted toward a reference axis to narrow gradually over development with repulsion emerging and gradually increasing until responses to most targets show biases away from the axis. Results from Experiment 2 with 3- to 5-year-olds support these predictions. Simulations of the DFT in Experiment 3 quantitatively fit the empirical results and offer insights into the neural processes underlying this developmental change. PMID:19968430

  9. Optimization of pulsed electromagnetic field therapy for management of arthritis in rats.

    PubMed

    Kumar, Venkatachalam Senthil; Kumar, Dilly Ashok; Kalaivani, Kalyanasundaram; Gangadharan, Akkalayi Chandrapuram; Raju, K V S Narayana; Thejomoorthy, Pammi; Manohar, Bhakthavatchalam Murali; Puvanakrishnan, Rengarajulu

    2005-09-01

    Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 mug/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and beta-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau-Braunbeck coil system. A magnetic field of 5 Hz x 4 muT x 90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of beta-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans.

  10. Low-level laser therapy on bone repair: is there any effect outside the irradiated field?

    PubMed

    Batista, Jonas Dantas; Sargenti-Neto, Sérgio; Dechichi, Paula; Rocha, Flaviana Soares; Pagnoncelli, Rogério Miranda

    2015-07-01

    The biological effects of local therapy with laser on bone repair have been well demonstrated; however, this possible effect on bone repair outside the irradiated field has not been evaluated. The aim of this study was to investigate the effect of low-level laser therapy (LLLT) (λ = 830 nm) on repair of surgical bone defects outside the irradiated field, in rats. Sixty Wistar rats were submitted to osteotomy on the left femur and randomly separated into four groups (n = 15): group I, control, bone defect only; group II, laser applied on the right femur (distant dose); group III, laser applied locally on the bone defect and also on the right femur (local and distant doses); and group IV, laser applied locally on the left femur (local dose). Laser groups received applications within a 48-h interval in one point per session of density energy (DE) = 210 J/cm(2), P = 50 mW, t = 120 s, and beam diameter of 0.028 cm. Five animals of each group were euthanized 7, 15, and 21 days after surgery. Histologic analysis in all groups showed new bone formation in the region of interest (ROI) at 7 days. After 15 days, bone remodeling with a decrease of bone neoformation in the marrow area was observed in all groups. After 21 days, advanced bone remodeling with new bone mostly located in the cortical area was observed. The histomorphometric analysis showed at 7 days a significant increase of bone formation in groups III and IV compared to groups I and II. At days 15 and 21, histomorphometric analysis showed no significant differences between them. Laser therapy presented a positive local biostimulative effect in the early stage of bone healing, but the LLLT effect was not observed a long distance from the evaluated area.

  11. 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

  12. US Spacesuit Knowledge Capture

    NASA Technical Reports Server (NTRS)

    Chullen, Cinda; Thomas, Ken; McMann, Joe; Dolan, Kristi; Bitterly, Rose; Lewis, Cathleen

    2011-01-01

    The ability to learn from both the mistakes and successes of the past is vital to assuring success in the future. Due to the close physical interaction between spacesuit systems and human beings as users, spacesuit technology and usage lends itself rather uniquely to the benefits realized from the skillful organization of historical information; its dissemination; the collection and identification of artifacts; and the education of those in the field. The National Aeronautics and Space Administration (NASA), other organizations and individuals have been performing United States (U.S.) Spacesuit Knowledge Capture since the beginning of space exploration. Avenues used to capture the knowledge have included publication of reports; conference presentations; specialized seminars; and classes usually given by veterans in the field. More recently the effort has been more concentrated and formalized whereby a new avenue of spacesuit knowledge capture has been added to the archives in which videotaping occurs engaging both current and retired specialists in the field presenting technical scope specifically for education and preservation of knowledge. With video archiving, all these avenues of learning can now be brought to life with the real experts presenting their wealth of knowledge on screen for future learners to enjoy. Scope and topics of U.S. spacesuit knowledge capture have included lessons learned in spacesuit technology, experience from the Gemini, Apollo, Skylab and Shuttle programs, hardware certification, design, development and other program components, spacesuit evolution and experience, failure analysis and resolution, and aspects of program management. Concurrently, U.S. spacesuit knowledge capture activities have progressed to a level where NASA, the National Air and Space Museum (NASM), Hamilton Sundstrand (HS) and the spacesuit community are now working together to provide a comprehensive closed-looped spacesuit knowledge capture system which includes

  13. Electric field characteristics of electroconvulsive therapy with individualized current amplitude: a preclinical study.

    PubMed

    Lee, Won Hee; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

    2013-01-01

    This study examines the characteristics of the electric field induced in the brain by electroconvulsive therapy (ECT) with individualized current amplitude. The electric field induced by bilateral (BL), bifrontal (BF), right unilateral (RUL), and frontomedial (FM) ECT electrode configurations was computed in anatomically realistic finite element models of four nonhuman primates (NHPs). We generated maps of the electric field strength relative to an empirical neural activation threshold, and determined the stimulation strength and focality at fixed current amplitude and at individualized current amplitudes corresponding to seizure threshold (ST) measured in the anesthetized NHPs. The results show less variation in brain volume stimulated above threshold with individualized current amplitudes (16-36%) compared to fixed current amplitude (30-62%). Further, the stimulated brain volume at amplitude-titrated ST is substantially lower than that for ECT with conventional fixed current amplitudes. Thus individualizing the ECT stimulus current could compensate for individual anatomical variability and result in more focal and uniform electric field exposure across different subjects compared to the standard clinical practice of using high, fixed current for all patients.

  14. Local and Global Impacts of Carbon Capture and Storage Combined with Enhanced Oil Recovery in Four Depleted Oil Fields, Kern County, California

    NASA Astrophysics Data System (ADS)

    Gillespie, J.; Jordan, P. D.; Goodell, J. A.; Harrington, K.; Jameson, S.

    2015-12-01

    Depleted oil reservoirs are attractive targets for geologic carbon storage (GCS) because they possess proven trapping mechanisms and large amounts of data pertaining to production and reservoir geometry. In addition, CO2 enhanced oil recovery (EOR) can improve recovery of the remaining oil at recovery factors of 6 to 20% of original oil in place in appropriate reservoirs. CO2 EOR increases the attractiveness of depleted oil and gas reservoirs as a starting point for CCS because the CO2 becomes a commodity that can be purchased by field operators for EOR purposes thereby offsetting the costs of CO2 capture at the power plant. In California, Kern County contains the largest oil reservoirs and produces 76% of California's oil. Most of the production at depths suitable for CCS combined with CO2 EOR comes from three reservoirs: the Vedder and Temblor formations and the Stevens Sandstone of the Monterey Formation. These formations were evaluated for GCS and CO2 EOR potential at the North and South Coles Levee (Stevens Sandstone), Greeley (Vedder) and McKittrick (Temblor) fields. CO2 EOR could be expected to produce an additional 150 million bbls of oil. The total storage space created by pre- and post-EOR fluid production for all three reservoirs is approximately 104 million metric tons (MMT). Large fixed sources in California produce 156 MMT/yr of CO2, and sources in Kern County produce 26 MMT/yr (WESTCARB, 2012). Therefore, the fields could store about four years of local large fixed source emissions and about two thirds of statewide emissions. However, from a global perspective, burning the additional oil produced by CO2 EOR would generate an additional 65 MMT of CO2 if not captured. This would result in a net reduction of greenhouse gas of only 39 MMT rather than the full 104 MMT. If the water produced along with the oil recovered during CO2 EOR operations is not reinjected into the reservoir, the storage space could be much higher.

  15. Fitting a Structured Juvenile-Adult Model for Green Tree Frogs to Population Estimates from Capture-Mark-Recapture Field Data

    USGS Publications Warehouse

    Ackleh, A.S.; Carter, J.; Deng, K.; Huang, Q.; Pal, N.; Yang, X.

    2012-01-01

    We derive point and interval estimates for an urban population of green tree frogs (Hyla cinerea) from capture-mark-recapture field data obtained during the years 2006-2009. We present an infinite-dimensional least-squares approach which compares a mathematical population model to the statistical population estimates obtained from the field data. The model is composed of nonlinear first-order hyperbolic equations describing the dynamics of the amphibian population where individuals are divided into juveniles (tadpoles) and adults (frogs). To solve the least-squares problem, an explicit finite difference approximation is developed. Convergence results for the computed parameters are presented. Parameter estimates for the vital rates of juveniles and adults are obtained, and standard deviations for these estimates are computed. Numerical results for the model sensitivity with respect to these parameters are given. Finally, the above-mentioned parameter estimates are used to illustrate the long-time behavior of the population under investigation. ?? 2011 Society for Mathematical Biology.

  16. Optimal moderator materials at various proton energies considering photon dose rate after irradiation for an accelerator-driven ⁹Be(p, n) boron neutron capture therapy neutron source.

    PubMed

    Hashimoto, Y; Hiraga, F; Kiyanagi, Y

    2015-12-01

    We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation. PMID:26272165

  17. Optimal moderator materials at various proton energies considering photon dose rate after irradiation for an accelerator-driven ⁹Be(p, n) boron neutron capture therapy neutron source.

    PubMed

    Hashimoto, Y; Hiraga, F; Kiyanagi, Y

    2015-12-01

    We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation.

  18. Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma

    PubMed Central

    Omar, Ayman I.

    2014-01-01

    A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA approved in April 2011 for the treatment of patients 22 years or older with rGBM. The device delivers alternating electric fields and is programmed to ensure maximal tumor cell kill1. Glioblastoma is the most common type of glioma and has an estimated incidence of approximately 10,000 new cases per year in the United States alone2. This tumor is particularly resistant to treatment and is uniformly fatal especially in the recurrent setting3-5. Prior to the approval of the TTF System, the only FDA approved treatment for rGBM was bevacizumab6. Bevacizumab is a humanized monoclonal antibody targeted against the vascular endothelial growth factor (VEGF) protein that drives tumor angiogenesis7. By blocking the VEGF pathway, bevacizumab can result in a significant radiographic response (pseudoresponse), improve progression free survival and reduce corticosteroid requirements in rGBM patients8,9. Bevacizumab however failed to prolong overall survival in a recent phase III trial26. A pivotal phase III trial (EF-11) demonstrated comparable overall survival between physicians’ choice chemotherapy and TTF Therapy but better quality of life were observed in the TTF arm10. There is currently an unmet need to develop novel approaches designed to prolong overall survival and/or improve quality of life in this unfortunate patient population. One appealing approach would be to combine the two currently approved treatment modalities namely bevacizumab and TTF Therapy. These two treatments are currently approved as monotherapy11,12, but their combination has never been evaluated in a clinical trial. We have developed an approach for combining those two treatment modalities and treated 2 rGBM patients. Here we describe a detailed methodology outlining this novel treatment protocol and present representative data from one of the

  19. Static Magnetic Field Therapy for Carpal Tunnel Syndrome: A Feasibility Study

    PubMed Central

    Colbert, Agatha P.; Markov, Marko S.; Carlson, Nels; Gregory, William L.; Carlson, Hans; Elmer, Patricia J.

    2010-01-01

    Objectives To assess the feasibility of conducting trials of static magnetic field (SMF) therapy for carpal tunnel syndrome (CTS), to collect preliminary data on the effectiveness of two SMF dosages and to explore the influence of a SMF on median nerve conduction. Design Randomized, double blind, sham controlled trial with 6-week intervention and 12-week follow-up. Setting University hospital outpatient clinics Participants Women and men (N=60), ages 21–65, with electrophysiologically-confirmed CTS diagnosis, recruited from the general population. Interventions Participants wore nightly either neodymium magnets that delivered either 15 or 45mTesla (mT) to the contents of the carpal canal, or a non-magnetic disk. Main Outcome Measures Symptom Severity Scale (SSS) and Function Severity Scale (FSS) of the Boston Carpal Tunnel Questionnaire (BCTQ) and 4 median nerve parameters: sensory distal latency, sensory nerve action potential amplitude, motor distal latency and compound motor action potential amplitude). Results 58 of 60 randomized participants completed the study. There were no significant between-group differences for change in the primary endpoint SSS or for FSS or median nerve conduction parameters. For the SSS and the FSS each group showed a reduction at 6-weeks indicating improvement in symptoms. Conclusions This study demonstrated the feasibility and safety of testing SMF therapy for CTS. There were no between-group differences observed for the BCTQ or median nerve parameters following 6 weeks of SMF therapy. Significant within-group, symptomatic improvements of the same magnitude were experienced by participants in both active and sham magnet groups. Future studies are needed to optimize SMF dosimetry and resolve issues related to the use of sham controls in SMF trials. PMID:20599049

  20. Tumor treating field therapy in combination with bevacizumab for the treatment of recurrent glioblastoma.

    PubMed

    Omar, Ayman I

    2014-10-27

    A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA approved in April 2011 for the treatment of patients 22 years or older with rGBM. The device delivers alternating electric fields and is programmed to ensure maximal tumor cell kill. Glioblastoma is the most common type of glioma and has an estimated incidence of approximately 10,000 new cases per year in the United States alone. This tumor is particularly resistant to treatment and is uniformly fatal especially in the recurrent setting. Prior to the approval of the TTF System, the only FDA approved treatment for rGBM was bevacizumab. Bevacizumab is a humanized monoclonal antibody targeted against the vascular endothelial growth factor (VEGF) protein that drives tumor angiogenesis. By blocking the VEGF pathway, bevacizumab can result in a significant radiographic response (pseudoresponse), improve progression free survival and reduce corticosteroid requirements in rGBM patients. Bevacizumab however failed to prolong overall survival in a recent phase III trial. A pivotal phase III trial (EF-11) demonstrated comparable overall survival between physicians' choice chemotherapy and TTF Therapy but better quality of life were observed in the TTF arm. There is currently an unmet need to develop novel approaches designed to prolong overall survival and/or improve quality of life in this unfortunate patient population. One appealing approach would be to combine the two currently approved treatment modalities namely bevacizumab and TTF Therapy. These two treatments are currently approved as monotherapy, but their combination has never been evaluated in a clinical trial. We have developed an approach for combining those two treatment modalities and treated 2 rGBM patients. Here we describe a detailed methodology outlining this novel treatment protocol and present representative data from one of the treated patients.

  1. Effect of organ size and position on out-of-field dose distributions during radiation therapy

    NASA Astrophysics Data System (ADS)

    Scarboro, Sarah B.; Stovall, Marilyn; White, Allen; Smith, Susan A.; Yaldo, Derek; Kry, Stephen F.; Howell, Rebecca M.

    2010-12-01

    Mantle field irradiation has historically been the standard radiation treatment for Hodgkin lymphoma. It involves treating large regions of the chest and neck with high doses of radiation (up to 30 Gy). Previous epidemiological studies on the incidence of second malignancies following radiation therapy for Hodgkin lymphoma have revealed an increased incidence of second tumors in various organs, including lung, breast, thyroid and digestive tract. Multiple other studies, including the Surveillance, Epidemiology and End Results, indicated an increased incidence in digestive tract including stomach cancers following mantle field radiotherapy. Assessment of stomach dose is challenging because the stomach is outside the treatment field but very near the treatment border where there are steep dose gradients. In addition, the stomach can vary greatly in size and position. We sought to evaluate the dosimetric impact of the size and variable position of the stomach relative to the field border for a typical Hodgkin lymphoma mantle field irradiation. The mean stomach dose was measured using thermoluminescent dosimetry for nine variations in stomach size and position. The mean doses to the nine stomach variations ranged from 0.43 to 0.83 Gy when 30 Gy was delivered to the treatment isocenter. Statistical analyses indicated that there were no significant differences in the mean stomach dose when the stomach was symmetrically expanded up to 3 cm or shifted laterally (medial, anterior or posterior shifts) by up to 3 cm. There was, however, a significant (P > 0.01) difference in the mean dose when the stomach was shifted superiorly or inferiorly by >=2.5 cm.

  2. Effect of organ size and position on out-of-field dose distributions during radiation therapy.

    PubMed

    Scarboro, Sarah B; Stovall, Marilyn; White, Allen; Smith, Susan A; Yaldo, Derek; Kry, Stephen F; Howell, Rebecca M

    2010-12-01

    Mantle field irradiation has historically been the standard radiation treatment for Hodgkin lymphoma. It involves treating large regions of the chest and neck with high doses of radiation (up to 30 Gy). Previous epidemiological studies on the incidence of second malignancies following radiation therapy for Hodgkin lymphoma have revealed an increased incidence of second tumors in various organs, including lung, breast, thyroid and digestive tract. Multiple other studies, including the Surveillance, Epidemiology and End Results, indicated an increased incidence in digestive tract including stomach cancers following mantle field radiotherapy. Assessment of stomach dose is challenging because the stomach is outside the treatment field but very near the treatment border where there are steep dose gradients. In addition, the stomach can vary greatly in size and position. We sought to evaluate the dosimetric impact of the size and variable position of the stomach relative to the field border for a typical Hodgkin lymphoma mantle field irradiation. The mean stomach dose was measured using thermoluminescent dosimetry for nine variations in stomach size and position. The mean doses to the nine stomach variations ranged from 0.43 to 0.83 Gy when 30 Gy was delivered to the treatment isocenter. Statistical analyses indicated that there were no significant differences in the mean stomach dose when the stomach was symmetrically expanded up to 3 cm or shifted laterally (medial, anterior or posterior shifts) by up to 3 cm. There was, however, a significant (P > 0.01) difference in the mean dose when the stomach was shifted superiorly or inferiorly by ≥2.5 cm.

  3. Acoustic field characterization of the Duolith: measurements and modeling of a clinical shock wave therapy device.

    PubMed

    Perez, Camilo; Chen, Hong; Matula, Thomas J; Karzova, Maria; Khokhlova, Vera A

    2013-08-01

    Extracorporeal shock wave therapy (ESWT) uses acoustic pulses to treat certain musculoskeletal disorders. In this paper the acoustic field of a clinical portable ESWT device (Duolith SD1) was characterized. Field mapping was performed in water for two different standoffs of the electromagnetic head (15 or 30 mm) using a fiber optic probe hydrophone. Peak positive pressures at the focus ranged from 2 to 45 MPa, while peak negative pressures ranged from -2 to -11 MPa. Pulse rise times ranged from 8 to 500 ns; shock formation did not occur for any machine settings. The maximum standard deviation in peak pressure at the focus was 1.2%, indicating that the Duolith SD1 generates stable pulses. The results compare qualitatively, but not quantitatively with manufacturer specifications. Simulations were carried out for the short standoff by matching a Khokhlov-Zabolotskaya-Kuznetzov equation to the measured field at a plane near the source, and then propagating the wave outward. The results of modeling agree well with experimental data. The model was used to analyze the spatial structure of the peak pressures. Predictions from the model suggest that a true shock wave could be obtained in water if the initial pressure output of the device were doubled.

  4. Normal-conducting scaling fixed field alternating gradient accelerator for proton therapy

    NASA Astrophysics Data System (ADS)

    Garland, J. M.; Appleby, R. B.; Owen, H.; Tygier, S.

    2015-09-01

    In this paper we present a new lattice design for a 30-350 MeV scaling fixed-field alternating gradient accelerator for proton therapy and tomography—NORMA (NOrmal-conducting Racetrack Medical Accelerator). The energy range allows the realization of proton computed tomography and utilizes normal conducting magnets in both a conventional circular ring option and a novel racetrack configuration, both designed using advanced optimization algorithms we have developed in pyzgoubi. Both configurations consist of ten focusing-defocusing-focusing triplet cells and operate in the second stability region of Hills equation. The ring configuration has a circumference of 60 m, a peak magnetic field seen by the beam of <1.6 T , a maximum horizontal orbit excursion of 44 cm and a dynamic aperture of 68 mm mrad—determined using a novel dynamic aperture (DA) calculation technique. The racetrack alternative is realized by adding magnet-free drift space in between cells at two opposing points in the ring, to facilitate injection and extraction. Our racetrack design has a total magnet-free straight lengths of 4.9 m, a circumference of 71 m, a peak magnetic field seen by the beam of <1.74 T , a maximum horizontal orbit excursion of 50 cm and a DA of 58 mm mrad. A transverse magnet misalignment model is also presented for the ring and racetrack configurations where the DA remains above 40 mm mrad for randomly misaligned error distributions with a standard deviation up to 100 μ m .

  5. Acoustic field characterization of the Duolith: Measurements and modeling of a clinical shock wave therapy device

    PubMed Central

    Perez, Camilo; Chen, Hong; Matula, Thomas J.; Karzova, Maria; Khokhlova, Vera A.

    2013-01-01

    Extracorporeal shock wave therapy (ESWT) uses acoustic pulses to treat certain musculoskeletal disorders. In this paper the acoustic field of a clinical portable ESWT device (Duolith SD1) was characterized. Field mapping was performed in water for two different standoffs of the electromagnetic head (15 or 30 mm) using a fiber optic probe hydrophone. Peak positive pressures at the focus ranged from 2 to 45 MPa, while peak negative pressures ranged from −2 to −11 MPa. Pulse rise times ranged from 8 to 500 ns; shock formation did not occur for any machine settings. The maximum standard deviation in peak pressure at the focus was 1.2%, indicating that the Duolith SD1 generates stable pulses. The results compare qualitatively, but not quantitatively with manufacturer specifications. Simulations were carried out for the short standoff by matching a Khokhlov-Zabolotskaya-Kuznetzov equation to the measured field at a plane near the source, and then propagating the wave outward. The results of modeling agree well with experimental data. The model was used to analyze the spatial structure of the peak pressures. Predictions from the model suggest that a true shock wave could be obtained in water if the initial pressure output of the device were doubled. PMID:23927207

  6. On measuring depth-dose distribution of range-modulated proton therapy fields

    SciTech Connect

    Lu, H.-M.

    2006-07-15

    Depth-dose profile measurements are frequently performed for the characterization of spread-out Bragg peak treatment fields in proton therapy. The measured distribution often contains a significant amount of noise with a persistent pattern. As a result, substantial smoothing has to be applied which can alter a measurement. We explored the origin of the observed noise by closely examining the sampling process in the scanning algorithm. We will show that the time characteristics of the signal in the range-modulated proton therapy beams differ significantly from those in the photon beams, and as a result the measurement error is very sensitive to the sampling duration. The observed noise results mainly from inappropriate choices for this value, rather than from the dose distribution itself. Increasing the value arbitrarily may actually increase the noise magnitude. We will demonstrate that with an optimal value for the sampling duration and its accurate control, the noise magnitude can be reduced significantly, without increasing the measurement time.

  7. Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Hu, Yue; Yang, Yamin; Wang, Hongjun; Du, Henry

    2013-02-01

    Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

  8. Magnetic field activated drug release system based on magnetic PLGA microspheres for chemo-thermal therapy.

    PubMed

    Fang, Kun; Song, Lina; Gu, Zhuxiao; Yang, Fang; Zhang, Yu; Gu, Ning

    2015-12-01

    Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3 wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30 min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.

  9. An Almost Linear Time Algorithm for Field Splitting in Radiation Therapy.

    PubMed

    Wu, Xiaodong; Dou, Xin; Bayouth, John E; Buatti, John M

    2013-08-01

    In this paper, we study an interesting geometric partition problem, called optimal field splitting, which arises in Intensity-Modulated Radiation Therapy (IMRT). In current clinical practice, a multi-leaf collimator (MLC) with a maximum leaf spread constraint is used to deliver the prescribed intensity maps (IMs). However, the maximum leaf spread of an MLC may require to split a large intensity map into several overlapping sub-IMs with each being delivered separately. We develop a close-to-linear time algorithm for solving the field splitting problem while minimizing the total complexity of the resulting sub-IMs, thus improving the treatment delivery efficiency. Meanwhile, our algorithm strives to minimize the maximum beam-on time of those sub-IMs. Our basic idea is to formulate the field splitting problem as computing a shortest path in a directed acyclic graph, which expresses a special "layered" structure. The edge weights of the graph satisfy the Monge property, which enables us to solve this shortest path problem by examining only a small portion of the graph, yielding a close-to-linear time algorithm. To minimize the maximum beam-on time of the resulting sub-IMs, we consider an interesting min-max slope path problem in a monotone polygon which is solvable in linear time. The min-max slope path problem may be of interest in its own right. Experimental results based on real medical data and computer generated IMs showed that our new algorithm runs fast and produces high quality field splitting results. PMID:24999294

  10. Estimating population size for Capercaillie (Tetrao urogallus L.) with spatial capture-recapture models based on genotypes from one field sample

    USGS Publications Warehouse

    Mollet, Pierre; Kery, Marc; Gardner, Beth; Pasinelli, Gilberto; Royle, Andy

    2015-01-01

    We conducted a survey of an endangered and cryptic forest grouse, the capercaillie Tetrao urogallus, based on droppings collected on two sampling occasions in eight forest fragments in central Switzerland in early spring 2009. We used genetic analyses to sex and individually identify birds. We estimated sex-dependent detection probabilities and population size using a modern spatial capture-recapture (SCR) model for the data from pooled surveys. A total of 127 capercaillie genotypes were identified (77 males, 46 females, and 4 of unknown sex). The SCR model yielded atotal population size estimate (posterior mean) of 137.3 capercaillies (posterior sd 4.2, 95% CRI 130–147). The observed sex ratio was skewed towards males (0.63). The posterior mean of the sex ratio under the SCR model was 0.58 (posterior sd 0.02, 95% CRI 0.54–0.61), suggesting a male-biased sex ratio in our study area. A subsampling simulation study indicated that a reduced sampling effort representing 75% of the actual detections would still yield practically acceptable estimates of total size and sex ratio in our population. Hence, field work and financial effort could be reduced without compromising accuracy when the SCR model is used to estimate key population parameters of cryptic species.

  11. Repeatability of three-dimensional thorax and pelvis kinematics in the golf swing measured using a field-based motion capture system.

    PubMed

    Evans, Kerrie; Horan, Sean A; Neal, Robert J; Barrett, Rod S; Mills, Peter M

    2012-06-01

    Field-based methods of evaluating three-dimensional (3D) swing kinematics offer coaches and researchers the opportunity to assess golfers in context-specific environments. The purpose of this study was to establish the inter-trial, between-tester, between-location, and between-day repeatability of thorax and pelvis kinematics during the downswing using an electromagnetic motion capture system. Two experienced testers measured swing kinematics in 20 golfers (handicap < or =14 strokes) on consecutive days in an indoor and outdoor location. Participants performed five swings with each of two clubs (five-iron and driver) at each test condition. Repeatability of 3D kinematic data was evaluated by computing the coefficient of multiple determination (CMD) and the systematic error (SE). With the exception of pelvis forward bend for between-day and between-tester conditions, CMDs exceeded 0.854 for all variables, indicating high levels of overall waveform repeatability across conditions. When repeatability was compared across conditions using MANOVA, the lowest CMDs and highest SEs were found for the between-tester and between-day conditions. The highest CMDs were for the inter-trial and between-location conditions. The absence of significant differences in CMDs between these two conditions supports this method of analysing pelvis and thorax kinematics in different environmental settings without unduly affecting repeatability. PMID:22900406

  12. Estimating Population Size for Capercaillie (Tetrao urogallus L.) with Spatial Capture-Recapture Models Based on Genotypes from One Field Sample

    PubMed Central

    Mollet, Pierre; Kéry, Marc; Gardner, Beth; Pasinelli, Gilberto; Royle, J. Andrew

    2015-01-01

    We conducted a survey of an endangered and cryptic forest grouse, the capercaillie Tetrao urogallus, based on droppings collected on two sampling occasions in eight forest fragments in central Switzerland in early spring 2009. We used genetic analyses to sex and individually identify birds. We estimated sex-dependent detection probabilities and population size using a modern spatial capture-recapture (SCR) model for the data from pooled surveys. A total of 127 capercaillie genotypes were identified (77 males, 46 females, and 4 of unknown sex). The SCR model yielded atotal population size estimate (posterior mean) of 137.3 capercaillies (posterior sd 4.2, 95% CRI 130–147). The observed sex ratio was skewed towards males (0.63). The posterior mean of the sex ratio under the SCR model was 0.58 (posterior sd 0.02, 95% CRI 0.54–0.61), suggesting a male-biased sex ratio in our study area. A subsampling simulation study indicated that a reduced sampling effort representing 75% of the actual detections would still yield practically acceptable estimates of total size and sex ratio in our population. Hence, field work and financial effort could be reduced without compromising accuracy when the SCR model is used to estimate key population parameters of cryptic species. PMID:26087321

  13. Pulsed radiofrequency electromagnetic field therapy: a potential novel treatment of plantar fasciitis.

    PubMed

    Brook, Joel; Dauphinee, Damien M; Korpinen, Jaryl; Rawe, Ian M

    2012-01-01

    Plantar fasciitis is a common cause of heel pain, and although treatments are usually conservative, they can take up to 2 years to achieve resolution. A double-blind, multicenter, randomized, placebo-controlled study was used to evaluate a small, wearable, extended-use pulsed radiofrequency electromagnetic field (PRFE) device as a treatment of plantar fasciitis. A total of 70 subjects diagnosed with plantar fasciitis were enrolled in the present study. The subjects were randomly assigned a placebo or active PRFE device. The subjects were instructed to wear the PRFE device overnight, record their morning and evening pain using a 0- to 10-point visual analog scale (VAS), and log any medication use. The primary outcome measure for the present study was morning pain, a hallmark of plantar fasciitis. The study group using the active PRFE device showed progressive decline in morning pain. The day 7 AM-VAS score was 40% lower than the day 1 AM-VAS score. The control group, in comparison, showed a 7% decline. A significantly different decline was demonstrated between the 2 groups (p = .03). The PM-VAS scores declined by 30% in the study group and 19% in the control group, although the difference was not significant. Medication use in the study group also showed a trend downward, but the use in the control group remained consistent with the day 1 levels. PRFE therapy worn on a nightly basis appears to offer a simple, drug-free, noninvasive therapy to reduce the pain associated with plantar fasciitis.

  14. Music Therapy as a Caring Intervention: Swedish Musicians Learning a New Professional Field

    ERIC Educational Resources Information Center

    Petersson, Gunnar; Nystrom, Maria

    2011-01-01

    The question of competence in providing music therapy has rarely been the focus of interest in empirical research, as most music therapy research aims at measuring outcomes. Therefore, the aim of this study is to analyse and describe musicians' learning processes when they study music therapy as a caring intervention. An initial presumption is…

  15. Dosimetric effects on small-field beam-modeling for stereotactic body radiation therapy

    NASA Astrophysics Data System (ADS)

    Cho, Woong; Kim, Suzy; Kim, Jung-In; Wu, Hong-Gyun; Jung, Joo-Young; Kim, Min-Joo; Suh, Tae-Suk; Kim, Jin-Young; Kim, Jong Won

    2015-02-01

    The treatment planning of stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) requires high accuracy of dosimetric data for small radiation fields. The dosimetric effects on the beam-modeling process of a treatment planning system (TPS) were investigated using different measured small-field data sets. We performed small-field dosimetry with three detectors: a CC13 ion chamber, a CC01 ion chamber, and an edge detector. Percentage depth doses (PDDs) and dose profiles for field sizes given by 3 × 3 cm2, 2 × 2 cm2, and 1 × 1 cm2 were obtained for 6 MV and 15 MV photon beams. Each measured data set was used as data input for a TPS, in which a beam-modeling process was implemented using the collapsed cone convolution (CCC) algorithm for dose calculation. The measured data were used to generate six beam-models based on each combination of detector type and photon energy, which were then used to calculate the corresponding PDDs and dose profiles for various depths and field sizes. Root mean square differences (RMSDs) between the calculated and the measured doses were evaluated for the PDDs and the dose profiles. The RMSDs of PDDs beyond the maximum dose depth were within an accuracy of 0.2-0.6%, being clinically acceptable. The RMSDs of the dose profiles corresponding to the CC13, the CC01, and the edge detector were 2.80%, 1.49%, and 1.46% for a beam energy of 6 MV and 2.34%, 1.15%, and 1.44% for a beam energy of 15 MV, respectively. The calculated results for the CC13 ion chamber showed the most discrepancy compared to the measured data, due to the relatively large sensitive volume of this detector. However, the calculated dose profiles for the detectors were not significantly different from another. The physical algorithm used in the beam-modeling process did not seem to be sensitive to blurred data measured with detectors with large sensitive volumes. Each beam-model was used to clinically evaluate lung and lymphatic node SBRT plans

  16. 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. PMID:26455769

  17. 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.

  18. A Combined Motivation and Parent-Child Interaction Therapy Package Reduces Child Welfare Recidivism in a Randomized Dismantling Field Trial

    ERIC Educational Resources Information Center

    Chaffin, Mark; Funderburk, Beverly; Bard, David; Valle, Linda Anne; Gurwitch, Robin

    2011-01-01

    Objective: A package of parent-child interaction therapy (PCIT) combined with a self-motivational (SM) orientation previously was found in a laboratory trial to reduce child abuse recidivism compared with services as usual (SAU). Objectives of the present study were to test effectiveness in a field agency rather than in a laboratory setting and to…

  19. Capturing Callisto

    NASA Technical Reports Server (NTRS)

    2007-01-01

    The New Horizons Long Range Reconnaissance Imager (LORRI) captured these two images of Jupiter's outermost large moon, Callisto, as the spacecraft flew past Jupiter in late February. New Horizons' closest approach distance to Jupiter was 2.3 million kilometers (1.4 million miles), not far outside Callisto's orbit, which has a radius of 1.9 million kilometers (1.2 million miles). However, Callisto happened to be on the opposite side of Jupiter during the spacecraft's pass through the Jupiter system, so these images, taken from 4.7 million kilometers (3.0 million miles) and 4.2 million kilometers (2.6 million miles) away, are the closest of Callisto that New Horizons obtained.

    Callisto's ancient, crater-scarred surface makes it very different from its three more active sibling satellites, Io, Europa and Ganymede. Callisto, 4,800 kilometers (3000 miles) in diameter, displays no large-scale geological features other than impact craters, and every bright spot in these images is a crater. The largest impact feature on Callisto, the huge basin Valhalla, is visible as a bright patch at the 10 o'clock position. The craters are bright because they have excavated material relatively rich in water ice from beneath the dark, dusty material that coats most of the surface.

    The two images show essentially the same side of Callisto -- the side that faces Jupiter -- under different illumination conditions. The images accompanied scans of Callisto's infrared spectrum with New Horizons' Linear Etalon Imaging Spectral Array (LEISA). The New Horizons science team designed these scans to study how the infrared spectrum of Callisto's water ice changes as lighting and viewing conditions change, and as the ice cools through Callisto's late afternoon. The infrared spectrum of water ice depends slightly on its temperature, and a goal of New Horizons when it reaches the Pluto system (in 2015) is to use the water ice features in the spectrum of Pluto's moon Charon, and

  20. How Well Can the NARCCAP Models Capture the High-Resolution Spatial Patterns of the Precipitation Field in the Western United States

    NASA Astrophysics Data System (ADS)

    Chu, W.; Sellars, S.; Gao, X.; Sorooshian, S.

    2011-12-01

    In the western U.S. where complex terrains present, accurate information on high-resolution spatial distribution of precipitation is critical to many important issues, such as flood/landslide warning, reservoir operation, and water system planning. For instance, due to the highly heterogeneous spatial distribution of precipitation in California, vast manmade infrastructures, such as the Central Valley Project and California Water Project, have been built to resolve the mismatch between where precipitation falls and where water is consumed. In the face of climate variability, prudent planning and proper operation of these water infrastructures are essential to the region's sustainability. The success of planning requires accurate precipitation projection from climate models. In particular, two questions: 1) how well climate models can simulate the precipitation spatial patterns, and 2) how these patterns will change will climate, are of great interest to many researchers and managers in environmental planning and management. Our study are designed to answer these questions based on the dynamical downscaling results from the NARRCAP program and our recent findings on the high-resolution spatial patterns of the daily precipitation field in the western U.S. Using EOF analysis on the U.S. daily precipitation product of Climate Prediction Center (CPC), we revealed that there exists dominant spatial patterns in the precipitation field over the western United States. The spatial patterns are consistent at different spatial resolutions and persistent over decades. Therefore, we intend to evaluate how well climate models can capture these spatial patterns of observed precipitation in this region. EOF analysis is applied to precipitation outputs from NARRCAP, and the derived spatial patterns are compared with those of observation for the same time period. The similarity between model simulations and observation is quantified with mutual information based on Shannon entropy

  1. Dosimetric impact of number of treatment fields in uniform scanning proton therapy planning of lung cancer.

    PubMed

    Rana, Suresh; Simpson, Hilarie; Larson, Gary; Zheng, Yuanshui

    2014-10-01

    The main purpose of this study was to perform a treatment planning study for lung cancer comparing 2-field (2F) versus 3-field (3F) techniques in uniform scanning proton therapy (USPT). Ten clinically approved lung cancer treatment plans delivered using USPT at our proton center were included in this retrospective study. All 10 lung cases included 4D computed tomography (CT) simulation. The delineation of target volumes was done based on the maximum intensity projection (MIP) images. Both the 3F and 2F treatment plans were generated for the total dose of 74 cobalt-gray-equivalent (CGE) with a daily dose of 2 CGE. 3F plan was generated by adding an extra beam in the 2F plan. Various dosimetric parameters between 2F and 3F plans were evaluated. 3F plans produced better target coverage and conformality as well as lower mean dose to the lung, with absolute difference between 3F and 2F plans within 2%. In contrast, the addition of third beam led to increase of low-dose regions (V20 and V5) in the lung in 3F plans compared to the ones in 2F plans with absolute difference within 2%. Maximum dose to the spinal cord was lower in 2F plans. Mean dose to the heart and esophagus were comparable in both 3F and 2F plans. In conclusion, the 3F technique in USPT produced better target coverage and conformality, but increased the low-dose regions in the lung when compared to 2F technique.

  2. Dosimetric impact of number of treatment fields in uniform scanning proton therapy planning of lung cancer

    PubMed Central

    Rana, Suresh; Simpson, Hilarie; Larson, Gary; Zheng, Yuanshui

    2014-01-01

    The main purpose of this study was to perform a treatment planning study for lung cancer comparing 2-field (2F) versus 3-field (3F) techniques in uniform scanning proton therapy (USPT). Ten clinically approved lung cancer treatment plans delivered using USPT at our proton center were included in this retrospective study. All 10 lung cases included 4D computed tomography (CT) simulation. The delineation of target volumes was done based on the maximum intensity projection (MIP) images. Both the 3F and 2F treatment plans were generated for the total dose of 74 cobalt-gray-equivalent (CGE) with a daily dose of 2 CGE. 3F plan was generated by adding an extra beam in the 2F plan. Various dosimetric parameters between 2F and 3F plans were evaluated. 3F plans produced better target coverage and conformality as well as lower mean dose to the lung, with absolute difference between 3F and 2F plans within 2%. In contrast, the addition of third beam led to increase of low-dose regions (V20 and V5) in the lung in 3F plans compared to the ones in 2F plans with absolute difference within 2%. Maximum dose to the spinal cord was lower in 2F plans. Mean dose to the heart and esophagus were comparable in both 3F and 2F plans. In conclusion, the 3F technique in USPT produced better target coverage and conformality, but increased the low-dose regions in the lung when compared to 2F technique. PMID:25525308

  3. Pulsed light imaging for wide-field dosimetry of photodynamic therapy in the skin

    NASA Astrophysics Data System (ADS)

    Davis, Scott C.; Sexton, Kristian; Chapman, Michael Shane; Maytin, Edward; Hasan, Tayyaba; Pogue, Brian W.

    2014-03-01

    Photodynamic therapy using aminoluvelinic acid (ALA) is an FDA-approved treatment for actinic keratoses, pre-cancerous skin lesions which pose a significant risk for immunocompromised individuals, such as organ transplant recipients. While PDT is generally effective, response rates vary, largely due to variations in the accumulation of the photosensitizer protoporphyrin IX (PpIX) after ALA application. The ability to quantify PpIX production before treatment could facilitate the use of additional interventions to improve outcomes. While many groups have demonstrated the ability to image PpIX in the clinic, these systems generally require darkening the room lights during imaging, which is unpopular with clinicians. We have developed a novel wide-field imaging system based on pulsed excitation and gated acquisition to image photosensitizer activity in the skin. The tissue is illuminated using four pulsed LED's to excite PpIX, and the remitted light acquired with a synchronized ICCD. This approach facilitates real-time background subtraction of ambient light, precluding the need to darken the exam room. Delivering light in short bursts also allows the use of elevated excitation intensity while remaining under the maximum permissible exposure limits, making the modality more sensitive to photosensitizer fluorescence than standard approaches. Images of tissue phantoms indicate system sensitivity down to 250nM PpIX and images of animals demonstrate detection of PpIX fluorescence in vivo under normal room light conditions.

  4. 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.

  5. Modern Radiation Therapy for Hodgkin Lymphoma: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group (ILROG)

    SciTech Connect

    Specht, Lena; Yahalom, Joachim; Illidge, Tim; Berthelsen, Anne Kiil; Constine, Louis S.; Eich, Hans Theodor; Girinsky, Theodore; Hoppe, Richard T.; Mauch, Peter; Mikhaeel, N. George; Ng, Andrea

    2014-07-15

    Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solely on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the

  6. A comprehensive spectrometry study of a stray neutron radiation field in scanning proton therapy.

    PubMed

    Mares, Vladimir; Romero-Expósito, Maite; Farah, Jad; Trinkl, Sebastian; Domingo, Carles; Dommert, Martin; Stolarczyk, Liliana; Van Ryckeghem, Laurent; Wielunski, Marek; Olko, Pawel; Harrison, Roger M

    2016-06-01

    The purpose of this study is to characterize the stray neutron radiation field in scanning proton therapy considering a pediatric anthropomorphic phantom and a clinically-relevant beam condition. Using two extended-range Bonner sphere spectrometry systems (ERBSS), Working Group 9 of the European Radiation Dosimetry Group measured neutron spectra at ten different positions around a pediatric anthropomorphic phantom irradiated for a brain tumor with a scanning proton beam. This study compares the different systems and unfolding codes as well as neutron spectra measured in similar conditions around a water tank phantom. The ten spectra measured with two ERBSS systems show a generally similar thermal component regardless of the position around the phantom while high energy neutrons (above 20 MeV) were only registered at positions near the beam axis (at 0°, 329° and 355°). Neutron spectra, fluence and ambient dose equivalent, H (*)(10), values of both systems were in good agreement (<15%) while the unfolding code proved to have a limited effect. The highest H (*)(10) value of 2.7 μSv Gy(-1) was measured at 329° to the beam axis and 1.63 m from the isocenter where high-energy neutrons (E  ⩾  20 MeV) contribute with about 53%. The neutron mapping within the gantry room showed that H (*)(10) values significantly decreased with distance and angular position with respect to the beam axis dropping to 0.52 μSv Gy(-1) at 90° and 3.35 m. Spectra at angles of 45° and 135° with respect to the beam axis measured here with an anthropomorphic phantom showed a similar peak structure at the thermal, fast and high energy range as in the previous water-tank experiments. Meanwhile, at 90°, small differences at the high-energy range were observed. Using ERBSS systems, neutron spectra mapping was performed to characterize the exposure of scanning proton therapy patients. The ten measured spectra provide precise information about the exposure of healthy organs to

  7. A comprehensive spectrometry study of a stray neutron radiation field in scanning proton therapy

    NASA Astrophysics Data System (ADS)

    Mares, Vladimir; Romero-Expósito, Maite; Farah, Jad; Trinkl, Sebastian; Domingo, Carles; Dommert, Martin; Stolarczyk, Liliana; Van Ryckeghem, Laurent; Wielunski, Marek; Olko, Pawel; Harrison, Roger M.

    2016-06-01

    The purpose of this study is to characterize the stray neutron radiation field in scanning proton therapy considering a pediatric anthropomorphic phantom and a clinically-relevant beam condition. Using two extended-range Bonner sphere spectrometry systems (ERBSS), Working Group 9 of the European Radiation Dosimetry Group measured neutron spectra at ten different positions around a pediatric anthropomorphic phantom irradiated for a brain tumor with a scanning proton beam. This study compares the different systems and unfolding codes as well as neutron spectra measured in similar conditions around a water tank phantom. The ten spectra measured with two ERBSS systems show a generally similar thermal component regardless of the position around the phantom while high energy neutrons (above 20 MeV) were only registered at positions near the beam axis (at 0°, 329° and 355°). Neutron spectra, fluence and ambient dose equivalent, H *(10), values of both systems were in good agreement (<15%) while the unfolding code proved to have a limited effect. The highest H *(10) value of 2.7 μSv Gy-1 was measured at 329° to the beam axis and 1.63 m from the isocenter where high-energy neutrons (E  ⩾  20 MeV) contribute with about 53%. The neutron mapping within the gantry room showed that H *(10) values significantly decreased with distance and angular position with respect to the beam axis dropping to 0.52 μSv Gy-1 at 90° and 3.35 m. Spectra at angles of 45° and 135° with respect to the beam axis measured here with an anthropomorphic phantom showed a similar peak structure at the thermal, fast and high energy range as in the previous water-tank experiments. Meanwhile, at 90°, small differences at the high-energy range were observed. Using ERBSS systems, neutron spectra mapping was performed to characterize the exposure of scanning proton therapy patients. The ten measured spectra provide precise information about the exposure of healthy organs to thermal

  8. A comprehensive spectrometry study of a stray neutron radiation field in scanning proton therapy

    NASA Astrophysics Data System (ADS)

    Mares, Vladimir; Romero-Expósito, Maite; Farah, Jad; Trinkl, Sebastian; Domingo, Carles; Dommert, Martin; Stolarczyk, Liliana; Van Ryckeghem, Laurent; Wielunski, Marek; Olko, Pawel; Harrison, Roger M.

    2016-06-01

    The purpose of this study is to characterize the stray neutron radiation field in scanning proton therapy considering a pediatric anthropomorphic phantom and a clinically-relevant beam condition. Using two extended-range Bonner sphere spectrometry systems (ERBSS), Working Group 9 of the European Radiation Dosimetry Group measured neutron spectra at ten different positions around a pediatric anthropomorphic phantom irradiated for a brain tumor with a scanning proton beam. This study compares the different systems and unfolding codes as well as neutron spectra measured in similar conditions around a water tank phantom. The ten spectra measured with two ERBSS systems show a generally similar thermal component regardless of the position around the phantom while high energy neutrons (above 20 MeV) were only registered at positions near the beam axis (at 0°, 329° and 355°). Neutron spectra, fluence and ambient dose equivalent, H *(10), values of both systems were in good agreement (<15%) while the unfolding code proved to have a limited effect. The highest H *(10) value of 2.7 μSv Gy‑1 was measured at 329° to the beam axis and 1.63 m from the isocenter where high-energy neutrons (E  ⩾  20 MeV) contribute with about 53%. The neutron mapping within the gantry room showed that H *(10) values significantly decreased with distance and angular position with respect to the beam axis dropping to 0.52 μSv Gy‑1 at 90° and 3.35 m. Spectra at angles of 45° and 135° with respect to the beam axis measured here with an anthropomorphic phantom showed a similar peak structure at the thermal, fast and high energy range as in the previous water-tank experiments. Meanwhile, at 90°, small differences at the high-energy range were observed. Using ERBSS systems, neutron spectra mapping was performed to characterize the exposure of scanning proton therapy patients. The ten measured spectra provide precise information about the exposure of healthy organs to thermal

  9. Sound Field Amplification: Effects on Managerial Time in Small Group Speech Therapy

    ERIC Educational Resources Information Center

    Meeks, Jeffrey Craig

    2011-01-01

    This study addresses the use of speech amplification devices in speech therapy sessions. The major factor addressed is the impact that speech amplification has upon the managerial time of speech-language pathologists who provide therapy in small group sessions. This study measured the change in the amount of time speech-language pathologists spent…

  10. Enhancing Foster Parent Training with Parent-Child Interaction Therapy: Evidence from a Randomized Field Experiment

    PubMed Central

    Mersky, Joshua P.; Topitzes, James; Janczewski, Colleen E.; McNeil, Cheryl B.

    2015-01-01

    Objective Research indicates that foster parents often do not receive sufficient training and support to help them meet the demands of caring for foster children with emotional and behavioral disturbances. Parent-Child Interaction Therapy (PCIT) is a clinically efficacious intervention for child externalizing problems, and it also has been shown to mitigate parenting stress and enhance parenting attitudes and behaviors. However, PCIT is seldom available to foster families, and it rarely has been tested under intervention conditions that are generalizable to community-based child welfare service contexts. To address this gap, PCIT was adapted and implemented in a field experiment using 2 novel approaches—group-based training and telephone consultation—both of which have the potential to be integrated into usual care. Method This study analyzes 129 foster-parent-child dyads who were randomly assigned to 1 of 3 conditions: (a) waitlist control, (b) brief PCIT, and (c) extended PCIT. Self-report and observational data were gathered at multiple time points up to 14 weeks post baseline. Results Findings from mixed-model, repeated measures analyses indicated that the brief and extended PCIT interventions were associated with a significant decrease in self-reported parenting stress. Results from mixed-effects generalized linear models showed that the interventions also led to significant improvements in observed indicators of positive and negative parenting. The brief course of PCIT was as efficacious as the extended PCIT intervention. Conclusions The findings suggest that usual training and support services can be improved upon by introducing foster parents to experiential, interactive PCIT training. PMID:26977251

  11. Towards the optimisation of acoustic fields for ablative therapies of tumours in the upper abdomen

    NASA Astrophysics Data System (ADS)

    Gélat, P.; ter Haar, G.; Saffari, N.

    2013-08-01

    The efficacy of high intensity focused ultrasound (HIFU) for the non-invasive treatment of cancer has been demonstrated for a range of different cancers including those of the liver, kidney, prostate and breast. As a non-invasive focused therapy, HIFU offers considerable advantages over other techniques such as chemotherapy and surgical resection, in terms of its non-invasiveness and low risk of harmful side effects. There is, however, a number of significant challenges which currently hinder its widespread clinical application. One of these challenges is the need to transmit sufficient energy through the ribcage to induce tissue necrosis at the required foci whilst minimising the formation of side lobes and sparing healthy tissue. Ribs both absorb and reflect ultrasound strongly. As such, a common side effect of focusing ultrasound in regions located behind the rib cage is the overheating of bone and surrounding tissue, which can lead to skin burns. Successful treatment of a patient with tumours in the upper abdomen therefore requires a thorough understanding of the way acoustic and thermal energy are deposited. This is likely to rely on a treatment planning procedure in which optimal source velocity distributions are obtained so as to maximise a dose quantity at the treatment sites, whilst ensuring that this quantity does not exceed a specified threshold at other field locations, particularly on the surface of the ribs. Previously, a boundary element approach based on a Generalised Minimal Residual (GMRES) implementation of the Burton-Miller formulation was developed to predict the field of a multi-element HIFU array scattered by human ribs, the topology of which was obtained from CT scan data [1]. This work describes the reformulation of the boundary element equations as a least-squares minimisation problem with non-linear constraints. The methodology was subsequently tested at an excitation frequency of 100 kHz on a spherical multi-element array in the presence

  12. Enhancing Predicted Efficacy of Tumor Treating Fields Therapy of Glioblastoma Using Targeted Surgical Craniectomy: A Computer Modeling Study

    PubMed Central

    Korshoej, Anders Rosendal; Saturnino, Guilherme Bicalho; Rasmussen, Line Kirkegaard; von Oettingen, Gorm; Sørensen, Jens Christian Hedemann; Thielscher, Axel

    2016-01-01

    Objective The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. Methods We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic clinical scenarios. Results For the superficial tumor, removal of a standard craniotomy bone flap increased the electrical field strength by 60–70% in the tumor. The percentage of tissue in expected growth arrest or regression was increased from negligible values to 30–50%. The observed effects were highly focal and targeted at the regions of pathology underlying the craniectomy. No significant changes were observed in surrounding healthy tissues. Median field strengths in tumor tissue increased with increasing craniectomy diameter up to 50–70 mm. Multiple smaller burr holes were more efficient than single craniectomies of equivalent area. Craniectomy caused no significant field enhancement in the deeply seated tumor, but rather a focal enhancement in the brain tissue underlying the skull defect. Conclusions Our results provide theoretical evidence that small and clinically feasible craniectomies may provide significant enhancement of TTFields intensity in cerebral hemispheric tumors without severely compromising brain protection or causing unacceptable heating in

  13. SU-E-T-296: Single Field Per Day Vs. Multiple Fields Per Day and the Impact On BED in Proton Therapy Treatment

    SciTech Connect

    Grantham, K; Wooten, H; Zhao, T; Klein, E

    2014-06-01

    Purpose: A common practice, in proton therapy, is to deliver a rotating subset of fields from the treatment plan for the daily fractions. This study compares the impact this practice has on the biological effective dose (BED) versus delivering all planned fields daily. Methods: For two scenarios (a phantom with a geometry approximating the anatomy of a prostate treatment with opposing lateral beams, and a clinical 3-field brain treatment), treatment plans were produced in Eclipse (Varian) to simulate delivery of one, two, and three fields per fraction. The RT-Dose file, structure set, and α/β ratios were processed using in-house MATLAB code to return a new RT-Dose file containing the BED (including a proton RBE of 1.1) which was imported back into Eclipse for analysis. Results: For targets and regions of field overlap in the treatment plan, BED is not affected by delivery regimen. In the phantom, BED in the femoral heads showed increased by 20% when a single field was used rather than two fields. In the brain treatment, the minimum BED to the left optic nerve and the pituitary gland increased by 13% and 10% respectively, for a one-field regime compared to three-fields per fraction. Comparing the two-field and threefield regimes, the optic nerve BED was not significantly affected and the minimum pituitary BED was 4% higher for two fields per day. Conclusion: Hypo-fractionation effects, in regions of non-overlap of fields, significantly increase the BED to the involved tissues by as much as 20%. Care should be taken to avoid inadvertently sacrificing plan effectiveness in the interest of reduced treatment time.

  14. 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.

  15. Split-field vs extended-field intensity-modulated radiation therapy plans for oropharyngeal cancer: Which spares the larynx? Which spares the thyroid?

    PubMed

    Yu, Yao; Chen, Josephine; Leary, Celeste I; Shugard, Erin; Yom, Sue S

    2016-01-01

    Radiation of the low neck can be accomplished using split-field intensity-modulated radiation therapy (sf-IMRT) or extended-field intensity-modulated radiation therapy (ef-IMRT). We evaluated the effect of these treatment choices on target coverage and thyroid and larynx doses. Using data from 14 patients with cancers of the oropharynx, we compared the following 3 strategies for radiating the low neck: (1) extended-field IMRT, (2) traditional split-field IMRT with an initial cord-junction block to 40Gy, followed by a full-cord block to 50Gy, and (3) split-field IMRT with a full-cord block to 50Gy. Patients were planned using each of these 3 techniques. To facilitate comparison, extended-field plans were normalized to deliver 50Gy to 95% of the neck volume. Target coverage was assessed using the dose to 95% of the neck volume (D95). Mean thyroid and larynx doses were computed. Extended-field IMRT was used as the reference arm; the mean larynx dose was 25.7 ± 7.4Gy, and the mean thyroid dose was 28.6 ± 2.4Gy. Split-field IMRT with 2-step blocking reduced laryngeal dose (mean larynx dose 15.2 ± 5.1Gy) at the cost of a moderate reduction in target coverage (D95 41.4 ± 14Gy) and much higher thyroid dose (mean thyroid dose 44.7 ± 3.7Gy). Split-field IMRT with initial full-cord block resulted in greater laryngeal sparing (mean larynx dose 14.2 ± 5.1Gy) and only a moderately higher thyroid dose (mean thyroid dose 31 ± 8Gy) but resulted in a significant reduction in target coverage (D95 34.4 ± 15Gy). Extended-field IMRT comprehensively covers the low neck and achieves acceptable thyroid and laryngeal sparing. Split-field IMRT with a full-cord block reduces laryngeal doses to less than 20Gy and spares the thyroid, at the cost of substantially reduced coverage of the low neck. Traditional 2-step split-field IMRT similarly reduces the laryngeal dose but also reduces low-neck coverage and delivers very high doses to the thyroid.

  16. Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies

    SciTech Connect

    Salama, Joseph K. . E-mail: jsalama@radonc.uchicago.edu; Mundt, Arno J.; Roeske, John; Mehta, Neil

    2006-07-15

    Purpose: The aim of this article is to report a preliminary analysis of our initial clinical experience with extended-field intensity-modulated radiotherapy for gynecologic malignancies. Methods and Materials: Between November 2002 and May 2005, 13 women with gynecologic malignancies were treated with extended-field radiation therapy. Of the women, 7 had endometrial cancer, 4 cervical cancer, 1 recurrent endometrial cancer, and 1 suspected cervical cancer. All women underwent computed tomography planning, with the upper vagina, parametria, and uterus (if present) contoured within the CTV. In addition, the clinical target volume contained the pelvic and presacral lymph nodes as well as the para-aortic lymph nodes. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE v 3.0). All late toxicity was scored using the Radiation Therapy Oncology Group late toxicity score. Results: The median follow-up was 11 months. Extended-field intensity-modulated radiation therapy (IMRT) for gynecologic malignancies was well tolerated. Two patients experienced Grade 3 or higher toxicity. Both patients were treated with concurrent cisplatin based chemotherapy. Neither patient was planned with bone marrow sparing. Eleven patients had no evidence of late toxicity. One patient with multiple previous surgeries experienced a bowel obstruction. One patient with bilateral grossly involved and unresectable common iliac nodes experienced bilateral lymphedema. Extended-field-IMRT achieved good local control with only 1 patient, who was metastatic at presentation, and 1 patient not able to complete treatment, experiencing in-field failure. Conclusions: Extended-field IMRT is safe and effective with a low incidence of acute toxicity. Longer follow-up is needed to assess chronic toxicity, although early results are promising.

  17. Exploring the influence of gestalt therapy training on psychiatric nursing practice: stories from the field.

    PubMed

    Kelly, Teresa; Howie, Linsey

    2011-08-01

    Psychiatric nurses interested in extending their interpersonal and psychotherapeutic skills sometimes undertake postgraduate training in gestalt therapy. Little is known about how this new knowledge and psychotherapeutic skill base informs their practice. This paper presents the findings of a qualitative study that aimed to explore the influence of gestalt therapy training on psychiatric nursing practice. Within a framework of narrative inquiry, four psychiatric nurses trained in gestalt therapy were invited to tell their stories of training in a gestalt approach to therapy, and recount their experiences of how it influenced their practice. In keeping with narrative analysis methods, the research findings were presented as a collection of four stories. Eight themes were derived from a thematic analysis conducted within and across the four stories. The discussion of the themes encapsulates the similarities and differences across the storied collection, providing a community and cultural context for understanding the individual stories. PMID:21429062

  18. Exploring the influence of gestalt therapy training on psychiatric nursing practice: stories from the field.

    PubMed

    Kelly, Teresa; Howie, Linsey

    2011-08-01

    Psychiatric nurses interested in extending their interpersonal and psychotherapeutic skills sometimes undertake postgraduate training in gestalt therapy. Little is known about how this new knowledge and psychotherapeutic skill base informs their practice. This paper presents the findings of a qualitative study that aimed to explore the influence of gestalt therapy training on psychiatric nursing practice. Within a framework of narrative inquiry, four psychiatric nurses trained in gestalt therapy were invited to tell their stories of training in a gestalt approach to therapy, and recount their experiences of how it influenced their practice. In keeping with narrative analysis methods, the research findings were presented as a collection of four stories. Eight themes were derived from a thematic analysis conducted within and across the four stories. The discussion of the themes encapsulates the similarities and differences across the storied collection, providing a community and cultural context for understanding the individual stories.

  19. Assessment of radiation-induced second cancer risks in proton therapy and IMRT for organs inside the primary radiation field

    NASA Astrophysics Data System (ADS)

    Paganetti, Harald; Athar, Basit S.; Moteabbed, Maryam; Adams, Judith A.; Schneider, Uwe; Yock, Torunn I.

    2012-10-01

    There is clinical evidence that second malignancies in radiation therapy occur mainly within the beam path, i.e. in the medium or high-dose region. The purpose of this study was to assess the risk for developing a radiation-induced tumor within the treated volume and to compare this risk for proton therapy and intensity-modulated photon therapy (IMRT). Instead of using data for specific patients we have created a representative scenario. Fully contoured age- and gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a treatment planning system and tumor volumes were contoured based on patients treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for IMRT and proton therapy treatments were generated. Lifetime attributable risks (LARs) for developing a second malignancy were calculated using a risk model considering cell kill, mutation, repopulation, as well as inhomogeneous organ doses. For standard fractionation schemes, the LAR for developing a second malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year old optic glioma patient treated with IMRT considering a soft-tissue carcinoma risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14 year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma cases the risks based on a sarcoma model were typically higher than the carcinoma risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from proton therapy turned out to be lower by at least a factor of 2 and up to a factor of 10. This is mainly due to lower total energy deposited in the patient when using proton beams. However, the comparison of a three-field and four-field proton plan also shows that the distribution of the dose, i.e. the particular treatment plan, plays a role. When using different fractionation schemes, the estimated risks roughly scale with the total dose difference in%. In conclusion, proton therapy can

  20. Ultrasound generation and high-frequency motion of magnetic nanoparticles in an alternating magnetic field: Toward intracellular ultrasound therapy?

    NASA Astrophysics Data System (ADS)

    Carrey, J.; Connord, V.; Respaud, M.

    2013-06-01

    We show theoretically that, in an inhomogeneous alternating magnetic field of frequency f, due to the alternating gradient, magnetic nanoparticles oscillate mechanically and generate ultrasound waves. This effect is maximized and better controlled if a static magnetic field is superimposed to an alternating gradient. It makes possible the generation of ultrasounds intracellularly and might also explain recent experiments in magnetic hyperthermia in which cells have been killed without any global temperature increase. Combined to an efficient targeting, it could permit ultrasound therapy with an unprecedented spatial resolution.

  1. Analysis of 18F-fluorodeoxy-glucose PET imaging data captured before and after Pc 4-mediated photodynamic therapy of U87 tumors in the athymic nude rat

    NASA Astrophysics Data System (ADS)

    Cross, Nathan; Varghai, Davood; Spring-Robinson, Chandra; Sharma, Rahul; Muzic, Raymond F., Jr.; Oleinick, Nancy L.; Dean, D.

    2007-02-01

    Introduction: Several workers have proposed the use of PET (Positron Emission Tomography) imaging for the outcome assessment of photodynamic therapy (PDT), especially for deep-seated tumors. We report on our study of 18Ffluorodeoxy- glucose (18F-FDG) PET imaging following brain tumor Pc4-PDT. Our working hypothesis was that the tumor's metabolic activity would decline dramatically following Pc 4-PDT owing to tumor necrosis. Methods: Seven days after intraparenchymal implantation of U87 cells, the brains of 12 athymic nude rats were imaged by micro-CT and/or micro-MR. These animals were also 18F-FDG micro-PET (μPET) scanned before and after Pc 4-PDT. 18F-FDG was used to trace metabolic activity that was monitored via μPET. Occurrence of PDT was confirmed on histology. The analysis of 18F-FDG dose and animal weight normalized μPET activity was studied over the 90 minute µPET scan. Results: Currently, μPET data have been studied for: (1) three of the animals that did not indicate tumor necrosis on histology and were assigned to a "Non-PDT" group, and (2) six animals that exhibited tumor necrosis on histology and were assigned to a "PDT" group. The μPET-detected 18F-FDG uptake activity in the tumor region before and after photoirradiation increased in the Non-PDT group an average of 2.28 times, and in the PDT group it increased an average of 1.15 times. Discussion: We are investigating the cause of the increase in 18F-FDG μPET activity that we observed in the PDT group. The methodology used in this study should be useful in determining whether this or other PET, SPECT, or MR functional imaging protocols will detect both the specificity and sensitivity of brain tumor necrosis following Pc 4-PDT.

  2. Regional electric field induced by electroconvulsive therapy in a realistic finite element head model: influence of white matter anisotropic conductivity.

    PubMed

    Lee, Won Hee; Deng, Zhi-De; Kim, Tae-Seong; Laine, Andrew F; Lisanby, Sarah H; Peterchev, Angel V

    2012-02-01

    We present the first computational study investigating the electric field (E-field) strength generated by various electroconvulsive therapy (ECT) electrode configurations in specific brain regions of interest (ROIs) that have putative roles in the therapeutic action and/or adverse side effects of ECT. This study also characterizes the impact of the white matter (WM) conductivity anisotropy on the E-field distribution. A finite element head model incorporating tissue heterogeneity and WM anisotropic conductivity was constructed based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. We computed the spatial E-field distributions generated by three standard ECT electrode placements including bilateral (BL), bifrontal (BF), and right unilateral (RUL) and an investigational electrode configuration for focal electrically administered seizure therapy (FEAST). The key results are that (1) the median E-field strength over the whole brain is 3.9, 1.5, 2.3, and 2.6 V/cm for the BL, BF, RUL, and FEAST electrode configurations, respectively, which coupled with the broad spread of the BL E-field suggests a biophysical basis for observations of superior efficacy of BL ECT compared to BF and RUL ECT; (2) in the hippocampi, BL ECT produces a median E-field of 4.8 V/cm that is 1.5-2.8 times stronger than that for the other electrode configurations, consistent with the more pronounced amnestic effects of BL ECT; and (3) neglecting the WM conductivity anisotropy results in E-field strength error up to 18% overall and up to 39% in specific ROIs, motivating the inclusion of the WM conductivity anisotropy in accurate head models. This computational study demonstrates how the realistic finite element head model incorporating tissue conductivity anisotropy provides quantitative insight into the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation paradigms

  3. Clinical phase-I study of Na[sub 2]B[sub 12]H[sub 11]SH (BSH) in patients with malignant glioma as precondition for boron neutron capture therapy (BNCT)

    SciTech Connect

    Haritz, D. ); Gabel, D. ); Huiskamp, R. )

    1994-03-30

    Within the European collaboration on boron neutron capture therapy (BNCT), a clinical Phase I study is being carried out to establish BNCT as an alternative treatment modality for malignant glioma (WHO III/IV). Data about the pharmacokinetics, biodistribution and toxicity of the boron compound Na[sub 2]B[sub 12]H[sub 11]SH (BSH) are of great importance to avoid radiation damage of healthy tissue and to deliver a sufficient radiation dose. Twenty four patients suffering from a glioblastoma multiforme entered the study to date, infused with a maximum concentration of up to 50 mg BSH/kg. Boron concentration measurements in tissues, urine, and blood were carried out, using inductively coupled plasma-atomic spectroscopy (ICP-AES) and quantitative neutron capture radiography (QNCR). A cross-calibration of these determination techniques was carried out. In tumor tissue, confirmed by histopathology of small biopsies, they found a consistently high but heterogeneous boron uptake. Necrotic parts contain much lower amounts of boron; normal brain tissue has shown no significant uptake. In skin, bone, muscle, and dura mater only small amounts of boron were found. In blood samples, they found biphasic kinetics, but with variations of the half-lives from patient to patient. The compound is mainly excreted through the urine, but an additional entero-hapatic pathway can be demonstrated. Systematic investigations revealed no toxic side effect of the intravenously administered BSH. Comparable data were obtained by using ICP-AES and QNCR for boron concentration measurements. Taking into account the radiobiological considerations of the neutron beam source, they found promising facts that BNCT could be a useful irradiation method for highly malignant brain tumors. Favorable amounts of the boron compound BSH were found in tumor tissue, whereas healthy brain tissue has shown no significant uptake. 16 refs., 8 figs., 2 tabs.

  4. Biodistribution and subcellular localization of an unnatural boron-containing amino acid (cis-ABCPC) by imaging secondary ion mass spectrometry for neutron capture therapy of melanomas and gliomas.

    PubMed

    Chandra, Subhash; Barth, Rolf F; Haider, Syed A; Yang, Weilian; Huo, Tianyao; Shaikh, Aarif L; Kabalka, George W

    2013-01-01

    The development of new boron-delivery agents is a high priority for improving the effectiveness of boron neutron capture therapy. In the present study, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC) as a mixture of its L- and D-enantiomers was evaluated in vivo using the B16 melanoma model for the human tumor and the F98 rat glioma as a model for human gliomas. A secondary ion mass spectrometry (SIMS) based imaging instrument, CAMECA IMS 3F SIMS Ion Microscope, was used for quantitative imaging of boron at 500 nm spatial resolution. Both in vivo and in vitro studies in melanoma models demonstrated that boron was localized in the cytoplasm and nuclei with some cell-to-cell variability. Uptake of cis-ABCPC in B16 cells was time dependent with a 7.5:1 partitioning ratio of boron between cell nuclei and the nutrient medium after 4 hrs. incubation. Furthermore, cis-ABCPC delivered boron to cells in all phases of the cell cycle, including S-phase. In vivo SIMS studies using the F98 rat glioma model revealed an 8:1 boron partitioning ratio between the main tumor mass and normal brain tissue with a 5:1 ratio between infiltrating tumor cells and contiguous normal brain. Since cis-ABCPC is water soluble and can cross the blood-brain-barrier via the L-type amino acid transporters (LAT), it may accumulate preferentially in infiltrating tumor cells in normal brain due to up-regulation of LAT in high grade gliomas. Once trapped inside the tumor cell, cis-ABCPC cannot be metabolized and remains either in a free pool or bound to cell matrix components. The significant improvement in boron uptake by both the main tumor mass and infiltrating tumor cells compared to those reported in animal and clinical studies of p-boronophenylalanine strongly suggest that cis-ABCPC has the potential to become a novel new boron delivery agent for neutron capture therapy of gliomas and melanomas.

  5. Biodistribution and Subcellular Localization of an Unnatural Boron-Containing Amino Acid (Cis-ABCPC) by Imaging Secondary Ion Mass Spectrometry for Neutron Capture Therapy of Melanomas and Gliomas

    PubMed Central

    Chandra, Subhash; Barth, Rolf F.; Haider, Syed A.; Yang, Weilian; Huo, Tianyao; Shaikh, Aarif L.; Kabalka, George W.

    2013-01-01

    The development of new boron-delivery agents is a high priority for improving the effectiveness of boron neutron capture therapy. In the present study, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC) as a mixture of its L- and D- enantiomers was evaluated in vivo using the B16 melanoma model for the human tumor and the F98 rat glioma as a model for human gliomas. A secondary ion mass spectrometry (SIMS) based imaging instrument, CAMECA IMS 3F SIMS Ion Microscope, was used for quantitative imaging of boron at 500 nm spatial resolution. Both in vivo and in vitro studies in melanoma models demonstrated that boron was localized in the cytoplasm and nuclei with some cell-to-cell variability. Uptake of cis-ABCPC in B16 cells was time dependent with a 7.5:1 partitioning ratio of boron between cell nuclei and the nutrient medium after 4 hrs. incubation. Furthermore, cis-ABCPC delivered boron to cells in all phases of the cell cycle, including S-phase. In vivo SIMS studies using the F98 rat glioma model revealed an 8:1 boron partitioning ratio between the main tumor mass and normal brain tissue with a 5:1 ratio between infiltrating tumor cells and contiguous normal brain. Since cis-ABCPC is water soluble and can cross the blood-brain-barrier via the L-type amino acid transporters (LAT), it may accumulate preferentially in infiltrating tumor cells in normal brain due to up-regulation of LAT in high grade gliomas. Once trapped inside the tumor cell, cis-ABCPC cannot be metabolized and remains either in a free pool or bound to cell matrix components. The significant improvement in boron uptake by both the main tumor mass and infiltrating tumor cells compared to those reported in animal and clinical studies of p-boronophenylalanine strongly suggest that cis-ABCPC has the potential to become a novel new boron delivery agent for neutron capture therapy of gliomas and melanomas. PMID:24058680

  6. Modern Radiation Therapy for Extranodal Lymphomas: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group

    SciTech Connect

    Yahalom, Joachim; Illidge, Tim; Specht, Lena; Hoppe, Richard T.; Li, Ye-Xiong; Tsang, Richard; Wirth, Andrew

    2015-05-01

    Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL, involving any organ in the body and the spectrum of histological sub-types, poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU), as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype, anatomy, the treatment intent, and other treatment modalities that may be have been used before RT.

  7. Comparison of out-of-field photon doses in 6 MV IMRT and neutron doses in proton therapy for adult and pediatric patients

    NASA Astrophysics Data System (ADS)

    Athar, Basit S.; Bednarz, Bryan; Seco, Joao; Hancox, Cindy; Paganetti, Harald

    2010-05-01

    The purpose of this study was to assess lateral out-of-field doses in 6 MV IMRT (intensity modulated radiation therapy) and compare them with secondary neutron equivalent dose contributions in proton therapy. We simulated out-of-field photon doses to various organs as a function of distance, patient's age, gender and treatment volumes based on 3, 6, 9 cm field diameters in the head and neck and spine region. The out-of-field photon doses to organs near the field edge were found to be in the range of 2, 5 and 10 mSv Gy-1 for 3 cm, 6 cm and 9 cm diameter IMRT fields, respectively, within 5 cm of the field edge. Statistical uncertainties calculated in organ doses vary from 0.2% to 40% depending on the organ location and the organ volume. Next, a comparison was made with previously calculated neutron equivalent doses from proton therapy using identical field arrangements. For example, out-of-field doses for IMRT to lung and uterus (organs close to the 3 cm diameter spinal field) were computed to be 0.63 and 0.62 mSv Gy-1, respectively. These numbers are found to be a factor of 2 smaller than the corresponding out-of-field doses for proton therapy, which were estimated to be 1.6 and 1.7 mSv Gy-1 (RBE), respectively. However, as the distance to the field edge increases beyond approximately 25 cm the neutron equivalent dose from proton therapy was found to be a factor of 2-3 smaller than the out-of-field photon dose from IMRT. We have also analyzed the neutron equivalent doses from an ideal scanned proton therapy (assuming not significant amount of absorbers in the treatment head). Out-of-field doses were found to be an order of magnitude smaller compared to out-of-field doses in IMRT or passive scattered proton therapy. In conclusion, there seem to be three geometrical areas when comparing the out-of-target dose from IMRT and (passive scattered) proton treatments. Close to the target (in-field, not analyzed here) protons offer a distinct advantage due to the lower

  8. Comparison of out-of-field photon doses in 6 MV IMRT and neutron doses in proton therapy for adult and pediatric patients

    PubMed Central

    Athar, Basit S; Bednarz, Bryan; Seco, Joao; Hancox, Cindy; Paganetti, Harald

    2012-01-01

    The purpose of this study was to assess lateral out-of-field doses in 6 MV IMRT (intensity modulated radiation therapy) and compare them with secondary neutron equivalent dose contributions in proton therapy. We simulated outof-field photon doses to various organs as a function of distance, patient's age, gender and treatment volumes based on 3, 6, 9 cm field diameters in the head and neck and spine region. The out-of-field photon doses to organs near the field edge were found to be in the range of 2, 5 and 10 mSv Gy−1 for 3 cm, 6 cm and 9 cm diameter IMRT fields, respectively, within 5 cm of the field edge. Statistical uncertainties calculated in organ doses vary from 0.2% to 40% depending on the organ location and the organ volume. Next, a comparison was made with previously calculated neutron equivalent doses from proton therapy using identical field arrangements. For example, out-of-field doses for IMRT to lung and uterus (organs close to the 3 cm diameter spinal field) were computed to be 0.63 and 0.62 mSv Gy−1, respectively. These numbers are found to be a factor of 2 smaller than the corresponding out-of-field doses for proton therapy, which were estimated to be 1.6 and 1.7 mSv Gy−1 (RBE), respectively. However, as the distance to the field edge increases beyond approximately 25 cm the neutron equivalent dose from proton therapy was found to be a factor of 2–3 smaller than the out-of-field photon dose from IMRT. We have also analyzed the neutron equivalent doses from an ideal scanned proton therapy (assuming not significant amount of absorbers in the treatment head). Outof-field doses were found to be an order of magnitude smaller compared to out-of-field doses in IMRT or passive scattered proton therapy. In conclusion, there seem to be three geometrical areas when comparing the out-of-target dose from IMRT and (passive scattered) proton treatments. Close to the target (in-field, not analyzed here) protons offer a distinct advantage due to the lower

  9. Estimation of capture zones and drawdown at the Northwest and West Well Fields, Miami-Dade County, Florida, using an unconstrained Monte Carlo analysis: recent (2004) and proposed conditions

    USGS Publications Warehouse

    Brakefield, Linzy K.; Hughes, Joseph D.; Langevin, Christian D.; Chartier, Kevin

    2013-01-01

    Travel-time capture zones and drawdown for two production well fields, used for drinking-water supply in Miami-Dade County, southeastern Florida, were delineated by the U.S Geological Survey using an unconstrained Monte Carlo analysis. The well fields, designed to supply a combined total of approximately 250 million gallons of water per day, pump from the highly transmissive Biscayne aquifer in the urban corridor between the Everglades and Biscayne Bay. A transient groundwater flow model was developed and calibrated to field data to ensure an acceptable match between simulated and observed values for aquifer heads and net exchange of water between the aquifer and canals. Steady-state conditions were imposed on the transient model and a post-processing backward particle-tracking approach was implemented. Multiple stochastic realizations of horizontal hydraulic conductivity, conductance of canals, and effective porosity were simulated for steady-state conditions representative of dry, average and wet hydrologic conditions to calculate travel-time capture zones of potential source areas of the well fields. Quarry lakes, formed as a product of rock-mining activities, whose effects have previously not been considered in estimation of capture zones, were represented using high hydraulic-conductivity, high-porosity cells, with the bulk hydraulic conductivity of each cell calculated based on estimates of aquifer hydraulic conductivity, lake depths and aquifer thicknesses. A post-processing adjustment, based on calculated residence times using lake outflows and known lake volumes, was utilized to adjust particle endpoints to account for an estimate of residence-time-based mixing of lakes. Drawdown contours of 0.1 and 0.25 foot were delineated for the dry, average, and wet hydrologic conditions as well. In addition, 95-percent confidence intervals (CIs) were calculated for the capture zones and drawdown contours to delineate a zone of uncertainty about the median estimates

  10. Estimation of capture zones and drawdown at the Northwest and West Well Fields, Miami-Dade County, Florida, using an unconstrained Monte Carlo analysis: recent (2004) and proposed conditions

    USGS Publications Warehouse

    Brakefield, Linzy K.; Hughes, Joseph D.; Langevin, Christian D.; Chartier, Kevin

    2013-01-01

    Travel-time capture zones and drawdown for two production well fields, used for drinking-water supply in Miami-Dade County, southeastern Florida, were delineated by the U.S Geological Survey using an unconstrained Monte Carlo analysis. The well fields, designed to supply a combined total of approximately 250 million gallons of water per day, pump from the highly transmissive Biscayne aquifer in the urban corridor between the Everglades and Biscayne Bay. A transient groundwater flow model was developed and calibrated to field data to ensure an acceptable match between simulated and observed values for aquifer heads and net exchange of water between the aquifer and canals. Steady-state conditions were imposed on the transient model and a post-processing backward particle-tracking approach was implemented. Multiple stochastic realizations of horizontal hydraulic conductivity, conductance of canals, and effective porosity were simulated for steady-state conditions representative of dry, average and wet hydrologic conditions to calculate travel-time capture zones of potential source areas of the well fields. Quarry lakes, formed as a product of rock-mining activities, whose effects have previously not been considered in estimation of capture zones, were represented using high hydraulic-conductivity, high-porosity cells, with the bulk hydraulic conductivity of each cell calculated based on estimates of aquifer hydraulic conductivity, lake depths and aquifer thicknesses. A post-processing adjustment, based on calculated residence times using lake outflows and known lake volumes, was utilized to adjust particle endpoints to account for an estimate of residence-time-based mixing of lakes. Drawdown contours of 0.1 and 0.25 foot were delineated for the dry, average, and wet hydrologic conditions as well. In addition, 95-percent confidence intervals (CIs) were calculated for the capture zones and drawdown contours to delineate a zone of uncertainty about the median estimates

  11. Verification of light & radiation field coincidence quality assurance for radiation therapy by using a-Se based DR system

    NASA Astrophysics Data System (ADS)

    Kim, Jin-Young; Park, Eun-Tae; Choi, Yun-Seon; Cho, Heung-Lae; Ahn, Ki-Jung; Park, Sung-Kwang; Kim, Ji-Na; Suh, Tae-Suk; Kim, Jin-Seon; Hong, Ju-Yeon; Park, Jeong-Eun; Kim, Kyo-Tae; Oh, Kyung-Min; Kim, Hyunjung; Jo, Sun-Mi; Oh, Won-Yong; Jin, Seong-Jin; Cho, Woong

    2015-04-01

    Currently, the American Association of Physicists in Medicine (AAPM) recommends measuring the surface field size once a week by using an analog film in order to verify light and radiation field coincidence in the Quality Assurance (QA) of radiotherapy. However, the use of the film does not allow for a quantitative method of evaluation, and measuring the light field with radiation field detectors in a 2D array is difficult. Therefore, we used an amorphous-Se (a-Se) digital radiation detection system to measure the light and radiation fields simultaneously for a quantitative QA system, and the feasibility of using such a system was confirmed by ensuring the coincidence of the light and the radiation field measurements. The characteristics of the analog film and the a-Se digital radiation detection system were compared by delivering to each doses of 100, 10 monitor units(MU) of radiation at a rate of 400 MU/min to a radiation field 100 × 100 mm2 in size from a 100 cm source-surface distance (SSD). A 0.5 mm to 0.6 mm difference was measured in the X-axis, and a 0.3 mm difference was measured in the Y-axis. The difference in the measurements of the coincidence of light and the radiation field was less than 0.3 mm, which is relatively insignificant. These results indicate that the use of an a-Se digital radiation detection system is adequate for quality assurance of radiotherapy using light and radiation field coincidence. In addition, the experiment is considered to have provided valuable results in that the a-Se based digital radiation detection system enables simple and accurate QA for clinical radiation therapy by assessing the coincidence in the alignment of the light and the radiation fields.

  12. The GEANT4 toolkit capability in the hadron therapy field: simulation of a transport beam line

    NASA Astrophysics Data System (ADS)

    Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.; Raffaele, L.; Russo, G.; Guatelli, S.; Pia, M. G.

    2006-01-01

    At Laboratori Nazionali del Sud of the Instituto Nazionale di Fisica Nucleare of Catania (Sicily, Italy), the first Italian hadron therapy facility named CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) has been realized. Inside CATANA 62 MeV proton beams, accelerated by a superconducting cyclotron, are used for the radiotherapeutic treatments of some types of ocular tumours. Therapy with hadron beams still represents a pioneer technique, and only a few centers worldwide can provide this advanced specialized cancer treatment. On the basis of the experience so far gained, and considering the future hadron-therapy facilities to be developed (Rinecker, Munich Germany, Heidelberg/GSI, Darmstadt, Germany, PSI Villigen, Switzerland, CNAO, Pavia, Italy, Centro di Adroterapia, Catania, Italy) we decided to develop a Monte Carlo application based on the GEANT4 toolkit, for the design, the realization and the optimization of a proton-therapy beam line. Another feature of our project is to provide a general tool able to study the interactions of hadrons with the human tissue and to test the analytical-based treatment planning systems actually used in the routine practice. All the typical elements of a hadron-therapy line, such as diffusers, range shifters, collimators and detectors were modelled. In particular, we simulated the Markus type ionization chamber and a Gaf Chromic film as dosimeters to reconstruct the depth (Bragg peak and Spread Out Bragg Peak) and lateral dose distributions, respectively. We validated our simulated detectors comparing the results with the experimental data available in our facility.

  13. A unique in vivo assessment of 4-[10B]borono-L-phenylalanine in tumour tissues for boron neutron capture therapy of malignant melanomas using positron emission tomography and 4-borono-2-[18F]fluoro-L-phenylalanine.

    PubMed

    Ishiwata, K; Shiono, M; Kubota, K; Yoshino, K; Hatazawa, J; Ido, T; Honda, C; Ichihashi, M; Mishima, Y

    1992-09-01

    A unique in vivo approach to assessing the concentrations of 4-[10B]borono-L-phenylalanine (L-BPA), a melanoma targeting compound for boron neutron capture therapy (BNCT), was investigated using L-BPA labelled with positron-emitting 18F (half-life = 110 min), i.e., 4-[10B]borono-2-[18F]fluoro-L-phenylalanine (L-[18F]FBPA). High melanoma uptake of L-[18F]FBPA was reduced slightly by competition with L-BPA in the two animal models of the murine B16 melanoma and the melanotic Greene's melanoma No. 179 in hamsters. In mice given L-[18F]FBPA and L-BPA, the concentrations of 10B in B16 estimated from 18F radioactivity were lower than those measured by inductively coupled plasma-atomic emission spectroscopy. Lower estimated values were dependent on the time after injection and on the loading dose of L-BPA. The estimated 10B concentrations for Green's melanomas were comparable to the measured values. Positron emission tomography (PET) using L-[18F]FBPA allowed Greene's melanomas to be clearly visualized. In conclusion, when L-[18F]FBPA is used as a probe for L-BPA in BNCT of malignant melanomas, the melanoma can be localized and the 10B concentrations in tissues can be assessed in vivo using 18F radioactivity by PET.

  14. In vivo (19)F MRI and (19)F MRS of (19)F-labelled boronophenylalanine-fructose complex on a C6 rat glioma model to optimize boron neutron capture therapy (BNCT).

    PubMed

    Porcari, Paola; Capuani, Silvia; D'Amore, Emanuela; Lecce, Mario; La Bella, Angela; Fasano, Fabrizio; Campanella, Renzo; Migneco, Luisa Maria; Pastore, Francesco Saverio; Maraviglia, Bruno

    2008-12-01

    Boron neutron capture therapy (BNCT) is a promising binary modality used to treat malignant brain gliomas. To optimize BNCT effectiveness a non-invasive method is needed to monitor the spatial distribution of BNCT carriers in order to estimate the optimal timing for neutron irradiation. In this study, in vivo spatial distribution mapping and pharmacokinetics evaluation of the (19)F-labelled boronophenylalanine (BPA) were performed using (19)F magnetic resonance imaging ((19)F MRI) and (19)F magnetic resonance spectroscopy ((19)F MRS). Characteristic uptake of (19)F-BPA in C6 glioma showed a maximum at 2.5 h after compound infusion as confirmed by both (19)F images and (19)F spectra acquired on blood samples collected at different times after infusion. This study shows the ability of (19)F MRI to selectively map the bio-distribution of (19)F-BPA in a C6 rat glioma model, as well as providing a useful method to perform pharmacokinetics of BNCT carriers. PMID:19001698

  15. 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

    2006-03-01

    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.

  16. Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.

    PubMed

    Giladi, Moshe; Weinberg, Uri; Schneiderman, Rosa S; Porat, Yaara; Munster, Michal; Voloshin, Tali; Blatt, Roni; Cahal, Shay; Itzhaki, Aviran; Onn, Amir; Kirson, Eilon D; Palti, Yoram

    2014-10-01

    Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Common treatment modalities for NSCLC include surgery, radiotherapy, chemotherapy, and, in recent years, the clinical management paradigm has evolved with the advent of targeted therapies. Despite such advances, the impact of systemic therapies for advanced disease remains modest, and as such, the prognosis for patients with NSCLC remains poor. Standard modalities are not without their respective toxicities and there is a clear need to improve both efficacy and safety for current management approaches. Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death. We evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. We investigated the response of Lewis lung carcinoma and KLN205 squamous cell carcinoma in mice treated with TTFields in combination with pemetrexed, cisplatin, or paclitaxel and compared these to the efficacy observed in mice exposed only to the single agents. Combining TTFields with these therapeutic agents enhanced treatment efficacy in comparison with the respective single agents and control groups in all animal models. Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC.

  17. Magnetic nanoparticles with high specific absorption rate of electromagnetic energy at low field strength for hyperthermia therapy

    PubMed Central

    Stigliano, Robert; Baker, Ian

    2015-01-01

    Magnetic nanoparticles (MNPs), referred to as the Dartmouth MNPs, which exhibit high specific absorption rate at low applied field strength have been developed for hyperthermia therapy applications. The MNPs consist of small (2–5 nm) single crystals of gamma-Fe2O3 with saccharide chains implanted in their crystalline structure, forming 20–40 nm flower-like aggregates with a hydrodynamic diameter of 110–120 nm. The MNPs form stable (>12 months) colloidal solutions in water and exhibit no hysteresis under an applied quasistatic magnetic field, and produce a significant amount of heat at field strengths as low as 100 Oe at 99–164 kHz. The MNP heating mechanisms under an alternating magnetic field (AMF) are discussed and analyzed quantitatively based on (a) the calculated multi-scale MNP interactions obtained using a three dimensional numerical model called the method of auxiliary sources, (b) measured MNP frequency spectra, and (c) quantified MNP friction losses based on magneto-viscous theory. The frequency responses and hysteresis curves of the Dartmouth MNPs are measured and compared to the modeled data. The specific absorption rate of the particles is measured at various AMF strengths and frequencies, and compared to commercially available MNPs. The comparisons demonstrate the superior heating properties of the Dartmouth MNPs at low field strengths (<250 Oe). This may extend MNP hyperthermia therapy to deeper tumors that were previously non-viable targets, potentially enabling the treatment of some of the most difficult cancers, such as pancreatic and rectal cancers, without damaging normal tissue. PMID:25825545

  18. Magnetic nanoparticles with high specific absorption rate of electromagnetic energy at low field strength for hyperthermia therapy

    NASA Astrophysics Data System (ADS)

    Shubitidze, Fridon; Kekalo, Katsiaryna; Stigliano, Robert; Baker, Ian

    2015-03-01

    Magnetic nanoparticles (MNPs), referred to as the Dartmouth MNPs, which exhibit high specific absorption rate at low applied field strength have been developed for hyperthermia therapy applications. The MNPs consist of small (2-5 nm) single crystals of gamma-Fe2O3 with saccharide chains implanted in their crystalline structure, forming 20-40 nm flower-like aggregates with a hydrodynamic diameter of 110-120 nm. The MNPs form stable (>12 months) colloidal solutions in water and exhibit no hysteresis under an applied quasistatic magnetic field, and produce a significant amount of heat at field strengths as low as 100 Oe at 99-164 kHz. The MNP heating mechanisms under an alternating magnetic field (AMF) are discussed and analyzed quantitatively based on (a) the calculated multi-scale MNP interactions obtained using a three dimensional numerical model called the method of auxiliary sources, (b) measured MNP frequency spectra, and (c) quantified MNP friction losses based on magneto-viscous theory. The frequency responses and hysteresis curves of the Dartmouth MNPs are measured and compared to the modeled data. The specific absorption rate of the particles is measured at various AMF strengths and frequencies, and compared to commercially available MNPs. The comparisons demonstrate the superior heating properties of the Dartmouth MNPs at low field strengths (<250 Oe). This may extend MNP hyperthermia therapy to deeper tumors that were previously non-viable targets, potentially enabling the treatment of some of the most difficult cancers, such as pancreatic and rectal cancers, without damaging normal tissue.

  19. Evaluation of Breast Sentinel Lymph Node Coverage by Standard Radiation Therapy Fields

    SciTech Connect

    Rabinovitch, Rachel Ballonoff, Ari; Newman, Francis M.S.; Finlayson, Christina

    2008-04-01

    Background: Biopsy of the breast sentinel lymph node (SLN) is now a standard staging procedure for early-stage invasive breast cancer. The anatomic location of the breast SLN and its relationship to standard radiation fields has not been described. Methods and Materials: A retrospective review of radiotherapy treatment planning data sets was performed in patients with breast cancer who had undergone SLN biopsy, and those with a surgical clip at the SLN biopsy site were identified. The location of the clip was evaluated relative to vertebral body level on an anterior-posterior digitally reconstructed radiograph, treated whole-breast tangential radiation fields, and standard axillary fields in 106 data sets meeting these criteria. Results: The breast SLN varied in vertebral body level position, ranging from T2 to T7 but most commonly opposite T4. The SLN clip was located below the base of the clavicle in 90%, and hence would be excluded from standard axillary radiotherapy fields where the inferior border is placed at this level. The clip was within the irradiated whole-breast tangent fields in 78%, beneath the superior-posterior corner multileaf collimators in 12%, and outside the tangent field borders in 10%. Conclusions: Standard axillary fields do not encompass the lymph nodes at highest risk of containing tumor in breast cancer patients. Elimination of the superior-posterior corner MLCs from the tangent field design would result in inclusion of the breast SLN in 90% of patients treated with standard whole-breast irradiation.

  20. Video Screen Capture Basics

    ERIC Educational Resources Information Center

    Dunbar, Laura

    2014-01-01

    This article is an introduction to video screen capture. Basic information of two software programs, QuickTime for Mac and BlueBerry Flashback Express for PC, are also discussed. Practical applications for video screen capture are given.

  1. Risk of Developing Second Cancer From Neutron Dose in Proton Therapy as Function of Field Characteristics, Organ, and Patient Age

    SciTech Connect

    Zacharatou Jarlskog, Christina; Paganetti, Harald

    2008-09-01

    Purpose: To estimate the risk of a second malignancy after treatment of a primary brain cancer using passive scattered proton beam therapy. The focus was on the cancer risk caused by neutrons outside the treatment volume and the dependency on the patient's age. Methods and Materials: Organ-specific neutron-equivalent doses previously calculated for eight different proton therapy brain fields were considered. Organ-specific models were applied to assess the risk of developing solid cancers and leukemia. Results: The main contributors (>80%) to the neutron-induced risk are neutrons generated in the treatment head. Treatment volume can influence the risk by up to a factor of {approx}2. Young patients are subject to significantly greater risks than are adult patients because of the geometric differences and age dependency of the risk models. Breast cancer should be the main concern for females. For males, the risks of lung cancer, leukemia, and thyroid cancer were significant for pediatric patients. In contrast, leukemia was the leading risk for an adult. Most lifetime risks were <1% (70-Gy treatment). The only exceptions were breast, thyroid, and lung cancer for females. For female thyroid cancer, the treatment risk can exceed the baseline risk. Conclusion: The risk of developing a second malignancy from neutrons from proton beam therapy of a brain lesion is small (i.e., presumably outweighed by the therapeutic benefit) but not negligible (i.e., potentially greater than the baseline risk). The patient's age at treatment plays a major role.

  2. Regional electric field induced by electroconvulsive therapy in a realistic finite element head model: Influence of white matter anisotropic conductivity

    PubMed Central

    Lee, Won Hee; Deng, Zhi-De; Kim, Tae-Seong; Laine, Andrew F.; Lisanby, Sarah H.; Peterchev, Angel V.

    2012-01-01

    We present the first computational study investigating the electric field (E-field) strength generated by various electroconvulsive therapy (ECT) electrode configurations in specific brain regions of interest (ROIs) that have putative roles in the therapeutic action and/or adverse side effects of ECT. This study also characterizes the impact of the white matter (WM) conductivity anisotropy on the E-field distribution. A finite element head model incorporating tissue heterogeneity and WM anisotropic conductivity was constructed based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. We computed the spatial E-field distributions generated by three standard ECT electrode placements including bilateral (BL), bifrontal (BF), and right unilateral (RUL) and an investigational electrode configuration for focal electrically administered seizure therapy (FEAST). The key results are that (1) the median E-field strength over the whole brain is 3.9, 1.5, 2.3, and 2.6 V/cm for the BL, BF, RUL, and FEAST electrode configurations, respectively, which coupled with the broad spread of the BL E-field suggests a biophysical basis for observations of superior efficacy of BL ECT compared to BF and RUL ECT; (2) in the hippocampi, BL ECT produces a median E-field of 4.8 V/cm that is 1.5–2.8 times stronger than that for the other electrode configurations, consistent with the more pronounced amnestic effects of BL ECT; and (3) neglecting the WM conductivity anisotropy results in E-field strength error up to 18% overall and up to 39% in specific ROIs, motivating the inclusion of the WM conductivity anisotropy in accurate head models. This computational study demonstrates how the realistic finite element head model incorporating tissue conductivity anisotropy provides quantitative insight into the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation

  3. 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

  4. 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 Central

    Chandra, S.; Ahmad, T.; Barth, R. F.; Kabalka, G. W.

    2014-01-01

    Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron-10 (10B) atoms to individual tumor cells. Cell killing results from the 10B (n, α)7Li neutron capture and fission reactions that occur if a sufficient number of 10B atoms are localized in the tumor cells. Intranuclear 10B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of 10B atoms reflects both bound and free pools of boron in individual tumor 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 PET and MRI. In this study, secondary ion mass spectrometry (SIMS) 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 tumors 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 tumor 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 suggests that it might be advantageous if patients were placed on a

  5. Optimized Nanosecond Pulsed Electric Field Therapy Can Cause Murine Malignant Melanomas to Self-Destruct with a Single Treatment

    PubMed Central

    Nuccitelli, Richard; Tran, Kevin; Sheikh, Saleh; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela

    2010-01-01

    We have identified a new, nanosecond pulsed electric field (nsPEF) therapy capable of eliminating murine melanomas located in the skin with a single treatment. When these optimized parameters are used, nsPEFs initiate apoptosis without hyperthermia. We have developed new suction electrodes that are compatible with human skin and have applied them to a xenograft nude mouse melanoma model system to identify the optimal field strength, pulse frequency and pulse number for the treatment of murine melanomas. A single treatment using the optimal pulse parameters (2000 pulses, 100 ns in duration, 30 kV/cm in amplitude at a pulse frequency of 5–7 pulses/s) eliminated all 17 melanomas treated with those parameters in 4 mice. This was the highest pulse frequency that we could use without raising the treated skin tumor temperature above 40 °C. We also demonstrate that the effects of nsPEF therapy are highly localized to only cells located between electrodes and results in very little scarring of the nsPEF-treated skin. PMID:20473857

  6. Faculty Perception of and Resistance to Online Education in the Fields of Acupuncture, Chiropractic, and Massage Therapy

    PubMed Central

    Schwartz, Jan

    2010-01-01

    This paper reports findings of a research study undertaken to determine the attitudes and perceptions of acupuncture, chiropractic, and massage therapy faculty with regard to online learning within their respective disciplines, and to determine how they might be persuaded to teach online. The study surveyed faculty teaching at schools in these three fields and followed up with additional interviews. The study results indicate that, in general, acupuncture, chiropractic, and massage therapy faculty lack awareness of the capabilities of online education and the elements of good online learning. There is also a perception that what they teach cannot be taught online because of its kinesthetic requirements. The faculty hold this perception in spite of the success of medical science and related health care fields in the online environment, and they do not seem to separate the kinesthetic from the didactic. The present study indicates that faculty opinions about online instruction in this alternative type of education range from being willing to look at the potential of online education to outright dismissing it. PMID:21589712

  7. Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field

    PubMed Central

    Yi, Xiaomin; Wang, Fuli; Qin, Weijun; Yang, Xiaojian; Yuan, Jianlin

    2014-01-01

    Near-infrared fluorescence (NIRF) imaging is an attractive modality for early cancer detection with high sensitivity and multi-detection capability. Due to convenient modification by conjugating with moieties of interests, NIRF probes are ideal candidates for cancer targeted imaging. Additionally, the combinatory application of NIRF imaging and other imaging modalities that can delineate anatomical structures extends fluorometric determination of biomedical information. Moreover, nanoparticles loaded with NIRF dyes and anticancer agents contribute to the synergistic management of cancer, which integrates the advantage of imaging and therapeutic functions to achieve the ultimate goal of simultaneous diagnosis and treatment. Appropriate probe design with targeting moieties can retain the original properties of NIRF and pharmacokinetics. In recent years, great efforts have been made to develop new NIRF probes with better photostability and strong fluorescence emission, leading to the discovery of numerous novel NIRF probes with fine photophysical properties. Some of these probes exhibit tumoricidal activities upon light radiation, which holds great promise in photothermal therapy, photodynamic therapy, and photoimmunotherapy. This review aims to provide a timely and concise update on emerging NIRF dyes and multifunctional agents. Their potential uses as agents for cancer specific imaging, lymph node mapping, and therapeutics are included. Recent advances of NIRF dyes in clinical use are also summarized. PMID:24648733

  8. Capturing carbon and saving coal

    SciTech Connect

    Johnson, J.

    2007-10-15

    Electric utilities face a tangle of choices when figuring how to pull CO{sub 2} from coal-fired plants. The article explains the three basic approaches to capturing CO{sub 2} - post-combustion, oxyfuel combustion and pre-combustion. Researchers at US DOE labs and utilities are investigating new solvents that capture CO{sub 2} more efficiently than amines and take less energy. Ammonium carbonate has been identified by EPRI as one suitable solvent. Field research projects on this are underway in the USA. Oxyfuel combustion trials are also being planned. Pre-combustion, or gasification is a completely different way of pulling energy from coal and, for electricity generation, this means IGCC systems. AEP, Southern Cinergy and Xcel are considering IGCC plants but none will capture CO{sub 2}. Rio Tinto and BP are planning a 500 MW facility to gasify coke waste from petroleum refining and collect and sequester CO{sub 2}. However, TECO recently dropped a project to build a 789 MW IGCC coal fired plant even though it was to receive a tax credit to encourage advanced coal technologies. The plant would not have captured CO{sub 2}. The company said that 'with uncertainty of carbon capture and sequestration regulations being discussed at the federal and state levels, the timing was not right'. 4 figs.

  9. High-throughput phenotyping (HTP) identifies seedling root traits linked to variation in seed yield and nutrient capture in field-grown oilseed rape (Brassica napus L.)

    PubMed Central

    Thomas, C. L.; Graham, N. S.; Hayden, R.; Meacham, M. C.; Neugebauer, K.; Nightingale, M.; Dupuy, L. X.; Hammond, J. P.; White, P. J.; Broadley, M. R.

    2016-01-01

    Background and Aims Root traits can be selected for crop improvement. Techniques such as soil excavations can be used to screen root traits in the field, but are limited to genotypes that are well-adapted to field conditions. The aim of this study was to compare a low-cost, high-throughput root phenotyping (HTP) technique in a controlled environment with field performance, using oilseed rape (OSR; Brassica napus) varieties. Methods Primary root length (PRL), lateral root length and lateral root density (LRD) were measured on 14-d-old seedlings of elite OSR varieties (n = 32) using a ‘pouch and wick’ HTP system (∼40 replicates). Six field experiments were conducted using the same varieties at two UK sites each year for 3 years. Plants were excavated at the 6- to 8-leaf stage for general vigour assessments of roots and shoots in all six experiments, and final seed yield was determined. Leaves were sampled for mineral composition from one of the field experiments. Key Results Seedling PRL in the HTP system correlated with seed yield in four out of six (r = 0·50, 0·50, 0·33, 0·49; P < 0·05) and with emergence in three out of five (r = 0·59, 0·22, 0·49; P < 0·05) field experiments. Seedling LRD correlated positively with leaf concentrations of some minerals, e.g. calcium (r = 0·46; P < 0·01) and zinc (r = 0·58; P < 0·001), but did not correlate with emergence, general early vigour or yield in the field. Conclusions Associations between PRL and field performance are generally related to early vigour. These root traits might therefore be of limited additional selection value, given that vigour can be measured easily on shoots/canopies. In contrast, LRD cannot be assessed easily in the field and, if LRD can improve nutrient uptake, then it may be possible to use HTP systems to screen this trait in both elite and more genetically diverse, non-field-adapted OSR. PMID:27052342

  10. Capture Their Attention: Capturing Lessons Using Screen Capture Software

    ERIC Educational Resources Information Center

    Drumheller, Kristina; Lawler, Gregg

    2011-01-01

    When students miss classes for university activities such as athletic and academic events, they inevitably miss important class material. Students can get notes from their peers or visit professors to find out what they missed, but when students miss new and challenging material these steps are sometimes not enough. Screen capture and recording…

  11. Cryogenic Carbon Capture

    SciTech Connect

    2010-07-15

    IMPACCT Project: SES is developing a process to capture CO2 from the exhaust gas of coal-fired power plants by desublimation - the conversion of a gas to a solid. Capturing CO2 as a solid and delivering it as a liquid avoids the large energy cost of CO2 gas compression. SES’ capture technology facilitates the prudent use of available energy resources. Coal is our most abundant energy resource and is an excellent fuel for baseline power production. SES capture technology can capture 99% of the CO2 emissions in addition to a wide range of other pollutants more efficiently and at lower costs than existing capture technologies. SES’ capture technology can be readily added to our existing energy infrastructure.

  12. 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

    2014-10-01

    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.

  13. 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.

  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

    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.

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

    PubMed

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

    2006-06-01

    The characteristics of moderator assembly dimension are investigated for the usage of 7Li(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 D2O 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 s