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Sample records for boron neutron-capture therapy

  1. Spectral tailoring for boron Neutron capture therapy

    NARCIS (Netherlands)

    Nievaart, V.A.

    2007-01-01

    In several places in the world, such as Petten and Delft in the Netherlands, investigations are in progress in the fight against certain types of cancer with Boron Neutron Capture Therapy. The basic idea is very simple: boron is loaded only into the cancer cells, using a special drug, after which

  2. Clinical aspects of boron neutron capture therapy

    International Nuclear Information System (INIS)

    Goodman, J.H.; Gahbauer, R.; Clendenon, N.

    1986-01-01

    Boron neutron capture therapy is potentially useful in treating malignant tumors of the central nervous system and is technically possible. Additional in vitro and in vivo testing is required to determine toxicities, normal tissue tolerances and tissue responses to treatment parameters. Adequate tumor uptake of the capture agent can be evaluated clinically prior to implementation of a finalized treatment protocol. Phase I and Phase II protocol development, clinical pharmacokinetic studies and neutron beam development

  3. Spectromicroscopy in Boron Neutron Capture Therapy Research

    Science.gov (United States)

    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.

  4. Accelerator-driven boron neutron capture therapy

    Science.gov (United States)

    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.

  5. Microdosimetry for Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Maughan, R.L.; Kota, C.

    2000-01-01

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

  6. Considerations for boron neutron capture therapy studies

    International Nuclear Information System (INIS)

    Faria Gaspar, P. de.

    1994-01-01

    Radiotherapy is indispensable as a mean to eradicate deeply or infiltrating tumor tissue that can not be removed surgically. Therefore, it is not selective and may also kill the surrounding health tissue. The principle of BNCT (Boron Neutron Capture Therapy) consist in targeting a tumor selectively with a boron-10 compound. This nuclide has a large capture cross section for thermal neutrons and the nuclear reaction and the delivered energy in locus will selective the tumor. Since its initial proposal in 1963 BNCT has made much progress, however it is not used in a routine treatment. In this work it was approached some complex procedures, as the obtention of selective boron compounds, the adequate set up of neutron beams, the biodistribution, the in vivo and in vitro studies, and also human patients treatments. This work provide fundamentals about BNCT to professional of different areas of knowledge since it comprises multidisciplinary study. It includes appendixes for the ones not related to the field for a better comprehension of the many aspects involved. It is also presented a glossary containing technical and basic aspects involved. It is also presented a glossary containing technical and basic terms referred in the work. (author). 174 refs, 1 fig, 12 apps

  7. Anesthetic management of Boron Neutron Capture Therapy for glioblastoma

    International Nuclear Information System (INIS)

    Shinomura, T.; Furutani, H.; Osawa, M.; Ono, K.; Fukuda, K.

    2000-01-01

    General anesthesia was given to twenty-seven patients who received Boron Neutron Capture Therapy (BNCT) under craniotomy at Kyoto University Research Reactor from 1991 to 1999. Special considerations are required for anesthesia. (author)

  8. Anesthetic management of Boron Neutron Capture Therapy for glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Shinomura, T.; Furutani, H.; Osawa, M.; Ono, K.; Fukuda, K. [Kyoto Univ. (Japan)

    2000-10-01

    General anesthesia was given to twenty-seven patients who received Boron Neutron Capture Therapy (BNCT) under craniotomy at Kyoto University Research Reactor from 1991 to 1999. Special considerations are required for anesthesia. (author)

  9. Neutron dosimetry in boron neutron capture therapy

    International Nuclear Information System (INIS)

    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 2 B 12 H 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 10 B in boron containing cells through the 10 B(n,α) 7 Li reaction producing charged particles with a maximum range of approx. 10μm 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 6 Li and 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 14 N(n,p) 14 C reaction. Measurements of thermal flux were compared with calculations and with measurements done with activation foils

  10. Role of gel dosimeters in boron neutron capture therapy

    International Nuclear Information System (INIS)

    Khajeali, Azim; Farajollahi, Ali Reza; Khodadadi, Roghayeh; Kasesaz, Yaser; Khalili, Assef

    2015-01-01

    Gel dosimeters have acquired a unique status in radiotherapy, especially with the advent of the new techniques in which there is a need for three-dimensional dose measurement with high spatial resolution. One of the techniques in which the use of gel dosimeters has drawn the attention of the researchers is the boron neutron capture therapy. Exploring the history of gel dosimeters, this paper sets out to study their role in the boron neutron capture therapy dosimetric process. - Highlights: • Gel dosimeters have been investigated. • Conventional dosimetric proses of BNCT has been investigated. • Role of gel dosimeters in BNCT has been investigated

  11. Future boronated molecules for neutron capture therapy

    International Nuclear Information System (INIS)

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

    1986-01-01

    The ability of several boron compounds to localize in tumor cells is examined. A number of first and second generation compounds which were not synthesized specifically for localization are described. Among these are the boron hydrides and boranes. A third generation of boron compounds are designed for selective localization. These fall into two groups: relatively small organic compounds and boronated antibodies, both of which are discussed here

  12. Boron-containing thioureas for neutron capture therapy

    International Nuclear Information System (INIS)

    Ketz, H.

    1993-01-01

    Melanin is produced in large amounts in malignant melanotic melanomas. Because thiourea compounds are covalently incorporated into melanin during its biosynthesis, the preparation of boronated thiourea-derivatives is of particular interest for the BNCT (Boron Neutron Capture Therapy). Accumulation of boron in tumors by means of boronated thiourea-derivatives may therefore provide levels of 10 B which are useful for BNCT. In BNCT the tumor containing the boron compound is irradiated with epithermal neutrons to generate He- and Li-nuclei from the 10 B which can then destroy the tumor cells. Because of the short ranges of these particles (approximately one cell diameter) the damage will be almost exclusively confined to the tumor leaving normal tissue unharmed. High accumulation of 2-mercapto-1-methylimidazole (methimazole) in melanotic melanomas has been described in the literature. Boronated derivatives of methimazole were therefore synthesized. Boron was in the form of a boronic acid, a nido-carbonate and a mercaptoundeca hydro-closo-dodecaborate (BSH). The synthesis of the boron cluster derivatives of methimazole (nido-carborate- and BSH-derivatives) with 9 resp. 12 boron atoms in the molecule were expected to achieve higher concentrations of boron in the tumor than in the case of the boronic acid compound with its single boron atom. (orig.) [de

  13. Boron neutron capture therapy: Brain Tumor Treatment Evaluation Program

    International Nuclear Information System (INIS)

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

    1988-01-01

    The United States (US) Department of Energy (DOE) recently initiated a focused, multidisciplined program to evaluate Boron Neutron Capture Therapy (BNCT) for the treatment of brain tumors. The program, centered at the DOE/endash/Idaho National Engineering Laboratory (INEL), will develop the analytical, diagnostic and treatment tools, and the database required for BNCT technical assessment. The integrated technology will be evaluated in a spontaneously-occurring canine brain-tumor model. Successful animal studies are expected to lead to human clinical trials within four to five years. 2 refs., 3 figs

  14. Experience of boron neutron capture therapy in Japan

    International Nuclear Information System (INIS)

    Kanda, K.

    2004-01-01

    Four research reactors are currently licensed for medical application in Japan. As of July 1995, approximately 210 clinical irradiations using these research reactors have been done for brain and skin tumors as shown. The number of chief medical doctors certified by the Government is eleven so far. Among them, eight doctors have already treated tumor patients using the Kyoto University Reactor (KUR, 5MW). Recently in USA clinical trials have been restarted using epithermal neutrons at MIT and BNL. In this paper, the experience of clinical trials of boron neutron capture therapy (BNCT) which have been performed in Japan, mainly physics studies, are reviewed, and current studies are also introduced

  15. Commissioning of accelerator based boron neutron capture therapy system

    International Nuclear Information System (INIS)

    Nakamura, S.; Wakita, A.; Okamoto, H.; Igaki, H.; Itami, J.; Ito, M.; Abe, Y.; Imahori, Y.

    2017-01-01

    Boron neutron capture therapy (BNCT) is a treatment method using a nuclear reaction of 10 B(n, α) 7 Li. BNCT can be deposited the energy to a tumor since the 10 B which has a higher cross-section to a neutron is high is concentrated on the tumor. It is different from conventional radiation therapies that BNCT expects higher treatment effect to radiation resistant tumors since the generated alpha and lithium particles have higher radiological biological effectiveness. In general, BNCT has been performed in research nuclear reactor. Thus, BNCT is not widely applied in a clinical use. According to recent development of accelerator-based boron neutron capture therapy system, the system has an adequate flux of neutrons. Therefore, National Cancer Canter Hospital, Tokyo, Japan is planning to install accelerator based BNCT system. Protons with 2.5 MeV are irradiated to a lithium target system to generate neutrons. As a result, thermal load of the target is 50 kW since current of the protons is 20.0 mA. Additionally, when the accelerator-based BNCT system is installed in a hospital, the facility size is disadvantage in term of neutron measurements. Therefore, the commissioning of the BNCT system is being performed carefully. In this article, we report about the commissioning. (author)

  16. Proceedings of workshop on 'Boron Chemistry and Boron Neutron Capture Therapy'

    International Nuclear Information System (INIS)

    Kitaoka, Y.

    1991-07-01

    This volume contains the proceedings of the 3rd Workshop on 'the Boron Chemistry and Boron Neutron Capture Therapy' held on February 12, in 1991. In this workshop, our attention was focused on the chemical nature of boron compounds and the boron neutron capture therapy (BNCT). First, clinical experiences of BNCT in KURRI in 1990 and 1991 were reported (Chap. 3). The feasibility of the gadolinium neutron capture therapy for brain tumors was discussed (Chap. 4). In the chemical field, a rapid spectrophotometric determination of trace amounts of borons in biological samples is described (Chap. 5). The chemical behaviours of p-boronophenylalanine and its analogs in aqueous solutions were investigated by a paper electrophoresis and infrared spectroscopy (Chap. 6). On the molecular design and synthesis of new boron carriers for BNCT, several new synthetic methods for B-10 containing nucleoside derivatives were shown (Chap. 7). (author)

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

    International Nuclear Information System (INIS)

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

    1999-01-01

    Boron Neutron Capture Therapy [BNCT] is a binary method of cancer therapy based on the capture of neutrons by a boron-10 atom [ 10 B]. Cytotoxic 7 Li nuclei and α-particles are emitted, with a range in tissue of 9 and 5 microm, respectively, about one cell diameter. The major obstacle to clinically viable BNCT is the selective localization of 5-30 ppm 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

  18. Physical engineering and medical physics on boron neutron capture therapy

    International Nuclear Information System (INIS)

    Sakurai, Yoshinori

    2011-01-01

    The contents of physical engineering and medical physics that support boron neutron capture therapy (BNCT) can be roughly classified to the four items, (1) neutron irradiation system, (2) development and improvement of dose assessment techniques, (3) development and improvement of dose planning system, and (4) quality assurance and quality control. This paper introduces the BNCT at Kyoto University Research Reactor Institute, with a focus on the basic physics of BNCT, thermal neutron irradiation and epithermal neutron irradiation, heavy water neutron irradiation facilities of KUR, and medical irradiation system of KUR. It also introduces the world's first BNCT clinical cyclotron irradiation system (C-BENS) of Kyoto University Research Reactor Institute, BNCT dose assessment techniques, dose planning system, and quality assurance and quality control. (A.O.)

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

    International Nuclear Information System (INIS)

    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 9 n/cm 2 /sec) may be measured because of this potentially high count rate and the small diameter of the fiber

  20. The Swedish facility for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Skoeld, K.; Capala, J.; Kierkegaard, J.; Haakansson, R.; Gudowska, I.

    2000-01-01

    A BNCT (Boron Neutron Capture Therapy) facility has been constructed at the R2-0 reactor at Studsvik, Sweden. R2-0 is a 1 MW, open core, pool reactor. The reactor core is suspended on a movable tower and can be positioned anywhere in the pool. The BNCT facility includes two adjacent, parallel filter/moderator configurations and the reactor core is positioned in front of any of them as appropriate. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range and with an extended collimator for convenient patient positioning. The other beam has been designed for radiobiological research and is equipped with a heavy water moderator and a large irradiation cavity with a uniform field of thermal neutrons. (author)

  1. Proceedings of workshop on 'boron science and boron neutron capture therapy'

    Energy Technology Data Exchange (ETDEWEB)

    Kitaoka, Y. [ed.

    1998-12-01

    This volume contains the abstracts and programs of the 8th (1996), 9th (1997) and 10th (1998) of the workshop on 'the Boron Science and Boron Neutron Capture Therapy' and the recent progress reports especially subscribed. The 11 of the presented papers are indexed individually. (J.P.N.)

  2. Experimental boron neutron capture therapy for melanoma: Systemic delivery of boron to melanotic and amelanotic melanoma

    International Nuclear Information System (INIS)

    Coderre, J.A.; Glass, J.D.; Micca, P.; Greenberg, D.; Packer, S.

    1990-01-01

    The boron-containing melanin precursor analogue p-boronophenylalanine (BPA) has previously been shown to selectively deliver boron to pigmented murine melanomas when administered in a single intragastric dose. If boron neutron capture therapy is to become a clinically useful method of radiation therapy for human malignant melanoma, the boron carrier must be capable of delivering useful amounts of boron to remote tumor sites (metastases) and to poorly pigmented melanomas. The authors have now determined the ability of BPA to accumulate in several nonpigmented melanoma models including human melanoma xenografts in nude mice. The absolute amount of boron in the nonpigmented melanomas was about 50% of the observed in the pigmented counterparts but was still selectively concentrated in the tumor relative to normal tissues in amounts sufficient for effective neutron capture therapy. Single intragastric doses of BPA resulted in selective localization of boron in the amelanotic Greene melanoma carried in the anterior chamber of the rabbit eye and in a pigmented murine melanoma growing in the lungs. The ratio of the boron concentration in these tumors to the boron concentration in the immediately adjacent normal tissue was in the range of 3:1 to 4:1. These distribution studies support the proposal that boron neutron capture therapy may be useful as a regional therapy for malignant melanoma

  3. Neutron spectrum for neutron capture therapy in boron

    International Nuclear Information System (INIS)

    Medina C, D.; Soto B, T. G.; Baltazar R, A.; Vega C, H. R.

    2016-10-01

    Glioblastoma multiforme is the most common and aggressive of brain tumors and is difficult to treat by surgery, chemotherapy or conventional radiation therapy. One treatment alternative is the Neutron Capture Therapy in Boron, which requires a beam modulated in neutron energy and a drug with 10 B able to be fixed in the tumor. When the patients head is exposed to the neutron beam, they are captured by the 10 B and produce a nucleus of 7 Li and an alpha particle whose energy is deposited in the cancer cells causing it to be destroyed without damaging the normal tissue. One of the problems associated with this therapy is to have an epithermal neutrons flux of the order of 10 9 n/cm 2 -sec, whereby irradiation channels of a nuclear research reactor are used. In this work using Monte Carlo methods, the neutron spectra obtained in the radial irradiation channel of the TRIGA Mark III reactor are calculated when inserting filters whose position and thickness have been modified. From the arrangements studied, we found that the Fe-Cd-Al-Cd polyethylene filter yielded a ratio between thermal and epithermal neutron fluxes of 0.006 that exceeded the recommended value (<0.05), and the dose due to the capture gamma rays is lower than the dose obtained with the other arrangements studied. (Author)

  4. The radiation biology of Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Coderre, J.A.

    2003-01-01

    Boron Neutron Capture Therapy (BNCT) produces a complex mixture of high and low-LET radiations in tissue. Using data on the biological effectiveness of these various dose components, derived primarily in small animals irradiated with thermal neutrons, it has been possible to express clinical BNCT doses in photon-equivalent units. The accuracy of these calculated doses in normal tissue and tumor will be reviewed. Clinical trials are underway at a number of centers. There are differences in the neutron beams at these centers, and differences in the details of the clinical protocols. Ideally, data from all centers using similar boron compounds and treatment protocols should be compared and combined, if appropriate, in a multi-institutional study in order to strengthen statistical analysis. An international dosimetry exchange is underway that will allow the physical doses from the various treatment centers to be quantitatively compared. As a first step towards the comparison of the clinical data, the normal brain tolerance data from the patients treated in the initial Brookhaven National Laboratory and the Harvard/MIT BNCT clinical trials have been compared. The data provide a good estimate of the normal brain tolerance for a somnolence syndrome endpoint, and provide guidance for setting normal brain tolerance limits in ongoing and future clinical trials. Escalation of the dose in BNCT can be accomplished by increasing the amount of the boron compound administered, increasing the duration of the neutron exposure, or both. The dose escalations that have been carried out to date at the various treatment centers will be compared and contrasted. Possible future clinical trials using BNCT in combination with other modalities will be discussed

  5. A colorimetric determination of boron in biological sample for boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    Camillo, M.A.P.; Tomac Junior, U.

    1990-01-01

    The boron neutron capture therapy (BNCT) has shown better prognosis in the treatment of glyemas and gluoblastomas grade III and IV than other therapies. During the treatment the levels of Na 2 10 B 12 H 11 SH must be known in several compartiments of the organism and with this purpose the method of colorimetric determination of boron using curcumine was established. This method is simple, reprodutible and adequate sensitivity for this control. (author) [pt

  6. A colorimetric determination of boron in biological sample for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Camilo, M.A.P.; Tomac Junior, U.

    1989-01-01

    The boron neutron capture therapy (BNCT) has shown better prognosis in the treatment of gliomas and glioblastomas grade III and IV than other therapies. During the treatment of levels of Na 2 10 B 12 H 11 S H must be known in several compartments of the organism and with this purpose the method of colorimetric determination of boron using curcumin was established. This method is simples, reproducible and has adequate sensitivity for this control. (author). 7 refs, 3 figs, 1 tab

  7. Materials for neutron beam optimization for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Matsumoto, Tetsuo

    2001-01-01

    Several prospective materials (neutron filter/moderator, beam reflector, gamma ray shielding and beam collimator) were studied with a view to generating thermal and epithermal neutron beams suited for boron neutron capture therapy (BNCT). The beams are delivered from the thermal and thermalizing column exits situated on two opposite faces of a TRIGA-II type reactor. An investigation was performed with Monte Carlo calculations from a viewpoint of obtaining sufficiently intense thermal and epithermal neutron beams separately, and little adulterated both with neutrons of extraneous energy ranges and with gamma rays. High-density graphite (G) would be the most suitable material for thermal neutron beams as a neutron filter/moderator, and the combination of aluminum (Al) and aluminum fluoride (AlF 3 ) for epithermal neutron beams. The graphite would be also the most promising material for thermal neutron beams as a beam reflector while for epithermal neutron beams the choice would be lead fluoride (PbF 2 ). The PbF 2 would be also the most suitable material for epithermal neutron beams as a gamma ray shielding, and bismuth (Bi) for thermal neutron beam. The PbF 2 would be also the most useful material for epithermal neutron beam as a beam collimator while for thermal neutron beam the choice would be the graphite. The epithermal neutron beam for BNCT could be optimized with the progressive use of PbF 2 . (author)

  8. Boron neutron capture therapy for recurrent head and neck malignancies

    International Nuclear Information System (INIS)

    Kato, Itsuro; Ono, Koji; Sakurai, Yoshinori

    2006-01-01

    To avoid severe impairment of oro-facial structures and functions, it is necessary to explore new treatments for recurrent head and neck malignancies (HNM). Boron neutron capture therapy (BNCT) is tumor-cell targeted radiotherapy that has significant superiority over conventional radiotherapies in principle. So far for 4 years and 3 months, we have treated with 37 times of BNCT for 21 patients (14 squamous cell carcinomas (SCC), 4 salivary gland carcinomas and 3 sarcomas) with a recurrent and far advanced HNM since 2001. Results are (1) 10 B concentration of tumor/normal tissue ratio (T/N ratio) of FBPA-PET studies were SCC: 1.8-5.7, sarcoma: 2.5-4.0, parotid tumor: 2.5-3.7. (2) Therapeutic effects were CR: 6cases, PR: 11cases, PD: 3cases NE (not evaluated): 1case. Response rate was 81%. (3) Improvement of QOL such as a relief of severe pain, bleeding, and exudates at the local lesion, improvement of PS, disappearance of ulceration, covered with normal skin and preserved oral and maxillofacial functions and tissues. (4) Survival periods after BNCT were 1-51 months (mean: 9.8 months). 4-year survival rate was 39% by Kaplan-Meier analysis. (5) A few adverse-effects such as transient mucositis, alopecia were recognized. These results indicate that BNCT represents a new and promising treatment approach for advanced HNM. (author)

  9. Current status of accelerator-based boron neutron capture therapy

    International Nuclear Information System (INIS)

    Kreiner, A. J.; Bergueiro, J.; Di Paolo, H.; Castell, W.; Vento, V. Thatar; Cartelli, D.; Kesque, J.M.; Valda, A.A.; Ilardo, J.C.; Baldo, M.; Erhardt, J.; Debray, M.E.; Somacal, H.R.; Estrada, L.; Sandin, J.C. Suarez; Igarzabal, M.; Huck, H.; Padulo, J.; Minsky, D.M.

    2011-01-01

    The direct use of proton and heavy ion beams for radiotherapy is a well established cancer treatment modality, which is becoming increasingly widespread due to its clear advantages over conventional photon-based treatments. This strategy is suitable when the tumor is spatially well localized. Also the use of neutrons has a long tradition. Here Boron Neutron Capture Therapy (BNCT) stands out, though on a much smaller scale, being a second-generation promising alternative for tumors which are diffuse and infiltrating. On this sector, so far only nuclear reactors have been used as neutron sources. In this paper we describe the current situation worldwide as far as the use of accelerator-based neutron sources for BNCT is concerned (so-called Accelerator-Based (AB)-BNCT). In particular we discuss the present status of an ongoing project to develop a folded Tandem-ElectroStatic-Quadrupole (TESQ) accelerator at the Atomic Energy Commission of Argentina. The project goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the 7 Li(p,n) 7 Be reaction. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams to perform BNCT for deep-seated tumors in less than an hour. (author)

  10. Boron neutron capture therapy for children with malignant brain tumor

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Komatsu, Hisao; Kageji, Teruyoshi; Tsuji, Fumio; Matsumoto, Keizo; Kitamura, Katsuji; Hatanaka, Hiroshi; Minobe, Takashi.

    1993-01-01

    Among the 131 cases with brain tumors treated by boron-neutron capture therapy (BNCT), seventeen were children. Eight supratentorial tumors included five astrocytomas(grade 2-4), two primitive neuroectodermal tumors (PNET) and one rhabdomyosarcoma. Seven pontine tumors included one astrocytoma, one PNET and 5 unverified gliomas. Two cerebellar tumors (PNET and astrocytoma) were also treated. All pontine tumors showed remarkable decrease in size after BNCT. However, most of them showed regrowth of the tumors because the neutrons were insufficient due to the depth. Four cases with cerebral tumor died of remote cell dissemination, although they all responded to BNCT. One of them survived 7 years after repeated BNCTs. An 11 years old girl with a large astrocytoma in the right frontal lobe has lived more than 11 years and is now a draftswoman at a civil engineering company after graduating from a technical college. An 8 years old girl with an astrocytoma in the left occipital lobe has no recurrence of the tumor for 2 years and attends on elementary school without mental and physical problems. Two children (one year old girl and four years old boy) with cerebellar tumors have shown showed an excellent growth after BNCT and had no neurological deficits. Mental and physical development in patients treated by BNCT is usually better than that in patients treated by conventional radiotherapy. (author)

  11. Clinical results of boron neutron capture therapy (BNCT) for glioblastoma

    International Nuclear Information System (INIS)

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

    2011-01-01

    The purpose of this study was to evaluate the clinical outcome of BSH-based intra-operative BNCT (IO-BNCT) and BSH and BPA-based non-operative BNCT (NO-BNCT). We have treated 23 glioblastoma patients with BNCT without any additional chemotherapy since 1998. The median survival time (MST) of BNCT was 19.5 months, and 2-year, 3-year and 5-year survival rates were 26.1%, 17.4% and 5.8%, respectively. This clinical result of BNCT in patients with GBM is superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment. - Highlights: ► In this study, we evaluate the clinical outcome of boron neutron capture therapy (BNCT) for malignant brain tumors. ► We have treated 23 glioblastoma (GBM) patients with BNCT without any additional chemotherapy. ► Clinical results of BNCT in patients with GBM are superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment.

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

    Science.gov (United States)

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

    2008-10-01

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

  13. Boron neutron capture therapy for recurrent head and neck malignancies

    International Nuclear Information System (INIS)

    Kato, Itsuro; Ono, Koji; Ohmae, Masatoshi

    2005-01-01

    Boron neutron capture therapy (BNCT) is a tumor-cell targeted radiotherapy. When 10 B absorbs thermal neutrons, the alpha and 7 Li particles generated by the 10 B (n, α) 7 Li reaction are high linear energy transfer (LET) particles, and carry high kinetic energy (2.34 MeV), and have short ranges (4-9 micron-meters) of approximately one-cell diameter, resulting in a large relative biological effectiveness (RBE) and selective destruction of tumor cells containing 10 B. We have, for the first time in the world, used BNCT to treat 11 patients with recurrent head and neck malignancies (HNM) after a standard primary therapy since 2001. The 11 patients were composed of 6 squamous cell carcinomas, 3 salivary gland tumors and 2 sarcomas. The results of BNCT were as follows. Regression rates (volume %) were complete response (CR): 2 cases, >90%: 5 cases, 73%: 1 case, 54%: 1 case, progressive disease (PD): 1 case, NE (not evaluated): 1 case. The response rate was 82%. Improvement of quality of life (QOL) was recognized, such as disappearance of tumor ulceration and covering with normal skin: relief of severe pain, bleeding, trismus and dyspnea: improvement of performance status (PS) (from 4 to 2) allowing the patients to return to work and elongate his survival period. Survival periods after BNCT were 1-38 months (mean: 8.5 months). The survival rate was 36% (4 cases). There are a few side-effects such as transient mucositis and alopecia less than Grade-2. These results indicate that BNCT represents a new and promising treatment approach even for a huge or far-advanced HNM. (author)

  14. MCNP speed advances for boron neutron capture therapy

    International Nuclear Information System (INIS)

    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

  15. MCNP speed advances for boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Proceedings of workshop on 'boron chemistry and boron neutron capture therapy'

    International Nuclear Information System (INIS)

    Kitaoka, Yoshinori

    1992-09-01

    This volume contains the proceedings of the 4th Workshop on 'the Boron Chemistry and Boron Neutron Capture Therapy' held on February 24 in 1992. First, clinical experiences of BNCT in the Kyoto University Research Reactor in 1992 were briefly reported. Then, the killing effects of boron cluster-containing nucleic acid precursors on tumor cells were shown (Chap. 2). The various trials of the optical resolution of B-p-boronophenylalanine for neutron capture therapy were made (Chap. 3). The borate-dextran gel complexes were investigated by the nuclear magnetic resonance spectroscopy. The stability constants of borate complexes were listed, and are useful in the solution chemistry of boron compounds (Chap. 4). The interactions between boron compounds and biological materials were studied by the paper electrophoresis which had been developed by us (Chap. 5). Molecular design of boron-10 carriers and their organic synthesis were reported (Chap. 6). Carborane-containing aziridine boron carriers which were directed to the DNA alkylation were synthesized and their cancer cell killing efficacies were tested (Chap. 7). The solution chemistry of deuterium oxide which is a good neutron moderator was reported, relating to the BNCT (Chap. 8). (author)

  17. A large animal model for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Gavin, P.R.; Kraft, S.L.; DeHaan, C.E.; Moore, M.P.; Griebenow, M.L.

    1992-01-01

    An epithermal neutron beam is needed to treat relatively deep seated tumors. The scattering characteristics of neutrons in this energy range dictate that in vivo experiments be conducted in a large animal to prevent unacceptable total body irradiation. The canine species has proven an excellent model to evaluate the various problems of boron neutron capture utilizing an epithermal neutron beam. This paper discusses three major components of the authors study: (1) the pharmacokinetics of borocaptate sodium (NA 2 B 12 H 11 SH or BSH) in dogs with spontaneously occurring brain tumors, (2) the radiation tolerance of normal tissues in the dog using an epithermal beam alone and in combination with borocaptate sodium, and (3) initial treatment of dogs with spontaneously occurring brain tumors utilizing borocaptate sodium and an epithermal neutron beam

  18. Boron nanoparticles inhibit turnour growth by boron neutron capture therapy in the murine B16-OVA model

    DEFF Research Database (Denmark)

    Petersen, Mikkel Steen; Petersen, Charlotte Christie; Agger, Ralf

    2008-01-01

    Background: Boron neutron capture therapy usually relies on soluble, rather than particulate, boron compounds. This study evaluated the use of a novel boron nanoparticle for boron neutron capture therapy. Materials and Methods: Two hundred and fifty thousand B16-OVA tumour cells, pre......-incubated with boron nanoparticles for 12 hours, were injected subcutaneously into C57BL16J mice. The tumour sites were exposed to different doses of neutron radiation one, four, or eight days after tumour cell inoculation. Results: When the tumour site was irradiated with thermal neutrons one day after injection......, tumour growth was delayed and the treated mice survived longer than untreated controls (median survival time 20 days (N=8) compared with 10 days (N=7) for untreated mice). Conclusion: Boron nanoparticles significantly delay the growth of an aggressive B16-OVA tumour in vivo by boron neutron capture...

  19. Biocompatibility of functionalized boron phosphate (BPO4) nanoparticles for boron neutron capture therapy (BNCT) application.

    Science.gov (United States)

    Achilli, Cesare; Grandi, Stefania; Ciana, Annarita; Guidetti, Gianni F; Malara, Alessandro; Abbonante, Vittorio; Cansolino, Laura; Tomasi, Corrado; Balduini, Alessandra; Fagnoni, Maurizio; Merli, Daniele; Mustarelli, Piercarlo; Canobbio, Ilaria; Balduini, Cesare; Minetti, Giampaolo

    2014-04-01

    Boron neutron capture therapy (BNCT) is a radiotherapy treatment based on the accumulation in the tumor of a (10)B-containing drug and subsequent irradiation with low energy neutrons, which bring about the decay of (10)B to (7)Li and an α particle, causing the death of the neoplastic cell. The effectiveness of BNCT is limited by the low delivery and accumulation of the used boron-containing compounds. Here we report the development and the characterization of BPO4 nanoparticles (NPs) as a novel possible alternative drug for BNCT. An extensive analysis of BPO4 NP biocompatibility was performed using both mature blood cells (erythrocytes, neutrophils and platelets) and a model of hematopoietic progenitor cells. A time- and concentration-dependent cytotoxicity study was performed on neoplastic coloncarcinoma and osteosarcoma cell lines. BPO4 functionalization with folic acid, introduced to improve the uptake by tumor cells, appeared to effectively limit the unwanted effects of NPs on the analyzed blood components. Boron neutron capture therapy (BNCT) is a radiotherapy treatment modality based on the accumulation of a (10)B-containing drug and subsequent irradiation with low energy neutrons, inducing the decay of (10)B to (7)Li and an α particle, causing neoplastic cell death. This team of authors reports on a folic acid functionalized BPO4 nanoparticle with improved characteristics compared with conventional BNCT approaches, as demonstrated in tumor cell lines, and hopefully to be followed by translational human studies. © 2014.

  20. Neutron capture therapies

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Neutron capture therapies

    Science.gov (United States)

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

    1999-01-01

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

  2. Proceedings of workshop on 'boron chemistry and boron neutron capture therapy'

    International Nuclear Information System (INIS)

    Kitaoka, Yoshinori

    1993-09-01

    This volume contains the proceedings of the 5th Workshop on 'the Boron Chemistry and Boron Neutron Capture Therapy' held on February 22 in 1993. The solubility of the boron carrier play an important role in the BNCT. New water-soluble p-boronophenylalanine derivatives are synthesized and their biological activities are investigated (Chap. 2 and 3). Some chemical problems on the BNCT were discussed, and the complex formation reaction of hydroxylboryl compounds were studied by the paper electrophoresis (Chap. 4). The results of the medical investigation on the BNCT using BSH compounds are shown in Chap. 5. Syntheses of o- and m-boronophenylalanine were done and their optical resolution was tried (Chap. 6). The complex formation reaction of p-boronophenylalanine (BPA) with L-DOPA and the oxidation reaction of the analogs are found in Chap. 7. The pka of BPA were determined by the isotachophoresis (Chap. 8). The chemical nature of dihydroxyboryl compounds were investigated by an infrared spectroscopy and electrophoresis (Chap. 9). New synthetic methods of BPA and p-boronophenylserine using ester of isocyanoacetic acid are described in Chap. 10. The induction of chromosomal aberations by neutron capture reaction are discussed from a point of the biological view. The a of the presented papers are indexed individually. (J.P.N.)

  3. Boron neutron capture therapy (BNCT) using fast neutrons: Effects in two human tumor cell lines

    International Nuclear Information System (INIS)

    Sauerwein, W.; Ziegler, W.; Szypniewski, H.; Streffer, C.

    1990-01-01

    The results demonstrate that the effect of fast neutrons on cell survival in cell culture can be enhanced by boron neutron capture reaction. Even with lower enhancement ratios, the concept of NCT assisted fast neutron therapy may successfully be applied for tumor treatment with the Essen cyclotron. (orig.)

  4. Possible alternation of the blood-brain barrier by boron-neutron capture therapy

    International Nuclear Information System (INIS)

    Hatanaka, H.; Moritani, M.; Camillo, M.

    1991-01-01

    In the course of re-assessment of boron-neutron capture therapy (BNCT) for malignant brain tumors, fractionation of neutron irradiation has been proposed. The authors have used BNCT with a single fraction technique during the past 21 years and now decided to study some effects of fractionation. Twenty-two healthy mouse brains were irradiated with thermal neutrons after boron-10 injection (mercaptoundecahydrododecaborate). A second dose of boron-10 was administered and its uptake in the boron-neutron-capture-irradiated brains was determined. A tendency towards increased boron uptake in the moderately BNCT-treated brains was noticed, which may result in increased brain damage if fractionated neutron irradiation is used. (orig.)

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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. - Highlights: • Herein, we have synthesized boron-modified diblock copolymer. • Bpin-PLA-PEOz, which will be served as new boron containing vehicle for transporting the boron drug. • This boron containing Bpin-PLA-PEOz micelle was low toxicity can be applied to drug delivery

  6. Commercial Clinical Application of Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    1999-01-01

    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 2 B 10 H 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, C.F.; Lin, S.Y. [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Peir, J.J. [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China); Liao, J.W. [Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taiwan (China); Lin, Y.C. [Department of Veterinary Medicine, National Chung Hsing University, Taiwan (China); Chou, F.I., E-mail: fichou@mx.nthu.edu.tw [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China)] [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China)

    2011-12-15

    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 {mu}g {sup 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 {sup 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.

  8. New approaches to novel boronated porphyrins for neutron capture therapy

    International Nuclear Information System (INIS)

    Kahl, S.B.

    1986-01-01

    The use of boon compounds in the treatment of human cancer is based on the unique ability of nonradioactive 10 B nuclei to absorb thermal neutrons. The prompt nuclear reactions, which occur in neutron absorption, deliver a dose of nearly 2.8 MeV only in the vicinity of boron-containing cells, since the nuclear garments produced (alpha particles and recoil lithium atoms) travel only 10 to 15 μm. The practical, clinical use of this technique to date has been limited by the authors inability to target boron-containing compounds specifically to tumor cells in amounts sufficient for therapy and in a chemical form that has an acceptable level of toxicity. Porphyrins are one important and large class of compounds that are known to accumulate in practically all tumor systems yet examined. Such site-specific accumulation is not known to be based on any currently identifiable selective transport mechanism and yet is observed for both natural and synthetic porphyrins. Tetraphenylporphine sulfonate (TPPS) has been shown by Fairchild et al. to be an ideal model compound for assessing porphyrin uptake, and suitably boronated tetraphenyl porphine might be expected to behave similarly. This report describes the synthesis, properties, and preliminary biodistribution of such compounds

  9. Feasibility of boron neutron capture therapy for malignant spinal tumors

    International Nuclear Information System (INIS)

    Nakai, Kei; Kumada, Hiroaki; Yamamoto, Tetsuya; Tsurubuchi, Takao; Zaboronok, Alexander; Matsumura, Akira

    2009-01-01

    Treatment of malignant spinal cord tumors is currently ineffective. The characteristics of the spine are its seriality, small volume, and vulnerability: severe QOL impairment can be brought about by small neuronal damage. The present study aimed to investigate the feasibility of BNCT as a tumor-selective charged particle therapy for spinal cord tumors from the viewpoint of protecting the normal spine. A previous report suggested the tolerance dose of the spinal cord was 13.8 Gy-Eq for radiation myelopathy; a dose as high as 11 Gy-Eq demonstrated no spinal cord damage in an experimental animal model. We calculated the tumor dose and the normal spinal cord dose on a virtual model of a spinal cord tumor patient with a JAEA computational dosimetry system (JCDS) treatment planning system. The present study made use of boronophenylalanine (BPA). In these calculations, conditions were set as follows: tumor/normal (T/N) ratio of 3.5, blood boron concentration of 12 ppm, tumor boron concentration of 42 ppm, and relative biological effectiveness (RBE) values for tumor and normal spinal cord of 3.8 and 1.35, respectively. We examined how to optimize neutron irradiation by changing the beam direction and number. In our theoretical example, simple opposed two-field irradiation achieved 28.0 Gy-Eq as a minimum tumor dose and 7.3 Gy-Eq as a maximum normal spinal dose. The BNCT for the spinal cord tumor was therefore feasible when a sufficient T/N ratio could be achieved. The use of F-BPA PET imaging for spinal tumor patients is supported by this study.

  10. Development of a Boron Neutron Capture Enhanced Fast Neutron Therapy Beam

    Energy Technology Data Exchange (ETDEWEB)

    Sweezy, Jeremy Ed [Georgia Tech

    2002-01-01

    The combination of fast neutron therapy and boron neutron capture therapy is currently under investigation at several fast neutron therapy centers worldwide. This treatment method, termed boron neutron capture enhanced fast neutron therapy (BNCEFNT) utilizes a boron containing drug to selectively increase the dose to the target tumor. BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiforme. A neutron therapy beam for boron neutron capture enhanced fast neutron therapy has been developed for the existing Fermilab Neutron Therapy Facility. This beam produces a significant dose enhancement due to the the boron neutron capture reaction. The beam was developed by designing a filter and collimator system using the Monte Carlo radiation transport code, MCNPX. The MCNPX code was benchmarked against depth-dose measurements of the standard treatment beam. The new BNCEFNT beam is filtered with 18.3-cm of low carbon steel and is collimated with steel. Measurements of the dose enhancement of the new BNCEFNT beam were performed with paired tissue equivalent ion chambers. One of the ion chambers has boron incorporated in the wall of the chamber to measure the dose due to boron neutron capture. The measured boron dose enhancement of the BNCEFNT beam is (16.3 ± 2.6)% per 100-ppm 10B for a 20-cm diameter beam and (10.0 ± 1.6)% per 100-ppm 10B for a 10-cm diameter beam. The dose rate of the new beam is reduced to 4.4% of the dose rate of the standard treatment beam. xxi A conceptual design that overcomes the reduced dose rate is also presented. This design uses a tungsten collimator placed near the patient, with a 1.5-cm tungsten filter just upstream of the collimator. Using graphite moderation of neutrons around the patient a percent dose enhancement of 15% can be attained with good collimation, for field sizes as small as 5 × 5 cm2 , and without a reduction in dose rate.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  12. Synthesis and biological evaluation of boronated polyglycerol dendrimers as potential agent for neutron capture therapy

    International Nuclear Information System (INIS)

    Silva, Gerald S.; Camillo, Maria A.P.; Higa, Olga Z.; Pugliesi, Reynaldo; Fermamdes, Edson G.R.; Queiroz, Alvaro A.A. de

    2005-01-01

    In this work, the polyglycerol dendrimer (PGLD) generation 5 was used to obtain a boronated macromolecule for boron neutron capture therapy. The PGLD dendrimer was synthesized by the ring opening polymerization of deprotonated glycidol using polyglycerol as core functionality in a step-growth processes denominated divergent synthesis. The PGLD dendritic structure was confirmed by gel permeation chromatography, nuclear magnetic resonance ( 1 H-NMR, 13 C-NMR) and matrix assisted laser desorption/ionization techniques. The synthesized dendrimer presented low dispersion in molecular weights (M w /M n = 1.05) and a degree of branching of 0.82, which characterize the polymer dendritic structure. Quantitative neutron capture radiography was used to investigate the boron-10 enrichment of the polyglycerol dendrimer. The in vitro cytotoxicity to Chinese hamster ovary cells of 10 B-PGLD dendrimer indicate lower cytotoxicity, suggesting that the macromolecule is a biocompatible material. (author)

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Note: Development of real-time epithermal neutron detector for boron neutron capture therapy.

    Science.gov (United States)

    Tanaka, H; Sakurai, Y; Takata, T; Watanabe, T; Kawabata, S; Suzuki, M; Masunaga, S-I; Taki, K; Akabori, K; Watanabe, K; Ono, K

    2017-05-01

    The real-time detection of epithermal neutrons forms an important aspect of boron neutron capture therapy. In this context, we developed an epithermal neutron detector based on the combination of a small Eu:LiCaAlF 6 scintillator and a quartz fiber in order to fulfill the irradiation-field requirements for boron neutron capture therapy. The irradiation test is performed with the use of a reactor-based neutron source. The thermal and epithermal neutron sensitivities of our epithermal neutron detector are estimated to be 9.52 × 10 -8 ± 1.59 × 10 -8 cm 2 and 1.20 × 10 -6 cm 2 ± 8.96 × 10 -9 cm 2 , respectively. We also subject the developed epithermal neutron detector to actual irradiation fields, and we confirm that the epithermal neutron flux can be measured in realtime.

  15. Physics of epi-thermal boron neutron capture therapy (epi-thermal BNCT).

    Science.gov (United States)

    Seki, Ryoichi; Wakisaka, Yushi; Morimoto, Nami; Takashina, Masaaki; Koizumi, Masahiko; Toki, Hiroshi; Fukuda, Mitsuhiro

    2017-12-01

    The physics of epi-thermal neutrons in the human body is discussed in the effort to clarify the nature of the unique radiologic properties of boron neutron capture therapy (BNCT). This discussion leads to the computational method of Monte Carlo simulation in BNCT. The method is discussed through two examples based on model phantoms. The physics is kept at an introductory level in the discussion in this tutorial review.

  16. Using BPA alone for boron neutron capture therapy of recurrent head and neck malignancies

    International Nuclear Information System (INIS)

    Aihara, Teruhito; Hiratsuka, Junichi; Nishiike, Suetaka; Morita, Norimasa; Uno, Masako; Harada, Tamotsu; Sakurai, Yoshinori; Maruhashi, Akira; Ono, Koji

    2006-01-01

    In recent years, boron neutron capture therapy(BNCT) has been established as a special treatment technique for overcoming the radiation resistance of malignant melanomas and brain tumors. Head and neck malignancies were consequently selected as adaptable cancers. We report the clinical results of treatment with BPA alone utilizing 18 F-BPA·PET and discuss several advantages to the application of BNCT to head and neck malignancies. (author)

  17. Long-survivors of glioblatoma treated with boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

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

    2011-01-01

    The purpose of this study was to compare the radiation dose between long-survivors and non-long-survivors in patients with glioblatoma (GBM) treated with boron neutron capture therapy (BNCT). Among 23 GBM patients treated with BNCT, there were five patients who survived more than three years after diagnosis. The physical and weighted dose of the minimum gross tumor volume (GTV) of long-survivors was much higher than that of non-long survivors with significant statistical differences.

  18. SBNCT plan: A 3-dimensional treatment planning system for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Reinstein, L.E.; Ramsay, E.B.; Gajewski, J.; Ramamoorthy, S.; Meek, A.G.

    1993-01-01

    The need for accurate and comprehensive 3-dimensional treatment planning for boron neutron capture therapy (BNCT) has been debated for the past several years. Although many argue against the need for elaborate and expensive treatment planning programs which mimic conventional radiotherapy planning systems, it is clear that in order to realize significant gains over conventional fractionated radiation therapy, patients must be treated to the edge of normal tissue tolerance. Just how close to this edge is dictated by the uncertainties in dosimetry. Hence the focus of BNCT planning is the determination of dose distribution throughout normal tissue volumes. Although precise geometric manipulation of the epithermal neutron beam is not achievable, the following variables play an important role in BNCT optimization: patient orientation, dose fractionation, number of fields, megawatt-minutes per fraction, use of surface bolus, and use of collimation. Other variables which are not as easily adjustable and would not, therefore, be part of treatment planning optimization, include external patient contour, internal patient heterogeneities, boron compound distributions, and RBE's. The boron neutron capture therapy planning system developed at SUNY Stony Brook (SBNCT-Plan) was designed as an interactive graphic tool to assist the radiation oncologist in generating the optimum plan for a neutron capture treatment

  19. Radiologic findings in patients treated with boron neutron capture therapy for glioblastoma multiforme within EORTC trial 11961

    NARCIS (Netherlands)

    Vos, Maaike J.; Turowski, Bernd; Zanella, Friedhelm E.; Paquis, Philippe; Siefert, Axel; Hideghéty, Katalin; Haselsberger, Klaus; Grochulla, Frank; Postma, Tjeerd J.; Wittig, Andrea; Heimans, Jan J.; Slotman, Ben J.; Vandertop, W. Peter; Sauerwein, Wolfgang

    2005-01-01

    PURPOSE: To assess the occurrence and development of cerebral radiologic changes (cerebral atrophy and white matter lesions) in patients treated with boron neutron capture therapy (BNCT) for primary supratentorial glioblastoma multiforme within the European Organization for Research and Treatment of

  20. Nuclear Physics meets Medicine and Biology: Boron Neutron Capture Therapy

    CERN Document Server

    F. Ballarini, F; S. Bortolussi, S; P. Bruschi, P; A.M. Clerici, A M; A. De Bari, A; P. Dionigi, P; C. Ferrari, C; M.A. Gadan, M A; N. Protti, N; S. Stella, S; C. Zonta, C; A. Zonta, A; S. Altieri, S

    2010-01-01

    BNCT is a tumour treatment based on thermal-neutron irradiation of tissues enriched with 10B, which according to the 10B(n, )7Li reaction produces particles with high Linear Energy Transfer and short range. Since this treatment can deliver a therapeutic tumour dose sparing normal tissues, BNCT represents an alternative for diffuse tumours and metastases, which show poor response to surgery and photontherapy. In 2001 and 2003, in Pavia BNCT was applied to an isolated liver, which was infused with boron, explanted, irradiated and re-implanted. A new project was then initiated for lung tumours, developing a protocol for Boron concentration measurements and performing organ-dose Monte Carlo calculations; in parallel, radiobiology studies are ongoing to characterize the BNCT effects down to cellular level. After a brief introduction, herein we will present the main activities ongoing in Pavia including the radiobiological ones, which are under investigation not only experimentally but also theoretically, basing on...

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

    International Nuclear Information System (INIS)

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

    1995-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Joel, D.D.; Bergland, R.; Capala, J. [and others

    1995-12-31

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

  3. Macromolecular structures for boron neutron-capture therapy

    International Nuclear Information System (INIS)

    Kne, R.R.; Hawthorne, M.F.

    1995-01-01

    A general synthetic method has been developed for the rapid and efficient production of a variety of boron-rich macromolecules suitable for conjugation with or inclusion in receptor-mediated delivery systems as well as other delivery systems. Preparation techniques have been developed to yield precisely ordered oligophosphates which are soluble, hydrophilic, may be homogeneous, and may be prepared with a variety of functional groups. (author)

  4. Medical aspects of boron-slow neutron capture therapy

    International Nuclear Information System (INIS)

    Sweet, W.H.

    1986-01-01

    Earlier radiations of patients with cerebral tumors disclosed the need: (1) to find a carrier of the boron compound which would leave the blood and concentrate in the tumor, (2) to use a more penetrating neutron beam, and (3) to develop a much faster method for assaying boron in blood and tissue. To some extent number1 has been accomplished in the form of Na 2 B 12 H 11 SH, number2 has yet to be achieved, and number3 has been solved by the measurement of the 478-keV gamma ray when the 10 B atom disintegrates following its capture of a slow neutron. The hitherto unreported data in this paper describe through the courtesy of Professor Hiroshi Hatanaka his studies on the pharmacokinetics and quality control of Na 2 B 12 H 11 SH based on 96 boron infusions in 86 patients. Simultaneous blood and tumor data are plotted here for 30 patients with glioblastomas (Grade III-IV gliomas), illustrating remarkable variability. Detailed autopsy findings on 18 patients with BNCT showed radiation injury in only 1. Clinical results in 12 of the most favorably situated glioblastomas reveal that 5 are still alive with a 5-year survival rate of 58% and the excellent Karnofsky performance rating of 87%. For the first time evidence is presented that slow-growing astrocytomas may benefit from BNCT. 10 references, 8 figures, 5 tables

  5. In vitro and in vivo studies in boron neutron capture therapy of malignant melanoma

    International Nuclear Information System (INIS)

    Allen, B.J.

    1982-01-01

    A multidisciplinary research project in boron neutron capture therapy of malignant melanoma is under consideration by the Australian Atomic Energy Commission. This paper reviews the biochemistry of melanoma and the properties of some melanoma-affined radiopharmaceuticals and their boron analogues. Human cell lines are being used for in vitro tests of uptake and incorporation of some of these compounds, and selected lines will then be implanted in nude mice for in vivo distribution studies. The fidelity of human melanoma xenografts in nude mice has been well studied, and results are reviewed in this paper. Boron concentration will be measured directly by plasma arc emission spectroscopy or liquid scintillation counting with 14 C-labelled boron analogues. Track-etch techniques will be used for the microscopic determination of boron in tumor sections. Neutron irradiation and radiobiology experiments are outlined

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

    Science.gov (United States)

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

    2015-12-01

    The selective delivery of (10)B into the tumor tissue remains to be further improved for successful and reliable Boron Neutron Capture Therapy applications. Magnetic Drug Targeting using intraarterially administered superparamagnetic nanoparticles and external magnetic fields already exhibited convincing results in terms of highly efficient and selective drug deposition. Using the same technique for the targeted (10)B delivery is a promising new approach. Here, systematic irradiation experiments of phantom cubes containing different concentrations of boron and nanoparticles as well as varying three-dimensional arrangements have been performed. Copyright © 2015. Published by Elsevier Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhonglu [Georgia Inst. of Technology, Atlanta, GA (United States)

    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

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

    International Nuclear Information System (INIS)

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

    1996-01-01

    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 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/ 10 B reactions ( 10 B(n,α) 7 Li) resulting in the production of localized high LET radiation from alpha and 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Joel, D.D.; Coderre, J.A.; Chanana, A.D. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.

    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.

  10. Monte Carlo calculations on efficiency of boron neutron capture therapy for brain cancer

    International Nuclear Information System (INIS)

    Awadalla, Galaleldin Mohamed Suliman

    2015-11-01

    The search for ways to treat cancer has led to many different treatments, including surgery, chemotherapy, and radiation therapy. Among these treatments, boron neutron capture therapy (BNCT) has shown promising results. BNCT is a radiotherapy treatment modality that has been proposed to treat brain cancer. In this technique, cancerous cells are being injected with 1 0B and irradiated by thermal neutrons to increase the probability of 1 0B (n, a)7 L i reaction to occur. This reaction can potentially deliver a high radiation dose sufficient to kill cancer cells by concentrating boron in them. The short rang of 1 0B (n, a) 7 L i reaction limits the damage to only cancerous cells without affecting healthy tissues. The effectiveness and safety of radiotherapy are dependent on the radiation dose delivered to the tumor and healthy tissues. In this thesis, after reviewing the basics and working principles of boron neutron capture therapy (BNCT), monte Carlo simulations were carried out to model a thermal neutron source suitable for BNCT and to examine the performance of proposed model when used to irradiate a sample of boron containing both 1 0B and 1 1B isotopes. MCNP5 code was used to examine the modeled neutron source through different shielding materials. The results were presented, analyzed and discussed at the end of the work. (author)

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Neutron therapy coupling brachytherapy and boron neutron capture therapy (BNCT) techniques

    International Nuclear Information System (INIS)

    Chaves, Iara Ferreira.

    1994-12-01

    In the present dissertation, neutron radiation techniques applied into organs of the human body are investigated as oncologic radiation therapy. The proposal treatment consists on connecting two distinct techniques: Boron Neutron Capture Therapy (BNCT) and irradiation by discrete sources of neutrons, through the brachytherapy conception. Biological and radio-dosimetrical aspects of the two techniques are considered. Nuclear aspects are discussed, presenting the nuclear reactions occurred in tumoral region, and describing the forms of evaluating the dose curves. Methods for estimating radiation transmission are reviewed through the solution of the neutron transport equation, Monte Carlo methodology, and simplified analytical calculation based on diffusion equation and numerical integration. The last is computational developed and presented as a quickly way to neutron transport evaluation in homogeneous medium. The computational evaluation of the doses for distinct hypothetical situations is presented, applying the coupled techniques BNTC and brachytherapy as an possible oncologic treatment. (author). 78 refs., 61 figs., 21 tabs

  13. Biological models in vivo for boron neutronic capture studies as tumors therapy

    International Nuclear Information System (INIS)

    Kreimann, Erica L.; Dagrosa, Maria A.; Schwint, Amanda E.; Itoiz, Maria E.; Pisarev, Mario A.; Farias, Silvia S.; Garavaglia, Ricardo N.; Batistoni, Daniel A.

    1999-01-01

    The use of experimental models for Boron Neutronic Capture studies as Tumors Therapy have as two main objectives: 1) To contribute to the basic knowledge of the biological mechanisms involved to increase the method therapeutical advantage, and 2) To explore the possible application of this therapeutic method to other pathologies. In this frame it was studied the carcinogenesis model of hamster cheek pouch, a type of human buccal cancer. Biodistribution studies of boron compound were performed in tumor, blood and in different precancerous and normal tissues as well as BNCT studies. Results validated this method for BNCT studies and show the capacity of the oral mucosa tumors of selectively concentrate the boron compound, showing a deleterious clear effect on the tumor after 24 hours with BNCT treatment. (author)

  14. A shielding design for an accelerator-based neutron source for boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hawk, A.E.; Blue, T.E. E-mail: blue.1@osu.edu; Woollard, J.E

    2004-11-01

    Research in boron neutron capture therapy (BNCT) at The Ohio State University Nuclear Engineering Department has been primarily focused on delivering a high quality neutron field for use in BNCT using an accelerator-based neutron source (ABNS). An ABNS for BNCT is composed of a proton accelerator, a high-energy beam transport system, a {sup 7}Li target, a target heat removal system (HRS), a moderator assembly, and a treatment room. The intent of this paper is to demonstrate the advantages of a shielded moderator assembly design, in terms of material requirements necessary to adequately protect radiation personnel located outside a treatment room for BNCT, over an unshielded moderator assembly design.

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

    OpenAIRE

    Wang, Peng; Zhen, Haining; Jiang, Xinbiao; Zhang, Wei; Cheng, Xin; Guo, Geng; Mao, Xinggang; Zhang, Xiang

    2010-01-01

    Abstract 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 Un...

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. The Boron Neutron Capture Therapy (BNCT) Project at the TRIGA Reactor in Mainz, Germany

    DEFF Research Database (Denmark)

    Hampel, G.; Grunewald, C.; Schütz, C.

    2011-01-01

    The thermal column of the TRIGA reactor in Mainz is being used very effectively for medical and biological applications. The BNCT (boron neutron capture therapy) project at the University of Mainz is focussed on the treatment of liver tumours, similar to the work performed at Pavia (Italy) a few...... have also been initiated to investigate radiobiological effects of radiation generated during BNCT. For both experiments and treatment, a reliable dosimetry system is necessary. From work elsewhere, the use of alanine detectors appear to be an appropriate dosimetry technique....

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

    Science.gov (United States)

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

    2014-10-01

    Monte Carlo simulations were performed to evaluate dose for possible treatment of cancers by boron neutron capture therapy (BNCT). The computational model of male Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the lung. Calculations have been performed by means of the MCNP5/X code. In this simulation, two opposite neutron beams were considered, in order to obtain uniform neutron flux distribution inside the lung. The obtained results indicate that the lung cancer could be treated by BNCT under the assumptions of calculations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. For boron neutron capture therapy,synthesizing boron-polymer compounds and testing in laboratory conditions

    International Nuclear Information System (INIS)

    2011-01-01

    The aim of this project is to establish a focus point at Turkish Atomic Energy Authority (TAEA) in the field of Boron Neutron Capture Therapy which is a binary radiotherapy method for brain tumours. Moreover in the scope of the project, a new alternative of 1 0B-carrier compounds will be synthesized, the neutron source will be determined and the infrastructure to start the clinical trials of BNCT in our country will be established. BNCT is a binary radiotherapy method and the successful of this method is depend on the synthesized boron compounds which have the selective targeting property with tumour cells and neutron optimization. The water-soluble polymer based boron compounds having biochemical and physiological properties will be synthesized and cell culture experiment will be done. In addition, after the neutron source is set up in our country, the infrastructure studies will be started in order to start the clinical trials of BNCT. In this project, there are three different groups as boron compounds, neutron physics and medical group. Neutron physics group is starting the calculations of neutron beam parameters using in BNCT application. But, medical group has no active studies yet. Boron compounds group has been carried out two different experimental studies. In the first experimental study, functional groups have been bound to boron containing polymers to enhance the selectively targeting property and characterized by various analysis methods. Later, cell culture experiment will be done. The first study has been carried out with Hacettepe University. Up to present, completed studies are listed as: -Maleic anhydride oligomer was synthesized and then 2-aminoethyl diphenyl borate (2-AEPB) and monomethoxy poly(ethylene glycol) (PEG) was bound to this oligomer, respectively. Thus, [MAH] n -g 1 -2-AEPB-g 2 -PEG was synthesized. -2-AEPB compound were bound to poly(acrylic acid) polymer at different three mole ratio.Then, the selected Poli(Ac)-g 1 -2-AEPB polymer

  20. An Assessment of the Potential Use of BNNTs for Boron Neutron Capture Therapy.

    Science.gov (United States)

    Ferreira, Tiago H; Miranda, Marcelo C; Rocha, Zildete; Leal, Alexandre S; Gomes, Dawidson A; Sousa, Edesia M B

    2017-04-12

    Currently, nanostructured compounds have been standing out for their optical, mechanical, and chemical features and for the possibilities of manipulation and regulation of complex biological processes. One of these compounds is boron nitride nanotubes (BNNTs), which are a nanostructured material analog to carbon nanotubes, but formed of nitrogen and boron atoms. BNNTs present high thermal stability along with high chemical inertia. Among biological applications, its biocompatibility, cellular uptake, and functionalization potential can be highlighted, in addition to its eased utilization due to its nanometric size and tumor cell internalization. When it comes to new forms of therapy, we can draw attention to boron neutron capture therapy (BNCT), an experimental radiotherapy characterized by a boron-10 isotope carrier inside the target and a thermal neutron beam focused on it. The activation of the boron-10 atom by a neutron generates a lithium atom, a gamma ray, and an alpha particle, which can be used to destroy tumor tissues. The aim of this work was to use BNNTs as a boron-10 carrier for BNCT and to demonstrate its potential. The nanomaterial was characterized through XRD, FTIR, and SEM. The WST-8 assay was performed to confirm the cell viability of BNNTs. The cells treated with BNNTs were irradiated with the neutron beam of a Triga reactor, and the apoptosis caused by the activation of the BNNTs was measured with a calcein AM/propidium iodide test. The results demonstrate that this nanomaterial is a promising candidate for cancer therapy through BNCT.

  1. Analytical dosimetry for spontaneous tumor dogs receiving boron neutron capture therapy

    International Nuclear Information System (INIS)

    Wheeler, F.J.; Atkinson, C.A.; Gavin, P.R.

    1992-01-01

    The dog irradiation project of the Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program is administered by Washington State University (WSU) with analytical and physical dosimetry provided by the Idaho National Engineering Laboratory (INEL). One subtask of this project includes BNCT safety studies for dogs with spontaneously-occurring brain tumors. The boron compound (Na 2 B 12 H 11 SH or BSH) was administered and single irradiations performed using the epithermal-neutron beam at the Brookhaven Medical Research Reactor (BMRR). The main goal of the study was not to provide therapy, but to determine tumorcidal effect while administering a subtolerance dose to healthy tissue. Irradiation times were based on delivery of 19 Gy peak physical dose to the blood

  2. Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Haapaniemi, Aaro, E-mail: aaro.haapaniemi@hus.fi [Department of Otorhinolaryngology–Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Kankaanranta, Leena [Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Saat, Riste [Department of Radiology, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Koivunoro, Hanna; Saarilahti, Kauko [Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Mäkitie, Antti; Atula, Timo [Department of Otorhinolaryngology–Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Joensuu, Heikki [Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki (Finland)

    2016-05-01

    Purpose: To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer. Methods and Materials: Six patients with locally recurrent squamous cell laryngeal carcinoma and 3 patients with persistent laryngeal cancer after prior treatment were treated with BNCT at the FiR1 facility (Espoo, Finland) in 2006 to 2012. The patients had received prior radiation therapy with or without concomitant chemotherapy to a cumulative median dose of 66 Gy. The median tumor diameter was 2.9 cm (range, 1.4-10.9 cm) before BNCT. Boron neutron capture therapy was offered on a compassionate basis to patients who either refused laryngectomy (n=7) or had an inoperable tumor (n=2). Boronophenylalanine-fructose (400 mg/kg) was used as the boron carrier and was infused over 2 hours intravenously before neutron irradiation. Results: Six patients received BNCT once and 3 twice. The estimated average gross tumor volume dose ranged from 22 to 38 Gy (W) (mean; 29 Gy [W]). Six of the 8 evaluable patients responded to BNCT; 2 achieved complete and 4 partial response. One patient died early and was not evaluable for response. Most common side effects were stomatitis, fatigue, and oral pain. No life-threatening or grade 4 toxicity was observed. The median time to progression within the target volume was 6.6 months, and the median overall survival time 13.3 months after BNCT. One patient with complete response is alive and disease-free with a functioning larynx 60 months after BNCT. Conclusions: Boron neutron capture therapy given after prior external beam radiation therapy is well tolerated. Most patients responded to BNCT, but long-term survival with larynx preservation was infrequent owing to cancer progression. Selected patients with recurrent laryngeal cancer may benefit from BNCT.

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

    Directory of Open Access Journals (Sweden)

    Schaffran T

    2014-07-01

    Full Text Available Tanja Schaffran,1 Nan Jiang,1 Markus Bergmann,2,3 Ekkehard Küstermann,4 Regine Süss,5 Rolf Schubert,5 Franz M Wagner,6 Doaa Awad,7 Detlef Gabel1,2,8 1Department of Chemistry, University of Bremen, 2Institute of Neuropathology, Klinikum Bremen-Mitte; 3Cooperative Center Medicine, University of Bremen, 4“In-vivo-MR” AG, FB2, University of Bremen, Bremen, 5Pharmaceutical Technology, University of Freiburg, Freiburg im Breisgau, 6Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM II, Technische Unversitaet Muenchen, Garching, Germany; 7Department of Biochemistry, Alexandria University, Alexandria, Egypt; 8School of Engineering and Science, Jacobs University Bremen, Bremen, Germany Abstract: The potential of boron-containing lipids with three different structures, which were intended for use in boron neutron capture therapy, was investigated. All three types of boron lipids contained the anionic dodecaborate cluster as the headgroup. Their effects on two different tumor models in mice following intravenous injection were tested; for this, liposomes with boron lipid, distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing a polyethylene glycol lipid for steric protection, were administered intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell carcinoma and BALB/c mice for CT26/WT colon carcinoma. With the exception of one lipid (B-THF-14, the lipids were well tolerated, and no other animal was lost due to systemic toxicity. The lipid which led to death was not found to be much more toxic in cell culture than the other boron lipids. All of the lipids that were well tolerated showed hemorrhage in both tumor models within a few hours after administration. The hemorrhage could be seen by in vivo magnetic resonance and histology, and was found to occur within a few hours. The degree of hemorrhage depended on the amount of boron administered and on the tumor model. The observed unwanted effect of the lipids

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

    Science.gov (United States)

    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.

  5. Clinical treatment planning for subjects undergoing boron neutron capture therapy at Harvard-MIT

    International Nuclear Information System (INIS)

    Zamenhof, R.G.; Palmer, M.R.; Buse, P.M.

    2001-01-01

    Treatment planning is a crucial component of the Harvard-MIT boron neutron capture therapy (BNCT) clinical trials. Treatment planning can be divided into five stages: (1) pre-planning, based on CT and MRI scans obtained when the subject arrives at the hospital and on assumed boron-10 distribution parameters; (2) subject set-up, or simulation, in the MITR-II medical therapy room to determine the boundary conditions for possible set-up configurations; (3) re-planning, following the subject simulation; (4) final localization of the subject in the medical therapy room for BNCT; and (5) final post facto recalculation of the doses delivered based on firm knowledge of the blood boron-10 concentration profiles and the neutron flux histories from precise online monitoring. The computer-assisted treatment planning is done using a specially written BNCT treatment planning code called MacNCTPLAN. The code uses the Los Alamos National Laboratory's Monte Carlo n-particle radiation transport code MCNPv.4b as the dose calculation engine and advanced anatomical model simulation based on an automatic evaluation of CT scan data. Results are displayed as isodose contours and dose-volume histograms, the latter correlated precisely with corresponding anatomical CT or MRI image planes. Examples of typical treatment planning scenarios will be presented. (author)

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

    DEFF Research Database (Denmark)

    Mortensen, M. W.; Sørensen, P. G.; Björkdahl, O.

    2006-01-01

    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...

  7. Application of drug delivery system to boron neutron capture therapy for cancer.

    Science.gov (United States)

    Yanagië, Hironobu; Ogata, Aya; Sugiyama, Hirotaka; Eriguchi, Masazumi; Takamoto, Shinichi; Takahashi, Hiroyuki

    2008-04-01

    Tumor cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons ((10)B + (1)n --> (7)Li + (4)He (alpha) + 2.31 MeV (93.7 %)/2.79 MeV (6.3 %)). The resulting lithium ions and alphaparticles are high linear energy transfer (LET) particles which give a high biological effect. Their short range in tissue (5 - 9 mum) restricts radiation damage to those cells in which boron atoms are located at the time of neutron irradiation. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer and hepatoma. Sodium mercaptoundecahydro-dodecaborate (Na(2)(10)B(12)H(11)SH: BSH) and borono-phenylalanine ((10)BPA) are currently being used in clinical treatments. These low molecule compounds are easily cleared from cancer cells and blood, so high accumulation and selective delivery of boron compounds into tumor tissues and cancer cells are most important to achieve effective BNCT and to avoid damage to adjacent healthy cells. In order to achieve the selective delivery of boron atoms to cancer cells, a drug delivery system (DDS) is an attractive intelligent technology for targeting and controlled release of drugs. We performed literature searches related to boron delivery systems in vitro and in vivo. We describe several DDS technologies for boron delivery to cancer tissues and cancer cells from the past to current status. We are convinced that it will be possible to use liposomes, monoclonal antibodies and WOW emulsions as boron delivery systems for BNCT clinically in accordance with the preparation of good commercial product (GCP) grade materials.

  8. Application of HVJ envelope system to boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    Nakai, Kei; Kurooka, Masaaki; Kaneda, Yasufumi; Yamamoto, Tetsuya; Matsumura, Akira; Asano, Tomoyuki

    2006-01-01

    Boron Neutron Capture Therapy (BNCT) has been used clinically for the treatment of malignant tumors. Two drugs, p-boronophenylalanine (BPA) and sulfhydral borane (BSH), have been used as boron delivery agents. These drugs seem to be taken up preferentially in solid tumors, but it is uncertain whether therapeutic quantities of boron atoms are taken up by micro-invasive or distant tumor cells. High accumulation and high selective delivery of boron into tumor tissues are the most important requirements to achieve efficient BNCT for malignant tumor. The HVJ envelope (HVJ-E) vector system is a novel fusion-mediated gene delivery system based on inactivated hemagglutinating virus of Japan (HVJ; Sendai virus). Although we developed this vector system for gene transfer, it can also deliver proteins, synthetic oligonucleotides, and drugs. HVJ-liposome, which is liposome fused with HVJ-E, has higher boron trapping efficiency than HVJ-E alone. We report the boron delivery into cultured cells with HVJ-liposome systems. The cellular 10 B concentration after 60 min incubation with HVJ-E containing BSH was 24.9 μg/g cell pellet for BHK-21 cells (baby hamster kidney cells) and 19.4 μg/g cell pellet for SCC VII cells (murine squamous cell carcinoma). These concentrations are higher than that of 60 min incubated cells with BSH containing (100μg 10 B/ml) medium. These results indicate the HVJ-E fused with tumor cell membrane and rapidly delivered boron agents, and that the HVJ-E-mediated delivery system could be applicable to BNCT. Plans are underway to begin neutron radiation experiments in vivo and in vitro. (author)

  9. The Idaho Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program overview

    International Nuclear Information System (INIS)

    Dorn, R.V. III; Griebenow, M.L.; Ackermann, A.L.; Miller, L.G.; Miller, D.L.; Wheeler, F.J.; Bradshaw, K.M.; Wessol, D.E.; Harker, Y.D.; Nigg, D.W.; Randolph, P.D.; Bauer, W.F.; Gavin, P.R.; Richards, T.L.

    1992-01-01

    The Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program has been funded since 1988 to evaluate brain tumor treatment using Na 2 B 12 H 11 SH (borocaptate sodium or BSH) and epithermal neutrons. The PBF/BNCT Program pursues this goal as a comprehensive, multidisciplinary, multiorganizational endeavor applying modern program management techniques. The initial focus was to: (1) establish a representative large animal model and (2) develop the generic analytical and measurement capabilities require to control treatment repeatability and determine critical treatment parameters independent of tumor type and body location. This paper will identify the PBF/BNCT Program elements and summarize the status of some of the developed capabilities

  10. Lattice design of a FFAG accelerator for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Wang Kun; Song Mingtao; Zhang Jinquan; Shenglina

    2014-01-01

    A compact FFAG accelerator for Boron Neutron Capture Therapy (BNCT) has been designed. Firstly, a linear simplified magnet model has been applied to calculate the basic parameters of FFAG accelerator; Then the WINAGILE program is used to design and optimize the lattice, as well as to obtain the critical parameters such as the Beta functions, the dispersion functions, the envelopes and the tunes; Also, the MAD program is used to check the design scheme; Finally, the ZGOUBI program is used to simulate the particles movement in the nonlinear magnetic field. The super period of the FFAG accelerator is 6. The energy is 11 MeV and the eld index k is 1.9. The structure is compact with the circumference of 11.1795 m. The results show that this optimized design has achieved the proposal object. (authors)

  11. Optimal Neutron Source and Beam Shaping Assembly for Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

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

    2003-01-01

    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

  12. Optimal Neutron Source and Beam Shaping Assembly for Boron Neutron Capture Therapy

    CERN Document Server

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

    2003-01-01

    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.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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 5 Gy-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. - Highlights: • This article is written about the dose estimation for internal organs in body-trunk BNCT. • The dose estimations were performed for several internal organs in body-trunk BNCTs for several body tumors, carried out at Kyoto University Research Reactor Institute

  14. Study on high speed lithium jet for neutron source of boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    Takahashi, Minoru; Kobayashi, Tooru; Zhang, Mingguang; Mak, Michael; Stefanica, Jiri; Dostal, Vaclav; Zhao Wei

    2012-01-01

    The feasibility study of a liquid lithium type proton beam target was performed for the neutron source of the boron neutron capture therapy (BNCT). As the candidates of the liquid lithium target, a thin sheet jet and a thin film flow on a concave wall were chosen, and a lithium flow experiment was conducted to investigate the hydrodynamic stability of the targets. The surfaces of the jets and film flows with a thickness of 0.5 mm and a width of 50 mm were observed by means of photography. It has been found that a stable sheet jet and a stable film flow on a concave wall can be formed up to certain velocities by using a straight nozzle and a curved nozzle with the concave wall, respectively. (author)

  15. Progress in study of a medical reactor for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Sasaki, Makoto; Hirota, Jitsuya; Tamao, Shigeo; Kanda, Keiji; Mishima, Yutaka.

    1993-01-01

    A design study of a medical reactor for Boron Neutron Capture Therapy has made progress. Main specifications of the reactor are as follows; thermal power of 2 MW, water cooling by natural convection, semitight core of hexagonal lattice, UO 2 fuel rod of 9.5 mm diameter and no refueling in the reactor-life. Three horizontal and one vertical neutron beam holes are to be provided for simultaneous treatments by thermal and epithermal neutrons and for further biomedical research. The design objectives for the beam holes are to deliver the therapeutic doses in a modest time (30 to 60 min) with minimal fast neutron and gamma contaminants. The n-γ coupling Sn transport calculations have been carried out using n-21 and γ-9 group cross sections on 2-dim. practical models. The calculated results indicate that the design objectives will be achievable even if the thermal power of the reactor is reduced to 1 MW. (author)

  16. Gel dosimeters as useful dose and thermal-fluence detectors in Boron Neutron Capture Therapy (BNCT)

    International Nuclear Information System (INIS)

    Gambarini, G.; Valente, M.; Moss, R.L.; Daquino, G.G.; Nievaart, V.A.; Mariani, M.; Vanossi, E.; Carrara, M.

    2006-01-01

    The dosimetry method based on Fricke-Xylenol-Orange-infused gels in form of layers has shown noticeable potentiality for in-phantom or in-free-beam dose and thermal flux profiling and imaging in the high fluxes of thermal or epithermal neutrons utilised for boron neutron capture therapy (BNCT). Gel-dosimeters in form of layers give the possibility not only of obtaining spatial dose distributions but also of achieving measurements of each dose contribution in neutron fields. The discrimination of the various dose components is achieved by means of pixel-to-pixel manipulations of pairs of images obtained with gel-dosimeters having different isotopic composition. It is possible to place large dosimeters, detecting in such a way large dose images, because the layer geometry of dosimeters avoids sensitive variation of neutron transport due to the gel isotopic composition. Some results obtained after the last improvements of the method are reported. (Author)

  17. Application of drug delivery system for boron neutron capture therapy. Basic research toward clinical application

    International Nuclear Information System (INIS)

    Yanagie, Hironobu; Takahashi, Hiroyuki

    2010-01-01

    Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10 B and thermal neutrons ( 10 B+ 1 n → 7 Li+ 4 He (α) +2.31 MeV (93.7%)/2.79 MeV (6.3%)). The resulting lithium ions and αparticles are high linear energy transfer (LET) particles which give high biological effect. Their short range in tissue (5-9 μm) restricts radiation damage to those cells in which boron atoms are located at the time of neutron irradiation. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer and hepatoma etc, recently. Sodium borocaptate (Na 2 10 B 12 H 11 SH; BSH) and borono-phenylalanine ( 10 BPA) are currently being used in clinical treatments. To achieve the selective delivery of boron atoms to cancer cells, drug delivery system (DDS) becomes an attractive intelligent technology as targeting and controlled release of drugs. We have firstly reported that 10 B atoms delivered by immunoliposomes are cytotoxic to human pancreatic carcinoma cells (AsPC-1) after thermal neutron irradiation in vitro. The intra-tumoural injection of boronated immunoliposomes can increase the retention of 10 B atoms in tumour cells, causing suppression of tumour growth in vivo following thermal neutron irradiation. We prepared polyethylene-glycol binding liposomes (PEG-liposomes) as an effective 10 B carrier to obviate phagocytosis by reticuloendotherial systems. We had prepared 10 BSH entrapped Water-in-Oil-in-Water (WOW) emulsion. The 10 B concentration in VX-2 tumour after intra-arterial injection of 10 BSH entrapped WOW emulsion was superior to the groups of 10 BSH entrapped conventional Lipiodol mix emulsion. 10 Boron entrapped WOW emulsion is one of the most useful for intra-arterial boron delivery carrier on BNCT to hepatocellular carcinoma. (author)

  18. Meeting the challenge of homogenous boron targeting of heterogeneous tumors for effective boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    Heber, Elisa M.; Trivillin, Veronica A.; Itoiz, Maria E.; Rebagliati, J. Raul; Batistoni, Daniel; Kreimann, Erica L.; Schwint, Amanda E.; Nigg, David W.; Gonzalez, Beatriz N.

    2006-01-01

    BNCT is a tumor cell targeted radiation therapy. Inadequately boron targeted tumor populations jeopardize tumor control. Meeting the to date unresolved challenge of homogeneous targeting of heterogeneous tumors with effective boron carriers would contribute to therapeutic efficacy. The aim of the present study was to evaluate the degree of variation in boron content delivered by boronophenylalanine (BPA), GB-10 (Na 2 10 B 10 H 10 ) and the combined administration of (BPA+GB-10) in different portions of tumor, precancerous tissue around tumor and normal pouch tissue in the hamster cheek pouch oral cancer model. Boron content was evaluated by ICP-AES. The degree of homogeneity in boron targeting was assessed in terms of the coefficient of variation ([S.D./Mean]x100) of boron values. Statistical analysis of the results was performed by one-way ANOVA and the least significant difference test. GB-10 and GB-10 plus BPA achieved respectively a statistically significant 1.8-fold and 3.3-fold increase in targeting homogeneity over BPA. The combined boron compound administration protocol contributes to homogeneous targeting of heterogeneous tumors and would increase therapeutic efficacy of BNCT by exposing all tumor populations to neutron capture reactions in boron. (author)

  19. Comparative assessment of single-dose and fractionated boron neutron capture therapy

    International Nuclear Information System (INIS)

    Coderre, J.A.; Micca, P.L.; Fisher, C.D.

    1995-01-01

    The effects of fractionating boron neutron capture therapy (BNCT) were evaluated in the intracerebral rat 9L gliosarcoma and rat spinal cord models using the Brookhaven Medical Research Reactor (BMRR) thermal neutron beam. The amino acid analog p-boronophenylalanine (BPA) was administered prior to each exposure to the thermal neutron beam. The total physical absorbed dose to the tumor during BNCT using BPA was 91% high-linear energy transfer (LET) radiation. Two tumor doses of 5.2 Gy spaced 48 h apart (n = 14) or three tumor doses of 5.2 Gy, each separated by 48 h (n = 10), produced 50 and 60% long-term (>1 year) survivors, respectively. The outcome of neither the two nor the three fractions of radiation was statistically different from that of the corresponding single-fraction group. In the rat spinal cord, the ED 50 for radiation myelopathy (as indicated by limb paralysis within 7 months) after exposure to the thermal beam alone was 13.6 ± 0.4 Gy. Dividing the beam-only irradiation into two or four consecutive daily fractions increased the ED 50 to 14.7 ± 0.2 Gy and 15.5 ± 0.4 Gy, respectively. Thermal neutron irradiation in the presence of BPA resulted in an ED 50 for myelopathy of 13.8 ± 0.6 Gy after a single fraction and 14.9 ± 0.9 Gy after two fractions. An increase in the number of fractions to four resulted in an ED 50 of 14.3 ± 0.6 Gy. The total physical absorbed dose to the blood in the vasculature of the spinal cord during BNCT using BPA was 80% high-LET radiation. It was observed that fractionation was of minor significance in the amelioration of damage to the normal central nervous system in the rat after boron neutron capture irradiation. 30 refs., 5 figs., 3 tabs

  20. Single photon image from PET with insertable collimator for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Jung, Jooyoung; Suh, Tae Suk; Hong, Key Jo

    2014-01-01

    Boron neutron capture therapy (BNCT) is a radiation therapy technique for treating deep-seated brain tumors by irradiation with a thermal neutron in which boron-labelled low molecular weight compounds. Once completed, a single photon emission computed tomography (SPECT) scan is conducted to investigate for the region of therapy using an isotope exclusive to SPECT. In the case of an existing PET/SPECT combination system, at least two types of isotopes should be used for each scan with their purposes. Recently, researchers examined the effects of PET/SPECT dual modality on animal imaging systems. They reported that the PET/SPECT combination system was effective for simultaneous achievement of a single event and coincidence. The aim of our proposed system is to confirm the feasibility of extraction of two types of images from one PET module with an insertable collimator for brain tumor treatment during the BNCT. We attempted to acquire the PET and SPECT images simultaneously using only PET without an additional isotope. Single photon images were acquired using an insertable collimator on a PET detector

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

    International Nuclear Information System (INIS)

    Hawthorne, M. Frederick

    2005-01-01

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

    Energy Technology Data Exchange (ETDEWEB)

    Hawthorne, M. Frederick [Univ. of California, Los Angeles, CA (United States)

    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

  3. Optimization of neutron flux using fission converter plates for Boron Neutron Capture Therapy study in Tehran reactor

    International Nuclear Information System (INIS)

    Hamidi, S.; Babaei, H.

    2003-01-01

    Boron Neutron Capture Therapy is a binary from of radiation therapy for treatment of deep seated brain tumor, based on the nuclear reaction that occur when boron ( 10 B) is exposed to the thermal neutrons. The stable isotope 10 B is irradiated with low energy or thermal neutrons to yield 4 He nuclei (i.e a particles) and recoiling 7 Li ions. These are absorbed in tumor cells and released their energy in them and destroy tumor cells. This work has tried to optimize neutron flux from Tehran reactor in order to be used in a Boron Neutron Capture Therapy program. Fission converter plates (20% enriched Uranium) have been applied to increase the neutron flux

  4. Selective uptake of p-boronophenylalanine by osteosarcoma cells for boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferrari, C. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy)], E-mail: ferraric@unipv.it; Zonta, C.; Cansolino, L.; Clerici, A.M.; Gaspari, A. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy); Altieri, S.; Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics of University, Via Bassi, 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi, 6, Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics of University, Via Bassi, 6, Pavia (Italy); Dionigi, P.; Zonta, A. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy)

    2009-07-15

    Osteosarcoma is the most common non-hematologic primary cancer type that develops in bone. Current osteosarcoma treatments combine multiagent chemotherapy with extensive surgical resection, which in some cases makes necessary the amputation of the entire limb. Nevertheless its infiltrative growth leads to a high incidence of local and distant recurrences that reduce the percentage of cured patients to less than 60%. These poor data required to set up a new therapeutic approach aimed to restrict the surgical removal meanwhile performing a radical treatment. Boron neutron capture therapy (BNCT), a particular radiotherapy based on the nuclear capture and fission reactions by atoms of {sup 10}B, when irradiated with thermal neutrons, could be a valid alternative or integrative option in case of osteosarcoma management, thanks to its peculiarity in selectively destroying neoplastic cells without damaging normal tissues. Aim of the present work is to investigate the feasibility of employing BNCT to treat the limb osteosarcoma. Boronophenylalanine (BPA) is used to carry {sup 10}B inside the neoplastic cells. As a first step the endocellular BPA uptake is tested in vitro on the UMR-106 osteosarcoma cell line. The results show an adequate accumulation capability. For the in vivo experiments, an animal tumor model is developed in Sprague-Dawley rats by means of an intrafemoral injection of UMR-106 cells at the condyle site. The absolute amounts of boron loading and the tumor to normal tissue {sup 10}B ratio are evaluated 2 h after the i.v. administration of BPA. The boron uptake by the neoplastic tissue is almost twice the normal one. However, higher values of boron concentration in tumor are requested before upholding BNCT as a valid therapeutic option in the treatment of osteosarcoma.

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

    International Nuclear Information System (INIS)

    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 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 3 composite and a stacked Al/Teflon design) at various incident electron energies

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

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Hannah E. [Georgia Inst. of Technology, Atlanta, GA (United States)

    1996-04-01

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

  7. Boron Neutron Capture Therapy activity of diffused tumors at TRIGA Mark II in Pavia

    International Nuclear Information System (INIS)

    Bortolussi, S.; Stella, S.; De Bari, A.; Altieri, S.; Bruschi, P.; Bakeine, J.G.; Clerici, A.; Ferrari, C.; Zonta, C.; Zonta, A.; Nano, R.

    2008-01-01

    The Boron neutron Capture Therapy research in Pavia has a long tradition: it begun more than 20 years ago at the TRIGA Mark II reactor of the University. A technique for the treatment of the hepatic metastases was developed, consisting in explanting the liver treated with 10 B, irradiating it in the thermal column of the reactor, and re-implanting the organ in the patient. In the last years, the possibility of applying BNCT to the lung tumours using epithermal collimated neutron beams and without explanting the organ, is being explored. The principal obtained results of the BNCT research will be presented, with particular emphasis on the following aspects: a) the project of a new thermal column configuration to make the thermal neutron flux more uniform inside the explanted liver, b) the Monte Carlo study by means of the MCNP code of the thermal neutron flux distribution inside a patient's thorax irradiated with epithermal neutrons, and c) the measurement of the boron concentration in tissues by (n,α) spectroscopy and neutron autoradiography. (authors)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  9. Computational assessment of improved cell-kill by gadolinium-supplemented boron neutron capture therapy

    Science.gov (United States)

    Culbertson, Christopher N.; Jevremovic, Tatjana

    2003-12-01

    Potential improvement in neutron capture therapy (NCT) by utilizing both 157Gd and 10B is assessed considering two parameters calculated in transport models in MCNP4B, the dose to quiescent cells and the therapeutic ratio. Improved sterilization of quiescent or more generally non-uptaking cells is demonstrated with the addition of 157Gd to conventional 10B loading. The improved dose delivery to non-uptaking cells from concurrent administration of 157Gd and 10B is weighed against a second index, degradation in the therapeutic ratio resulting from the longer interaction lengths of the 157Gd capture products. Optimal concentrations of 157Gd are determined considering varying assumptions for boron uptake levels and selectivity. By analysing the dosimetry results of varying 157Gd concentrations applied concurrently with BPA-delivered boron in NCT, this work seeks to determine a balance between the high tumour-specific dose provided by BPA and the high dose to quiescent cells provided by potential gadolinium agents. Depending upon the assumptions for drug specificity, tumour size and fraction of quiescent cells, NCT with low levels of 157Gd (125 µg g-1) supplementing 10B loadings was shown to be superior to treatments applying 10B alone.

  10. Basic and clinical study of boron neutron capture therapy for malignant brain tumor

    Energy Technology Data Exchange (ETDEWEB)

    Nose, Tadao; Matsumura, Akira; Nakai, Kei; Nakagawa, Kunio; Yoshii, Yoshihiko [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Shibata, Yasushi; Yamamoto, Tetsuya; Hayakawa, Yoshinori; Yamada, Takashi

    1998-01-01

    Rat malignant cells (9L glioma cell) were exposed to neutron radiation after culturing with boron compounds; BSH and STA-BX909, and cell growing ability after the exposure was determined by colony forming assay. The effects of in vivo radiation were examined by measuring neutron flux levels in rat brain and skin aiming to use neutron radiation in clinical study. STA-BX909 was found to show a dose-dependent cell toxicity, which was higher than that of BSH. The radiation induced G2/M block in 9L-glioma cells and their cell cycles recovered thereafter in low-dose radiated cells, but high-dose radiated cells became aneuploidy. Furthermore, boron neutron capture therapy (BNCT) was applied in two patients, 41-year old woman with glioma grade 3 recurred and 45-year old man with glioblastoma multiforme. The former died from systemic deterioration due to ileus, but BNCT was made only one time although conventional radiotherapy is carried out for a relatively long period. Therefore, BNCT was thought to be beneficial from an aspect of `quality of life` and the effects to repress a recurrence of cancer also seemed larger than the conventional one. (M.N.)

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

    Science.gov (United States)

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

    2015-01-01

    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. 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. 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). 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.

  12. Application of generalized perturbation theory to sensitivity analysis in boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Vanessa S. [Universidade Federal Fluminense (EEIMVR/UFF-RJ), Volta Redonda, RJ (Brazil). Escola de Engenharia Industrial e Metalurgica. Programa de Pos-Graduacao em Modelagem Computacional em Ciencia e Tecnologia; Silva, Fernando C.; Silva, Ademir X., E-mail: fernando@con.ufrj.b, E-mail: ademir@con.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (PEN/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Alvarez, Gustavo B. [Universidade Federal Fluminense (EEIMVR/UFF-RJ), Volta Redonda, RJ (Brazil). Escola de Engenharia Industrial e Metalurgica. Dept. de Ciencias Exatas

    2011-07-01

    Boron neutron capture therapy - BNCT - is a binary cancer treatment used in brain tumors. The tumor is loaded with a boron compound and subsequently irradiated by thermal neutrons. The therapy is based on the {sup 10}B (n, {alpha}) {sup 7}Li nuclear reaction, which emits two types of high-energy particles, {alpha} particle and the {sup 7}Li nuclei. The total kinetic energy released in this nuclear reaction, when deposited in the tumor region, destroys the cancer cells. Since the success of the BNCT is linked to the different selectivity between the tumor and healthy tissue, it is necessary to carry out a sensitivity analysis to determinate the boron concentration. Computational simulations are very important in this context because they help in the treatment planning by calculating the lowest effective absorbed dose rate to reduce the damage to healthy tissue. The objective of this paper is to present a deterministic method based on generalized perturbation theory (GPT) to perform sensitivity analysis with respect to the {sup 10}B concentration and to estimate the absorbed dose rate by patients undergoing this therapy. The advantage of the method is a significant reduction in computational time required to perform these calculations. To simulate the neutron flux in all brain regions, the method relies on a two-dimensional neutron transport equation whose spatial, angular and energy variables are discretized by the diamond difference method, the discrete ordinate method and multigroup formulation, respectively. The results obtained through GPT are consistent with those obtained using other methods, demonstrating the efficacy of the proposed method. (author)

  13. Application of generalized perturbation theory to sensitivity analysis in boron neutron capture therapy

    International Nuclear Information System (INIS)

    Garcia, Vanessa S.; Silva, Fernando C.; Silva, Ademir X.; Alvarez, Gustavo B.

    2011-01-01

    Boron neutron capture therapy - BNCT - is a binary cancer treatment used in brain tumors. The tumor is loaded with a boron compound and subsequently irradiated by thermal neutrons. The therapy is based on the 10 B (n, α) 7 Li nuclear reaction, which emits two types of high-energy particles, α particle and the 7 Li nuclei. The total kinetic energy released in this nuclear reaction, when deposited in the tumor region, destroys the cancer cells. Since the success of the BNCT is linked to the different selectivity between the tumor and healthy tissue, it is necessary to carry out a sensitivity analysis to determinate the boron concentration. Computational simulations are very important in this context because they help in the treatment planning by calculating the lowest effective absorbed dose rate to reduce the damage to healthy tissue. The objective of this paper is to present a deterministic method based on generalized perturbation theory (GPT) to perform sensitivity analysis with respect to the 10 B concentration and to estimate the absorbed dose rate by patients undergoing this therapy. The advantage of the method is a significant reduction in computational time required to perform these calculations. To simulate the neutron flux in all brain regions, the method relies on a two-dimensional neutron transport equation whose spatial, angular and energy variables are discretized by the diamond difference method, the discrete ordinate method and multigroup formulation, respectively. The results obtained through GPT are consistent with those obtained using other methods, demonstrating the efficacy of the proposed method. (author)

  14. Gadolinium neutron capture therapy

    International Nuclear Information System (INIS)

    Akine, Yasuyuki; Tokita, Nobuhiko; Tokuuye, Koichi; Satoh, Michinao; Churei, Hisahiko

    1993-01-01

    Gadolinium neutron capture therapy makes use of photons and electrons produced by nuclear reactions between gadolinium and lower-energy neutrons which occur within the tumor. The results of our studies have shown that its radiation effect is mostly of low LET and that the electrons are the significant component in the over-all dose. The dose from gadolinium neutron capture reactions does not seem to increase in proportion to the gadolinium concentration, and the Gd-157 concentration of about 100 μg/ml appears most optimal for therapy. Close contact between gadolinium and the cell is not necessarily required for cell inactivation, however, the effect of electrons released from intracellular gadolinium may be significant. Experimental studies on tumor-bearing mice and rabbits have shown that this is a very promising modality though further improvements in gadolinium delivery to tumors are needed. (author)

  15. Neutron capture therapy for melanoma

    International Nuclear Information System (INIS)

    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

  16. Neutron capture therapy for melanoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Boron-neutron capture therapy for incurable cancer and inoperable brain tumors

    International Nuclear Information System (INIS)

    Hatanaka, Hiroshi

    1993-01-01

    Recent advances in cancer diagnosis and treatment have not yet improved the survival rate of patients with cancers of the brain, liver, etc. In these organs, an extirpation of the organ, which can be done for stomach, breast, cervix, lung, etc. is not allowed, and this fact is the cause of poor therapeutic results. Boron-neutron capture therapy (BNCT) utilizes the nuclear reaction which will take place between the boron-10 (loaded in the cancer cells artificially) and the thermal neutrons (delivered by reactors). The secondary radiations, helium and lithium hit the cancer cell itself and cause the death of the cancer cell while sparing the surrounding normal cells. BNCT is now being tried also by Oda of Kyoto University (9 cases) and by Nakagawa of Tokushima University (7 cases). It has been tried by Mishima (Kobe University) on 12 skin melanoma patients, proving satisfactory local control of the melanomas. Mercaptoundecahydrododecaborate (BHS) and boronophenylalanine (BPA) have been tried for brain tumors and for melanoma. For cancers of the liver and abdominal viscerae, antibody to the tumor specific antigen has been considered a good carrier of boron-10. Surgeons Takahashi, Fujii, Fujii, Yanagie, and Sekiguchi and immunologist Nariuchi of Tokyo University have been involved in the research and have obtained encouraging results in animals. Hatanaka has been proving good effect of BNCT upon giant cerebral arteriovenous malformation (AVM) and skull base meningioma. These diseases, although pathologically benign, have posed difficult problems in neurosurgery. It will be exciting good news to the patients. In conclusion, BNCT appears to be a good means to treat difficult lesions in the brain and other organs which defy sophisticated modern therapeutic means. (author)

  18. Perspectives of boron-neutron capture therapy of malignant brain tumors

    Science.gov (United States)

    Kanygin, V. V.; Kichigin, A. I.; Krivoshapkin, A. L.; Taskaev, S. Yu.

    2017-09-01

    Boron neutron capture therapy (BNCT) is characterized by a selective effect directly on the cells of malignant tumors. The carried out research showed the perspective of the given kind of therapy concerning malignant tumors of the brain. However, the introduction of BNCT into clinical practice is hampered by the lack of a single protocol for the treatment of patients and the difficulty in using nuclear reactors to produce a neutron beam. This problem can be solved by using a compact accelerator as a source of neutrons, with the possibility of installation in a medical institution. Such a neutron accelerator for BNCT was developed at Budker Institute of Nuclear Physics, Novosibirsk. A neutron beam was obtained on this accelerator, which fully complies with the requirements of BNCT, as confirmed by studies on cell cultures and experiments with laboratory animals. The conducted experiments showed the relative safety of the method with the absence of negative effects on cell cultures and living organisms, and also confirmed the effectiveness of BNCT for malignant brain tumors.

  19. Accelerator based-boron neutron capture therapy (BNCT)-clinical QA and QC

    International Nuclear Information System (INIS)

    Suzuki, Minoru; Tanaka, Hiroki; Sakurai, Yoshinori; Yong, Liu; Kashino, Genro; Kinashi, Yuko; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira

    2009-01-01

    Alpha-particle and recoil Li atom yielded by the reaction ( 10 B, n), due to their high LET properties, efficiently and specifically kill the cancer cell that has incorporated the boron. Efficacy of this boron neutron capture therapy (BNCT) has been demonstrated mainly in the treatment of recurrent head/neck and malignant brain cancers in Kyoto University Research Reactor Institute (KUR). As the clinical trial of BNCT is to start from 2009 based on an accelerator (not on the Reactor), this paper describes the tentative outline of the standard operation procedure of BNCT for its quality assurance (QA) and quality control (QC) along the flow of its clinical practice. Personnel concerned in the practice involve the attending physician, multiple physicians in charge of BNCT, medical physicists, nurses and reactor stuff. The flow order of the actual BNCT is as follows: Pre-therapeutic evaluation mainly including informed consent and confirmation of the prescription; Therapeutic planning including setting of therapy volume, and of irradiation axes followed by meeting for stuffs' agreement, decision of irradiating field in the irradiation room leading to final decision of the axis, CT for the planning, decision of the final therapeutic plan according to Japan Atomic Energy Agency-Computational Dosimetry System (JCDS) and meeting of all related personnel for the final confirmation of therapeutic plan; and BNCT including the transport of patient to KUR, dripping of boronophenylalanine, setting up of the patient on the machine, blood sampling for pharmacokinetics, boron level measurement for decision of irradiating time, switch on/off of the accelerator, confirmation of patient's movement in the irradiated field after the neutron irradiation, blood sampling for confirmation of the boron level, and patient's leave from the room. The QA/QC check is principally to be conducted with the two-person rule. The purpose of the clinical trial is to establish the usefulness of BNCT

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  1. Boron Neutron Capture Therapy at European research reactors - Status and perspectives

    International Nuclear Information System (INIS)

    Moss, R.L.

    2004-01-01

    Over the last decade. there has been a significant revival in the development of Boron Neutron Capture Therapy (BNCT) as a treatment modality for curing cancerous tumours, especially glioblastoma multiforme and subcutaneous malignant melanoma. In 1987 a European Collaboration on BNCT was formed, with the prime task to identify suitable research reactors in Europe where BNCT could be applied. Due to reasons discussed in this paper, the HFR Petten was chosen as the test-bed for demonstrating BNCT. Currently, the European Collaboration is approaching the start of clinical trials, using epithermal neutrons and borocaptate sodium (BSH) as the 10 B delivery agent. The treatment is planned to start in the first half of 1996. The paper here presents an overview on the principle of BNCT, the requirements imposed on a research reactor in order to be considered for BNCT, and the perspectives for other European materials testing reactors. A brief summary on the current status of the work at Petten is given, including: the design, construction and characterisation of the epithermal neutron beam: performance and results of the healthy tissue tolerance study; the development of a treatment planning programme based on the Monte Carlo code MCNP; the design of an irradiation room; and on the clinical trials themselves. (author)

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

    Science.gov (United States)

    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.

  3. Development of the JAERI computational dosimetry system (JCDS) for boron neutron capture therapy. Cooperative research

    CERN Document Server

    Kumada, H; Matsumura, A; Nakagawa, Y; Nose, T; Torii, Y; Uchiyama, J; Yamamoto, K; Yamamoto, T

    2003-01-01

    The Neutron Beam Facility at JRR-4 enables us to carry out boron neutron capture therapy with epithermal neutron beam. In order to make treatment plans for performing the epithermal neutron beam BNCT, it is necessary to estimate radiation doses in a patient's head in advance. The JAERI Computational Dosimetry System (JCDS), which can estimate distributions of radiation doses in a patient's head by simulating in order to support the treatment planning for epithermal neutron beam BNCT, was developed. JCDS is a software that creates a 3-dimentional head model of a patient by using CT and MRI images, and that generates a input data file automatically for calculation of neutron flux and gamma-ray dose distributions in the brain with the Monte Carlo code MCNP, and that displays these dose distributions on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By using CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is...

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

    Energy Technology Data Exchange (ETDEWEB)

    Skalyga, V., E-mail: skalyga.vadim@gmail.com [Institute of Applied Physics, RAS, 46 Ul’yanova st., 603950 Nizhny Novgorod (Russian Federation); Lobachevsky State University of Nizhny Novgorod (UNN), 23 Gagarina st., 603950 Nizhny Novgorod (Russian Federation); Izotov, I.; Golubev, S.; Razin, S. [Institute of Applied Physics, RAS, 46 Ul’yanova st., 603950 Nizhny Novgorod (Russian Federation); Sidorov, A. [Institute of Applied Physics, RAS, 46 Ul’yanova st., 603950 Nizhny Novgorod (Russian Federation); Lobachevsky State University of Nizhny Novgorod (UNN), 23 Gagarina st., 603950 Nizhny Novgorod (Russian Federation); Maslennikova, A. [Lobachevsky State University of Nizhny Novgorod (UNN), 23 Gagarina st., 603950 Nizhny Novgorod (Russian Federation); Nizhny Novgorod State Medical Academy, 10/1 Minina Sq., 603005 Nizhny Novgorod (Russian Federation); Volovecky, A. [Lobachevsky State University of Nizhny Novgorod (UNN), 23 Gagarina st., 603950 Nizhny Novgorod (Russian Federation); Kalvas, T.; Koivisto, H.; Tarvainen, O. [University of Jyvaskyla, Department of Physics, PO Box 35 (YFL), 40500 Jyväskylä (Finland)

    2014-12-21

    Boron-neutron capture therapy (BNCT) is a perspective treatment method for radiation resistant tumors. Unfortunately its development is strongly held back by a several physical and medical problems. Neutron sources for BNCT currently are limited to nuclear reactors and accelerators. For wide spread of BNCT investigations more compact and cheap neutron source would be much more preferable. In present paper an approach for compact D–D neutron generator creation based on a high current ECR ion source is suggested. Results on dense proton beams production are presented. A possibility of ion beams formation with current density up to 600 mA/cm{sup 2} is demonstrated. Estimations based on obtained experimental results show that neutron target bombarded by such deuteron beams would theoretically yield a neutron flux density up to 6·10{sup 10} cm{sup −2}/s. Thus, neutron generator based on a high-current deuteron ECR source with a powerful plasma heating by gyrotron radiation could fulfill the BNCT requirements significantly lower price, smaller size and ease of operation in comparison with existing reactors and accelerators.

  5. FiR 1 reactor in service for boron neutron capture therapy (BNCT) and isotope production

    International Nuclear Information System (INIS)

    Auterinen, I.; Salmenhaara, S.E.J. . Author

    2004-01-01

    The FiR 1 reactor, a 250 kW Triga reactor, has been in operation since 1962. The main purpose for the existence of the reactor is now the Boron Neutron Capture Therapy (BNCT), but FiR 1 has also an important national role in providing local enterprises and research institutions in the fields of industrial measurements, pharmaceuticals, electronics etc. with isotope production and activation analysis services. In the 1990's a BNCT treatment facility was built at the FiR 1 reactor located at Technical Research Centre of Finland. A special new neutron moderator material Fluental TM (Al+AlF3+Li) developed at VTT ensures the superior quality of the neutron beam. Also the treatment environment is of world top quality after a major renovation of the whole reactor building in 1997. Recently the lithiated polyethylene neutron shielding of the beam aperture was modified to ease the positioning of the patient close to the beam aperture. Increasing the reactor power to 500 kW would allow positioning of the patient further away from the beam aperture. Possibilities to accomplish a safety analysis for this is currently under considerations. Over thirty patients have been treated at FiR 1 since May 1999, when the license for patient treatment was granted to the responsible BNCT treatment organization, Boneca Corporation. Currently three clinical trial protocols for tumours in the brain as well as in the head and neck region are recruiting patients. (author)

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

    Science.gov (United States)

    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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Long term outcome of boron neutron capture therapy for malignant melanoma

    International Nuclear Information System (INIS)

    Hiratsuka, J.; Fukuda, H.; Kobayashi, T.; Yoshino, K.; Honda, C.; Ichihashi, M.; Mishima, Y.

    2000-01-01

    Eighteen patients with cutaneous malignant melanoma were treated by boron neutron capture therapy (BNCT) using 10 B-BPA. Our aim was to assess the long term clinical outcome of BNCT on these patients. The target areas were 15 primary lesions and 5 metastatic lesions. The primary lesions were consisted of acral lentigious melanoma (ALM) in six patients, nodular melanoma (NM) in six and lentigo maligna melanoma (LMM) in three. The complete regression (CR) rates were 73% for the primary lesions, 20% for the metastatic lesions. The CR rates for the primary lesions according to melanoma type were 33% for NM and 100% for non-NM. None of the patients with CR showed local recurrence in the radiation field during follow up ranging from 5.5 to 10.6 years (mean 6.7 years). The five year cause specific survival rate was 92% in the cases without distant metastasis at the time of BNCT. BNCT proves to be a very useful therapeutic modality for the management of cutaneous malignant melanoma. (author)

  8. Long term outcome of boron neutron capture therapy for malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Hiratsuka, J. [Kawasaki Medical School, Kurashiki, Okayama (Japan); Fukuda, H. [Tohoku Univ., Sendai (Japan); Kobayashi, T. [Kyoto Univ. (Japan); Yoshino, K. [Shinshu Univ., Matsumoto, Nagano (Japan); Honda, C.; Ichihashi, M. [Kobe Univ., Kobe, Hyogo (Japan); Mishima, Y. [Mishima Institute for Dermatological Research, Kobe, Hyogo (Japan)

    2000-10-01

    Eighteen patients with cutaneous malignant melanoma were treated by boron neutron capture therapy (BNCT) using {sup 10}B-BPA. Our aim was to assess the long term clinical outcome of BNCT on these patients. The target areas were 15 primary lesions and 5 metastatic lesions. The primary lesions were consisted of acral lentigious melanoma (ALM) in six patients, nodular melanoma (NM) in six and lentigo maligna melanoma (LMM) in three. The complete regression (CR) rates were 73% for the primary lesions, 20% for the metastatic lesions. The CR rates for the primary lesions according to melanoma type were 33% for NM and 100% for non-NM. None of the patients with CR showed local recurrence in the radiation field during follow up ranging from 5.5 to 10.6 years (mean 6.7 years). The five year cause specific survival rate was 92% in the cases without distant metastasis at the time of BNCT. BNCT proves to be a very useful therapeutic modality for the management of cutaneous malignant melanoma. (author)

  9. Investigation of Isfahan miniature neutron source reactor (MNSR for boron neutron capture therapy by MCNP simulation

    Directory of Open Access Journals (Sweden)

    S.Z Kalantari

    2015-01-01

    Full Text Available One of the important neutron sources for Boron Neutron Capture Therapy (BNCT is a nuclear reactor. It needs a high flux of epithermal neutrons. The optimum conditions of the neutron spectra for BNCT are provided by the International Atomic Energy Agency (IAEA. In this paper, Miniature Neutron Source Reactor (MNSR as a neutron source for BNCT was investigated. For this purpose, we designed a Beam Shaping Assembly (BSA for the reactor and the neutron transport from the core of the reactor to the output windows of BSA was simulated by MCNPX code. To optimize the BSA performance, two sets of parameters should be evaluated, in-air and in-phantom parameters. For evaluating in-phantom parameters, a Snyder head phantom was used and biological dose rate and dose-depth curve were calculated in brain normal and tumor tissues. Our calculations showed that the neutron flux of the MNSR reactor can be used for BNCT, and the designed BSA in optimum conditions had a good therapeutic characteristic for BNCT.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  11. Early effects of boron neutron capture therapy on rat glioma models

    International Nuclear Information System (INIS)

    Nakagawa, N.; Akai, F.; Fukawa, N.; Taneda, M.; Ono, K.; Suzuki, M.

    2006-01-01

    Early effects of boron neutron capture therapy on malignant gliomas are characterized by reduction of the enhanced area regression of the peritumoral edema radiologically. The aim of this study is to investigate the early histological changes of tumors and inflammatory cells after BNCT in the rat brain. The rats were treated with BNCT using boronophenyialanine (BPA) 7 days after implantation of C6 glioma cells. The tumors were assessed their sizes and configurations with magnetic resonance imaging, then killed 4 days after BNCT. The mean tumor volumes were 39mm 3 in BNCT-treated group, and 138 mm 3 in the control group. In the histological examination, tumors of the BNCT group showed less pleomorphic appearance with atypical nuclei and mitotic figures, compared with the control group. Necrosis and edematous changes in the neuropile were negligible. There existed remnant tumors adjacent to the lateral ventricle. The reactions of the inflammatory cells were examined with ED-1 of macrophage marker. ED-1 positive cells and their processes were reduced in the marginal area of tumor in the BNCT group. BNCT reduce the tumor progression by suppression of the proliferation. Inhibition of the activated macrophages may reduce peritumoral edema in early phase. (author)

  12. Effectiveness of boron neutron capture therapy for recurrent head and neck malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Itsuro [Department of Oral and Maxillofacial Surgery, II Osaka University, Graduate School of Dentistry, Osaka (Japan)], E-mail: katoitsu@dent.osaka-u.ac.jp; Fujita, Yusei [Department of Oral and Maxillofacial Surgery, II Osaka University, Graduate School of Dentistry, Osaka (Japan); Maruhashi, Akira [Radiation Oncology Research Laboratory, Research Reactor Institut, Kyoto University, Osaka (Japan); Kumada, Hiroaki [Japan Atomic Energy Agency, Tokai Research and Development Center, Ibaraki (Japan); Ohmae, Masatoshi [Department of Oral and Maxillofacial Surgery, Izimisano Municipal Hospital, Rinku General Hospital, Izumisano, Osaka (Japan); Kirihata, Mitsunori [Graduate School of Environment and Life Science, Osaka prefectural University, Osaka (Japan); Imahori, Yoshio [Department of Neurosurgery, Kyoto Prefectural University, Kyoto (Japan); CEO of Cancer Intelligence Care Systems, Inc., Tokyo (Japan); Suzuki, Minoru [Radiation Oncology Research Laboratory, Research Reactor Institut, Kyoto University, Osaka (Japan); Sakrai, Yoshinori [Graduate School of Medicine, Sapporo Medical University of Medicine, Hokkaido (Japan); Sumi, Tetsuro; Iwai, Soichi; Nakazawa, Mitsuhiro [Department of Oral and Maxillofacial Surgery, II Osaka University, Graduate School of Dentistry, Osaka (Japan); Murata, Isao; Miyamaru, Hiroyuki [Division of Electrical, Electronic and Information Engineering, Graduate School of Engineering, Osaka University (Japan); Ono, Koji [Radiation Oncology Research Laboratory, Research Reactor Institut, Kyoto University, Osaka (Japan)

    2009-07-15

    It is necessary to explore new treatments for recurrent head and neck malignancies (HNM) to avoid severe impairment of oro-facial structures and functions. Boron neutron capture therapy (BNCT) is tumor-cell targeted radiotherapy that has significant superiority over conventional radiotherapies in principle. We have treated with BNCT 42 times for 26 patients (19 squamous cell carcinomas (SCC), 4 salivary gland carcinomas and 3 sarcomas) with a recurrent and far advanced HNM since 2001. Results of (1) {sup 10}B concentration of tumor/normal tissue ratios (T/N ratio) of FBPA-PET studies were SCC: 1.8-5.7, sarcoma: 2.5-4.0, parotid tumor: 2.5-3.7. (2) Therapeutic effects were CR: 12 cases, PR: 10 cases, PD: 3 cases NE (not evaluated): 1 case. Response rate was 85%. (3) Improvement of QOL such as a relief of severe pain, bleeding, and exudates at the local lesion, improvement of PS, disappearance of ulceration, covered with normal skin and preserved oral and maxillofacial functions and tissues. (4) Survival periods after BNCT were 1-72 months (mean: 13.6 months). Six-year survival rate was 24% by Kaplan-Meier analysis. (5) Adverse-events were transient mucositis and alopecia in most of the cases; three osteomyelitis and one brain necrosis were recognized. These results indicate that BNCT represents a new and promising treatment approach for advanced HNM.

  13. Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases in BDIX rats

    International Nuclear Information System (INIS)

    Trivillin, V.A.; Garabalino, M.A.; Colombo, L.L.

    2013-01-01

    Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases in BDIX rats Introduction: Boron Neutron Capture Therapy (BNCT) is based on selective tumor uptake of boron compounds, followed by neutron irradiation. BNCT was proposed for the treatment of unresectable, diffuse lung metastases. The aim of the present study was to perform BNCT studies in an experimental model of lung metastases. Materials and Methods: 3 x 106/0.5 ml colon carcinoma cells (DHD/K12/TRb) were injected iv in syngeneic BDIX rats. Three weeks post-inoculation, rats with diffuse lung metastases were used for in vivo BNCT studies in the RA-3 Nuclear Reactor. Based on previous biodistribution studies and computational dosimetry with Monte Carlo simulation, 2 doses were prescribed, i.e. 4 Gy and 8 Gy minimum absorbed dose to tumor. The animals were assigned to 5 experimental groups (n= 4 to 8) at each dose level: T0 (euthanized pre-treatment), BPA-BNCT, Comb-BNCT (BPA+GB-10), Beam only (background dose) and Sham (same manipulation, no treatment). Boron concentration was measured in a blood sample taken pre-irradiation to verify that the value was in the range established in previous biodistribution studies. The animals were followed clinically for 2 weeks after neutron irradiation and then euthanized to assess the response of tumor and normal lung, macroscopically and histologically. To date we have evaluated the end-point weight of lung (normal lung + metastases) and % lung weight/body weight as an indicator of tumor growth. Results: The statistical analysis (ANOVA) of % lung weight/body weight showed statistically significant differences (p<0.05) between groups T0 (0.79 ± 0.38) and Sham (1.87 ± 0.91). No statistically significant differences were observed between the Beam only groups (at both dose levels) and Sham. Similar and statistically significant tumor control was induced in the groups BPA-BNCT Low dose (LD) (0.56 ± 0.11), BPA-BNCT High dose (HD) (0.80 ± 0.16), Comb

  14. Antiproliferative effect and apoptosis induction in melanoma treatment by boron neutron capture therapy (BCNT)

    Energy Technology Data Exchange (ETDEWEB)

    Faiao-Flores, Fernanda; Coelho, Paulo; Arruda-Neto, Joao; Maria, Durvanei [University of Sao Paulo (USP), SP (Brazil)

    2011-07-01

    Full text: Introduction: Boron neutron capture therapy (BNCT) is an experimental radiotherapy where a compound having {sup 10}B is administered to cancer patients and is accumulated in tumor tissues. Thus, the tumor is irradiated with thermal neutrons, {sup 10}B absorbs and destroys them, producing alpha radiation. Boronophenylalanine (BPA) is the agent responsible for delivering boron to the tumor tissue. After BPA administration, BNCT is used as a localized radiotherapy for many tumors treatment, mainly melanoma, which has a high mortality rate among all types of tumors. The aim of this study was to evaluate in vitro antiproliferative and antitumor effects of BNCT application in human melanoma treatment. Materials and Methods: MEWO cells (human melanoma) were cultured and treated with different concentrations of BPA (8.36 to 0.52 mg/ml). After 90 minutes, they were irradiated with thermal neutron flux up to a dose of 8.4 Gy. The parameters analyzed were free radical production, cell cycle progression, cell death signaling pathways, cycling D1, caspase-3 and extracellular matrix synthesis produced, beyond the mitochondrial electric potential analysis. Results: After BNCT treatment, MEWO cells showed an amount of free radical increase about 10 times. Still, there was a significant decrease of cyclin D1, G0/G1 proliferation, synthesis and G2/M cell cycle phases. BNCT induced a mitochondrial electrical potential decrease, as well as fibrillar proteins of extracellular matrix. BNCT had a significant number of dead cell increase, mainly by necrosis. However, BNCT induced phosphorylated caspase 3 increase. Discussion/Conclusion: BNCT induced cell death increase by necrosis, mitochondrial electric potential decrease and free radical production increase. BNCT is cytotoxic to melanoma cells. Besides necrosis, phosphorylated caspase 3 increase was observed, accompanied by a proliferative response decrease regulated by the G1/S checkpoint and matrix extracellular synthesis

  15. Application of the boron neutron capture therapy to undifferentiated thyroid cancer using two boron compounds (BPA and BOPP)

    International Nuclear Information System (INIS)

    Viaggi, Mabel; Dagrosa, Maria A.; Juvenal, Guillermo J.; Pisarev, Mario A.; Longhino, Juan M.; Blaumann, Hernan R.; Calzetta Larrieu, Osvaldo A.; Kahl, Stephen B.

    2004-01-01

    We have shown the selective uptake of boronophenylalanine (BPA) by undifferentiated thyroid cancer (UTC) human cell line ARO, both in vitro and in vivo. Moreover, a 50% histologic cure of mice bearing the tumor was observed when the complete boron neutron capture therapy was applied. More recently we have analyzed the biodistribution of BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(ba-dihydroxyethyl)-deutero-porphyrin IX) and showed that when BOPP was injected 5 days before BPA, and the animals were sacrificed 60 min after the ip injection of BPA, a significant increase in boron uptake by the tumor was found (38-45ppm with both compounds Vs. 20 ppm with BPA alone). Five days post the ip BOPP injection and 1 hr after BPA, the ratios were: tumor/blood 3,75; tumor /distal skin 2. Other important ratios were tumor/thyroid 6,65 and tumor/lung 3,8. The present studies were performed in mice transplanted with ARO cells and injected with BOPP and BPA. Only in mice treated with the neutron beam and injected with the boronated compounds we observed a 100% control of tumor growth. Two groups of mice received different total absorbed doses: 3.00 and 6.01 Gy, but no further improvement in the outcome was found compared to the previous results using BPA alone (4.3 Gy). (author)

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

    International Nuclear Information System (INIS)

    Kabalka, G. W.

    2005-01-01

    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 pharmacokinetics 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 BNCT agents that could be labeled with radioactive nuclides for the in vivo detection of boron

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Optimal timing of neutron irradiation for boron neutron capture therapy after intravenous infusion of sodium borocaptate in patients with glioblastoma

    International Nuclear Information System (INIS)

    Kageji, Teruyoshi; Nagahiro, Shinji; Kitamura, Katsushi; Nakagawa, Yoshinobu; Hatanaka, Hiroshi; Haritz, Dietrich; Grochulla, Frank; Haselsberger, Klaus; Gabel, Detlef

    2001-01-01

    Purpose: A cooperative study in Europe and Japan was conducted to determine the pharmacokinetics and boron uptake of sodium borocaptate (BSH: Na 2 B 12 H 11 SH), which has been introduced clinically as a boron carrier for boron neutron capture therapy in patients with glioblastoma. Methods and Materials: Data from 56 patients with glioblastoma who received BSH intravenous infusion were retrospectively reviewed. The pharmacokinetics were evaluated in 50 patients, and boron uptake was investigated in 47 patients. Patients received BSH doses between 12 and 100 mg/kg of body weight. For the evaluation, the infused boron dose was scaled linearly to 100 mg/kg BSH. Results: In BSH pharmacokinetics, the average value for total body clearance, distribution volume of steady state, and mean residence time was 3.6±1.5 L/h, 223.3±160.7 L, and 68.0±52.5 h, respectively. The average values of the boron concentration in tumor adjusted to 100 mg/kg BSH, the boron concentration in blood adjusted to 100 mg/kg BSH, and the tumor/blood boron concentration ratio were 37.1±35.8 ppm, 35.2±41.8 ppm, and 1.53±1.43, respectively. A good correlation was found between the logarithmic value of T adj and the interval from BSH infusion to tumor tissue sampling. About 12-19 h after infusion, the actual values for T adj and tumor/blood boron concentration ratio were 46.2±36.0 ppm and 1.70±1.06, respectively. The dose ratio between tumor and healthy tissue peaked in the same interval. Conclusion: For boron neutron capture therapy using BSH administered by intravenous infusion, this work confirms that neutron irradiation is optimal around 12-19 h after the infusion is started

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

    International Nuclear Information System (INIS)

    Moran, J.M.

    1992-02-01

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

  20. The radiobiology of boron neutron capture therapy: Are ''photon-equivalent'' doses really photon-equivalent?

    International Nuclear Information System (INIS)

    Coderre, J.A.; Diaz, A.Z.; Ma, R.

    2001-01-01

    Boron neutron capture therapy (BNCT) produces a mixture of radiation dose components. The high-linear energy transfer (LET) particles are more damaging in tissue than equal doses of low-LET radiation. Each of the high-LET components can multiplied by an experimentally determined factor to adjust for the increased biological effectiveness and the resulting sum expressed in photon-equivalent units (Gy-Eq). BNCT doses in photon-equivalent units are based on a number of assumptions. It may be possible to test the validity of these assumptions and the accuracy of the calculated BNCT doses by 1) comparing the effects of BNCT in other animal or biological models where the effects of photon radiation are known, or 2) if there are endpoints reached in the BNCT dose escalation clinical trials that can be related to the known response to photons of the tissue in question. The calculated Gy-Eq BNCT doses delivered to dogs and to humans with BPA and the epithermal neutron beam of the Brookhaven Medical Research Reactor were compared to expected responses to photon irradiation. The data indicate that Gy-Eq doses in brain may be underestimated. Doses to skin are consistent with the expected response to photons. Gy-Eq doses to tumor are significantly overestimated. A model system of cells in culture irradiated at various depths in a lucite phantom using the epithermal beam is under development. Preliminary data indicate that this approach can be used to detect differences in the relative biological effectiveness of the beam. The rat 9L gliosarcoma cell survival data was converted to photon-equivalent doses using the same factors assumed in the clinical studies. The results superimposed on the survival curve derived from irradiation with Cs-137 photons indicating the potential utility of this model system. (author)

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

    Science.gov (United States)

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

    2014-12-01

    Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high LET radiation. It consists in the enrichment of tumour with (10)B and in the successive irradiation of the target with low energy neutrons producing charged particles that mainly cause non-repairable damages to the cells. The feasibility to treat Non Small Cells Lung Cancer (NSCLC) with BNCT was explored. This paper proposes a new approach to determine treatment plans, introducing the possibility to choose the irradiation start and duration to maximize the tumour dose. A Tumour Control Probability (TCP) suited for lung BNCT as well as other high dose radiotherapy schemes was also introduced. Treatment plans were evaluated in localized and disseminated lung tumours. Semi-ideal and real energy spectra beams were employed to assess the best energy range and the performance of non-tailored neutron sources for lung tumour treatments. The optimal neutron energy is within [500 eV-3 keV], lower than the 10 keV suggested for the treatment of deep-seated tumours in the brain. TCPs higher than 0.6 and up to 0.95 are obtained for all cases. Conclusions drawn from [Suzuki et al., Int Canc Conf J 1 (4) (2012) 235-238] supporting the feasibility of BNCT for shallow lung tumours are confirmed, however discussions favouring the treatment of deeper lesions and disseminated disease are also opened. Since BNCT gives the possibility to deliver a safe and potentially effective treatment for NSCLC, it can be considered a suitable alternative for patients with few or no treatment options. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Dynamic infrared imaging for cancer: research and development in the Argentine Boron neutron capture therapy

    International Nuclear Information System (INIS)

    Santa Cruz, Gustavo A.; Bertotti, J.; Marin, J.

    2009-01-01

    In the framework of the Argentine Boron Neutron Capture Therapy (BNCT) project for treating metastatic cutaneous melanoma, we have initiated a research and development program aimed at obtaining a noninvasive methodology for following-up the treated patients. The technique is called Dynamic Infrared Imaging (DIRI) and comprises the acquisition of infrared images as a function of time of the anatomical part under study, when the region is subjected to a mild cold stress. Vascular, metabolic and regulating differences between normal and tumor tissues appear as differences in the pattern of temperature evolution, which can be correlated with the anatomical and functional aspects of both. Two patients enrolled in the BNCT protocol were studied with DIRI. A good spatial correlation between dose, temperature recovery velocity and skin reaction distributions was observed at the time of maximum expression of the erythematous reaction. Melanoma nodules appear as highly localized hyperthermic regions, surrounded and interconnected by elevated temperature areas. Their temperature recovery velocity after the thermal cold stress was substantially faster than that of normal skin with an appreciably large temperature difference (6 degreesC to 10 degreesC). These tissue differences can be related with the thermal conductivity and metabolic rate as explained by a simple one-directional heat transport model. Compared with other imaging modalities (CT and Doppler ultrasound) DIRI has had a similar ability for confirming the already diagnosed nodules. Together with the clinical observation, DIRI provides a potentially useful amount of information, at a competitive cost-benefit relationship suitable for performing a non-invasive functional assessment of this kind of cutaneous lesions and the evaluation of the acute skin reaction following irradiation. (author)

  4. Dosimetric analysis of BNCT - Boron Neutron Capture Therapy - coupled to 252Cf brachytherapy

    International Nuclear Information System (INIS)

    Brandao, Samia F.; Campos, Tarcisio P.R.

    2009-01-01

    The incidence of brain tumors is increasing in world population; however, the treatments employed in this type of tumor have a high rate of failure and in some cases have been considered palliative, depending on histology and staging of tumor. Its necessary to achieve the control tumor dose without the spread irradiation cause damage in the brain, affecting patient neurological function. Stereotactic radiosurgery is a technique that achieves this; nevertheless, other techniques that can be used on the brain tumor control must be developed, in order to guarantee lower dose on health surroundings tissues other techniques must be developing. The 252 Cf brachytherapy applied to brain tumors has already been suggested, showing promising results in comparison to photon source, since the active source is placed into the tumor, providing greater dose deposition, while more distant regions are spared. BNCT - Boron Neutron Capture Therapy - is another technique that is in developing to brain tumors control, showing theoretical superiority on the rules of conventional treatments, due to a selective irradiation of neoplasics cells, after the patient receives a borate compound infusion and be subjected to a epithermal neutrons beam. This work presents dosimetric studies of the coupling techniques: BNCT with 252 Cf brachytherapy, conducted through computer simulation in MCNP5 code, using a precise and well discretized voxel model of human head, which was incorporated a representative Glioblastoma Multiform tumor. The dosimetric results from MCNP5 code were exported to SISCODES program, which generated isodose curves representing absorbed dose rate in the brain. Isodose curves, neutron fluency, and dose components from BNCT and 252 Cf brachytherapy are presented in this paper. (author)

  5. Development of the JAERI computational dosimetry system (JCDS) for boron neutron capture therapy. Cooperative research

    Energy Technology Data Exchange (ETDEWEB)

    Kumada, Hiroaki; Yamamoto, Kazuyoshi; Torii, Yoshiya; Uchiyama, Junzo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Matsumura, Akira; Yamamoto, Tetsuya; Nose, Tadao [Tsukuba Univ., Tsukuba, Ibaraki (Japan); Nakagawa, Yoshinobu [National Sanatorium Kagawa-Children' s Hospital, Kagawa (Japan); Kageji, Teruyoshi [Tokushima Univ., Tokushima (Japan)

    2003-03-01

    The Neutron Beam Facility at JRR-4 enables us to carry out boron neutron capture therapy with epithermal neutron beam. In order to make treatment plans for performing the epithermal neutron beam BNCT, it is necessary to estimate radiation doses in a patient's head in advance. The JAERI Computational Dosimetry System (JCDS), which can estimate distributions of radiation doses in a patient's head by simulating in order to support the treatment planning for epithermal neutron beam BNCT, was developed. JCDS is a software that creates a 3-dimentional head model of a patient by using CT and MRI images, and that generates a input data file automatically for calculation of neutron flux and gamma-ray dose distributions in the brain with the Monte Carlo code MCNP, and that displays these dose distributions on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By using CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is able to be made easily. The three-dimensional head image is editable to simulate the state of a head after its surgical processes such as skin flap opening and bone removal in the BNCT with craniotomy that are being performed in Japan. JCDS can provide information for the Patient Setting System which can support to set the patient to an actual irradiation position swiftly and accurately. This report describes basic design of JCDS and functions in several processing, calculation methods, characteristics and performance of JCDS. (author)

  6. Research of accelerator-based neutron source for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Li Changkai; Ma Yingjie; Tang Xiaobin; Xie Qin; Geng Changran; Chen Da

    2013-01-01

    Background: 7 Li (p, n) reaction of high neutron yield and low threshold energy has become one of the most important neutron generating reactions for Accelerator-based Boron Neutron Capture Therapy (BNCT). Purpose Focuses on neutron yield and spectrum characteristics of this kind of neutron generating reaction which serves as an accelerator-based neutron source and moderates the high energy neutron beams to meet BNCT requirements. Methods: The yield and energy spectrum of neutrons generated by accelerator-based 7 Li(p, n) reaction with incident proton energy from 1.9 MeV to 3.0 MeV are researched using the Monte Carlo code-MCNPX2.5.0. And the energy and angular distribution of differential neutron yield by 2.5-MeV incident proton are also given in this part. In the following part, the character of epithermal neutron beam generated by 2.5-MeV incident protons is moderated by a new-designed moderator. Results: Energy spectra of neutrons generated by accelerator-based 7 Li(p, n) reaction with incident proton energy from 1.9 MeV to 3.0 MeV are got through the simulation and calculation. The best moderator thickness is got through comparison. Conclusions: Neutron beam produced by accelerator-based 7 Li(p, n) reaction, with the bombarding beam of 10 mA and the energy of 2.5 MeV, can meet the requirement of BNCT well after being moderated. (authors)

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

    International Nuclear Information System (INIS)

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

    1990-01-01

    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

  8. General Electric PETtrace cyclotron as a neutron source for boron neutron capture therapy

    Science.gov (United States)

    Bosko, Andrey

    This research investigates the use of a PETtrace cyclotron produced by General Electric (GE) as a neutron source for boron neutron capture therapy (BNCT). The GE PETtrace was chosen for this investigation because this type of cyclotron is popular among nuclear pharmacies and clinics in many countries; it is compact and reliable; it produces protons with energies high enough to produce neutrons with appropriate energy and fluence rate for BNCT and it does not require significant changes in design to provide neutrons. In particular, the standard PETtrace 18O target is considered. The cyclotron efficiency may be significantly increased if unused neutrons produced during radioisotopes production could be utilized for other medical modalities such as BNCT at the same time. The resulting dose from the radiation emitted from the target is evaluated using the Monte Carlo radiation transport code MCNP at several depths in a brain phantom for different scattering geometries. Four different moderating materials of various thicknesses were considered: light water, carbon, heavy water, arid Fluental(TM). The fluence rate tally was used to calculate photon and neutron dose, by applying fluence rate-to-dose conversion factors. Fifteen different geometries were considered and a 30-cm thick heavy water moderator was chosen as the most suitable for BNCT with the GE PETtrace cyclotron. According to the Brookhaven Medical Research Reactor (BMRR) protocol, the maximum dose to the normal brain is set to 12.5 RBEGy, which for the conditions of using a heavy water moderator, assuming a 60 muA beam current, would be reached with a treatment time of 258 min. Results showed that using a PETtrace cyclotron in this configuration provides a therapeutic ratio of about 2.4 for depths up to 4 cm inside a brain phantom. Further increase of beam current proposed by GE should significantly improve the beam quality or the treatment time and allow treating tumors at greater depths.

  9. The 3D tomographic image reconstruction software for prompt-gamma measurement of the boron neutron capture therapy

    International Nuclear Information System (INIS)

    Morozov, Boris; Auterinen, Iiro; Kotiluoto, Petri; Kortesniemi, Mika

    2006-01-01

    A tomographic imaging system based on the spatial distribution measurement of the neutron capture reaction during Boron Neutron Capture Therapy (BNCT) would be very useful for clinical purpose. Using gamma-detectors in a 2D-panel, boron neutron capture and hydrogen neutron capture gamma-rays emitted by the neutron irradiated region can be detected, and an image of the neutron capture events can be reconstructed. A 3D reconstruction software package has been written to support the development of a 3D prompt-gamma tomographic system. The package consists of three independent modules: phantom generation, reconstruction and evaluation modules. The reconstruction modules are based on algebraic approach of the iterative reconstruction algorithm (ART), and on the maximum likelihood estimation method (ML-EM). In addition to that, two subsets of the ART, the simultaneous iterative reconstruction technique (SIRT) and the component averaging algorithms (CAV) have been included to the package employing parallel codes for multiprocessor architecture. All implemented algorithms use two different field functions for the reconstruction of the region. One is traditional voxel function, another is, so called, blob function, smooth spherically symmetric generalized Kaiser-Bessel function. The generation module provides the phantom and projections with background by tracing the prompt gamma-rays for a given scanner geometry. The evaluation module makes statistical comparisons between the generated and reconstructed images, and provides figure-of-merit (FOM) values for the applied reconstruction algorithms. The package has been written in C language and tested under Linux and Windows platforms. The simple graphical user interface (GUI) is used for command execution and visualization purposed. (author)

  10. 1H and 10B NMR and MRI investigation of boron- and gadolinium–boron compounds in boron neutron capture therapy

    International Nuclear Information System (INIS)

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

    2011-01-01

    10 B molecular compounds suitable for Boron Neutron Capture Therapy (BNCT) are tagged with a Gd(III) paramagnetic ion. The newly synthesized molecule, Gd-BPA, is investigated as contrast agent in Magnetic Resonance Imaging (MRI) with the final aim of mapping the boron distribution in tissues. Preliminary Nuclear Magnetic Resonance (NMR) measurements, which include 1 H and 10 B relaxometry in animal tissues, proton relaxivity of the paramagnetic Gd-BPA molecule in water and its absorption in tumoral living cells, are reported.

  11. 1H and 10B NMR and MRI investigation of boron- and gadolinium-boron compounds in boron neutron capture therapy.

    Science.gov (United States)

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

    2011-12-01

    (10)B molecular compounds suitable for Boron Neutron Capture Therapy (BNCT) are tagged with a Gd(III) paramagnetic ion. The newly synthesized molecule, Gd-BPA, is investigated as contrast agent in Magnetic Resonance Imaging (MRI) with the final aim of mapping the boron distribution in tissues. Preliminary Nuclear Magnetic Resonance (NMR) measurements, which include (1)H and (10)B relaxometry in animal tissues, proton relaxivity of the paramagnetic Gd-BPA molecule in water and its absorption in tumoral living cells, are reported. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nievaart, V A; Daquino, G G; Moss, R L [JRC European Commission, PO Box 2, 1755ZG Petten (Netherlands)

    2007-06-15

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

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

    Science.gov (United States)

    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

  14. Workshop on neutron capture therapy

    International Nuclear Information System (INIS)

    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

  15. Workshop on neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fairchild, R.G.; Bond, V.P. (eds.)

    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.

  16. Approach to magnetic neutron capture therapy

    International Nuclear Information System (INIS)

    Kuznetsov, Anatoly A.; Podoynitsyn, Sergey N.; Filippov, Victor I.; Komissarova, Lubov Kh.; Kuznetsov, Oleg A.

    2005-01-01

    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

  17. Chemical processes in neutron capture therapy

    International Nuclear Information System (INIS)

    Brown, B.J.

    1975-01-01

    Research into the radiation chemical effects of neutron capture therapy are described. In the use of neutron capture therapy for the treatment of brain tumours, compounds containing an activatable nuclide are selectively concentrated within tumour tissue and irradiated with neutrons. Target compounds for use in therapy must accumulate selectively in high concentrations in the tumour and must be non toxic to the patient. The most suitable of these are the boron hydrides. Radiation dosages, resulting from neutron capture in normal tissue constituents are tabulated. As part of the program to study the radiation-induced chemical processes undergone by boron target compounds, the radiolytic degredation of boron hydride and phenyl boric acid system was investigated. No direct dependence between the yield of the transient radiolytic species and the concentration of the B-compound was observed. (author)

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

    Directory of Open Access Journals (Sweden)

    Mao Xinggang

    2010-12-01

    Full Text Available Abstract 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 60Co] γ-rays (P P Conclusions Compared with ��-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by

  19. PEMODELAN KOLIMATOR DI RADIAL BEAM PORT REAKTOR KARTINI UNTUK BORON NEUTRON CAPTURE THERAPY

    Directory of Open Access Journals (Sweden)

    Bemby Yulio Vallenry

    2015-03-01

    Full Text Available Salah satu metode terapi kanker adalah Boron Neutron Capture Therapy (BNCT. BNCT memanfaatkan tangkapan neutron oleh 10B yang terendapkan pada sel kanker. Keunggulan BNCT dibandingkan dengan terapi radiasi lainnya adalah tingkat selektivitas yang tinggi karena tingkatannya adalah sel. Pada penelitian ini dilakukan pemodelan kolimator di radial beamport reaktor Kartini sebagai dasar pemilihan material dan manufature kolimator sebagai sumber neutron untuk BNCT. Pemodelan ini dilakukan dengan simulasi menggunakan perangkat lunak Monte Carlo N-Particle versi 5 (MCNP 5. MCNP 5 adalah suatu paket program untuk memodelkan sekaligus menghitung masalah transpor partikel dengan mengikuti sejarah hidup neutron semenjak lahir, bertranspor pada bahan hingga akhirnya hilang karena mengalami reaksi penyerapan atau keluar dari sistem. Pemodelan ini menggunakan variasi material dan ukurannya agar menghasilkan nilai dari tiap parameter-parameter yang sesuai dengan rekomendasi I International Atomic Energy Agency (IAEA untuk BNCT, yaitu fluks neutron epitermal (Фepi > 9 n.cm-2.s-1, rasio antara laju dosis neutron cepat dan fluks neutron epitermal (Ḋf/Фepi 0,7. Berdasarkan hasil optimasi dari pemodelan ini, material dan ukuran penyusun kolimator yang didapatkan yaitu 0,75 cm Ni sebagai dinding kolimator, 22 cm Al sebagai moderator dan 4,5 cm Bi sebagai perisai gamma. Keluaran berkas radiasi yang dihasilkan dari pemodelan kolimator radial beamport yaitu Фepi = 5,25 x 106 n.cm-2s-1, Ḋf/Фepi =1,17 x 10-13 Gy.cm2.n-1, Ḋγ/Фepi = 1,70 x 10-12 Gy.cm2.n-1, Фth/Фepi = 1,51 dan J/Фepi = 0,731. Berdasarkan penelitian ini, hasil optimasi 5 parameter sebagai persyaratan kolimator untuk BNCT yang keluar dari radial beam port tidak sepenuhnya memenuhi kriteria yang direkomendasikan oleh IAEA sehingga perlu dilakukan penelitian lebih lanjut agar tercapainya persyaratan IAEA. Kata kunci: BNCT, radial beamport, MCNP 5, kolimator   One of the cancer therapy methods is

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

    International Nuclear Information System (INIS)

    Lim, Diana; Quah, Daniel SC; Leech, Michelle; Marignol, Laure

    2015-01-01

    This review compares the safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of previously irradiated, inoperable locoregional recurrent HNC patients and compares BNCT against the standard treatment of platinum-based chemotherapy. Our analysis of published clinical trials highlights efficacy of BNCT associated with mild side effects. However, the use of BNCT should be explored in stratified randomised trials. - Highlights: • BNCT can prolong median overall survival. • BNCT can be associated with severe adverse effects. • BNCT may be comparable to chemotherapy-based regimens. • BNCT may be comparable to re-irradiation techniques regimens in patients with low performance status.

  1. Investigation on the neutron beam characteristics for boron neutron capture therapy with 3D and 2D transport calculations

    International Nuclear Information System (INIS)

    Kodeli, I.; Diop, C.M.; Nimal, J.C.

    1994-01-01

    In the framework of future Boron Neutron Capture Therapy (BNCT) experiments, where cells and animals irradiations are planned at the research reactor of Strasbourg University, the feasibility to obtain a suitable epithermal neutron beam is investigated. The neutron fluence and spectra calculations in the reactor are performed using the 3D Monte Carlo code TRIPOLI-3 and the 2D SN code TWODANT. The preliminary analysis of Al 2 O 3 and Al-Al 2 O 3 filters configurations are carried out in an attempt to optimize the flux characteristics in the beam tube facility. 7 figs., 7 refs

  2. Boron neutron capture therapy (BNCT) for glioblastoma multiforme using the epithermal neutron beam at the Brookhaven Medical Research Reactor

    International Nuclear Information System (INIS)

    Capala, J.; Diaz, A.Z.; Chadha, M.

    1997-01-01

    The abstract describes evaluation of boron neutron capture therapy (BNCT) for two groups of glioblastoma multiforme patients. From September 1994 to February 1996 15 patients have been treated. In September 1997 another 34 patients were examined. Authors determined a safe starting dose for BNCT using epithermal neutrons and BPA-F. They have also evaluated adverse effects of BNCT at this starting dose. Therapeutic effectiveness of this starting dose has been evaluated. No significant side effects from BPA-F infusion or BNCT treatment were observed in normal brains

  3. Boron neutron capture therapy (BNCT) for glioblastoma multiforme using the epithermal neutron beam at the Brookhaven Medical Research Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Capala, J. [Brookhaven National Lab., Upton, NY (United States); Diaz, A.Z.; Chadha, M. [Univ. Hospital, State Univ. of New York, NY (United States)] [and others

    1997-12-31

    The abstract describes evaluation of boron neutron capture therapy (BNCT) for two groups of glioblastoma multiforme patients. From September 1994 to February 1996 15 patients have been treated. In September 1997 another 34 patients were examined. Authors determined a safe starting dose for BNCT using epithermal neutrons and BPA-F. They have also evaluated adverse effects of BNCT at this starting dose. Therapeutic effectiveness of this starting dose has been evaluated. No significant side effects from BPA-F infusion or BNCT treatment were observed in normal brains.

  4. Measurement of in-phantom neutron flux and gamma dose in Tehran research reactor boron neutron capture therapy beam line.

    Science.gov (United States)

    Bavarnegin, Elham; Sadremomtaz, Alireza; Khalafi, Hossein; Kasesaz, Yaser

    2016-01-01

    Determination of in-phantom quality factors of Tehran research reactor (TRR) boron neutron capture therapy (BNCT) beam. The doses from thermal neutron reactions with 14N and 10B are calculated by kinetic energy released per unit mass approach, after measuring thermal neutron flux using neutron activation technique. Gamma dose is measured using TLD-700 dosimeter. Different dose components have been measured in a head phantom which has been designed and constructed for BNCT purpose in TRR. Different in-phantom beam quality factors have also been determined. This study demonstrates that the TRR BNCT beam line has potential for treatment of superficial tumors.

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

    International Nuclear Information System (INIS)

    Wallace, Christine

    2001-01-01

    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 FR-om 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

  6. ESR-dosimetry in thermal and epithermal neutron fields for application in boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, Tobias

    2016-01-22

    Dosimetry is essential for every form of radiotherapy. In Boron Neutron Capture Therapy (BNCT) mixed neutron and gamma fields have to be considered. Dose is deposited in different neutron interactions with elements in the penetrated tissue and by gamma particles, which are always part of a neutron field. The therapeutic dose in BNCT is deposited by densely ionising particles, originating from the fragmentation of the isotope boron-10 after capture of a thermal neutron. Despite being investigated for decades, dosimetry in neutron beams or fields for BNCT remains complex, due to the variety in type and energy of the secondary particles. Today usually ionisation chambers combined with metal foils are used. The applied techniques require extensive effort and are time consuming, while the resulting uncertainties remain high. Consequently, the investigation of more effective techniques or alternative dosimeters is an important field of research. In this work the possibilities of ESR-dosimeters in those fields have been investigated. Certain materials, such as alanine, generate stable radicals upon irradiation. Using Electron Spin Resonance (ESR) spectrometry the amount of radicals, which is proportional to absorbed dose, can be quantified. Different ESR detector materials have been irradiated in the thermal neutron field of the research reactor TRIGA research reactor in Mainz, Germany, with five setups, generating different secondary particle spectra. Further irradiations have been conducted in two epithermal neutron beams. The detector response, however, strongly depends on the dose depositing particle type and energy. It is hence necessary to accompany measurements by computational modelling and simulation. In this work the Monte Carlo code FLUKA was used to calculate absorbed doses and dose components. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using amorphous track models. For the simulation, detailed models of

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

    Science.gov (United States)

    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.

  8. Iodine neutron capture therapy

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    Wang, Peng; Zhen, Haining; Jiang, Xinbiao; Zhang, Wei; Cheng, Xin; Guo, Geng; Mao, Xinggang; Zhang, Xiang

    2010-01-01

    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. The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [ 60 Co] 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 [ 60 Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [ 60 Co] γ-rays; Group C included cells treated with 8 Gy of [ 60 Co] 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. Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [ 60 Co] 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 treated with

  10. A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Boron containing magnetic nanoparticles for neutron capture therapy – an innovative approach for specifically targeting tumors

    International Nuclear Information System (INIS)

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

    2015-01-01

    The selective delivery of 10 B into the tumor tissue remains to be further improved for successful and reliable Boron Neutron Capture Therapy applications. Magnetic Drug Targeting using intraarterially administered superparamagnetic nanoparticles and external magnetic fields already exhibited convincing results in terms of highly efficient and selective drug deposition. Using the same technique for the targeted 10 B delivery is a promising new approach. Here, systematic irradiation experiments of phantom cubes containing different concentrations of boron and nanoparticles as well as varying three-dimensional arrangements have been performed. - Highlights: • Magnetic Drug Targeting is a possible approach to substantially improve BNCT. • SPIONs did not influence the radiation dose deposition. • Superior dose deposition in gel phantoms reflecting Magnetic Drug Targeting set up.

  12. 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.

    Science.gov (United States)

    Ciofani, Gianni; Raffa, Vittoria; Menciassi, Arianna; Cuschieri, Alfred

    2008-11-25

    Boron neutron capture therapy (BNCT) is increasingly being used in the treatment of several aggressive cancers, including cerebral glioblastoma multiforme. The main requirement for this therapy is selective targeting of tumor cells by sufficient quantities of (10)B 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.

  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

    Directory of Open Access Journals (Sweden)

    Ciofani Gianni

    2008-01-01

    Full Text Available Abstract 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.

  14. Investigation of current status in Europe and USA on boron neutron capture therapy

    International Nuclear Information System (INIS)

    2000-11-01

    This report describes on the spot investigation results of current status of medical irradiation in Europe and USA at Feb. 1999. In HFR (Netherlands), the phase 1 study with the Joint Research Centre (JRC) of the EU had been already finished in those days, at the same time, an improvement of medical irradiation field of VTT(Finland) had been finishing and then clinical trial research had been about to start. On the other hand, phase 1 studies by two groups of BNL (Brook heaven National Laboratory) and MIT (Nuclear Engineering of Massachusetts Institute of Technology) in US were now in almost final stage, and they would start on phase 2 study. Either reactors of MIT and BNL were in modification to increase neutron flux, especially that employing fission converter into the irradiation facility and installation of irradiation room were carrying out in the former. In Europe and USA, the accelerator-based BNCT planes are now in progress vigorously, and will have reality. A reform of dynamitron accelerator at University of Birmingham was progressed, and the clinical treatment would be started from September 2000. The accelerator group at MIT has a small type of tandem accelerator, and they were performing basic experiment for BNCS (Boron Neutron Capture Synovectomy) with this accelerator. The concept design for an accelerator and a moderator had been finished at Lawrence Berkeley National Laboratory and University of Berkeley. (author)

  15. Design of polymeric carrier containing boron for boron neutron capture therapy and its use in tissue cultures

    International Nuclear Information System (INIS)

    Kahraman, G.

    2004-01-01

    The aim of this study is the synthesis of a new alternative boron containing polymer carrier to be used for Boron Neutron Capture Therapy (BNCT) (one of the treatment methods for brain tumours) and to investigate its use in cell cultures. First of all, B-containing copolymer were synthesized by complex-radical copolymerization of vinylphenylboronic acid and maleic anhydride with 2, 2- azobisisobutyronitrile as an initiator in DMF solvent at 65 degree Celsius under nitrogen atmosphere. Macro branched derivatives of these polymers were synthesized by the partial grafting with α-hydroxy,ω -methoxy-poly(ethylene oxide). Characterization of Poly(VPBA-co-MA) and these macro branched copolymers were performed by FTIR, 1 H NMR spectroscopy, X-Ray diffraction, DSC and TGA analyses. As a result of these analyses, it was observed that these macro branched copolymers had a higher crystallinity and thermal stability than the copolymer. These properties of macro branched copolymers are explained by self-organized H-bonding effect in radical copolymerization and grafting reactions and by the formation of self assembled supramolecular architecture. The selected macro branched copolymer was incorporated by poly(ethylene imine) in order to uptake to cell and thus, this synthesized macro complex copolymer [(VFBA-co-MA)-g-PEG/PEI] was charged with positive charge. As a result of FTIR analysis, it was observed that COO - .NH + complex was formed. After the cell culture experiment, it was observed that this macro complex copolymer labelled with fluorescein up took to HeLa cells with 7 % efficiency. And then, folic acid was incorporated in [(VFBA-co-MA)-g-PEG/PEI] macro complex in order to provide selective targeting properties with tumour cells. As a result of the experiment of cell culture containing mixture of HeLa and fibroblast cell, it was observed that [(VFBA-co-MA)-g-PEG/PEI]-FA macro complex went towards to HeLa cells selectively by means of fluorescence microscopy. Poly

  16. Accelerators and neutron capture therapy

    International Nuclear Information System (INIS)

    Burlon, A. A.; Kreiner, A. J.; Valda, A.

    2002-01-01

    Within the frame of Accelerator Based Boron Neutron Capture Therapy (AB-BNCT), the 7Li(p,n)7Be reaction, relatively near its energy threshold is one of the most promising, due to its high yield and low neutron energy. In this work a thick LiF target irradiated with a proton beam was studied as a neutron source. The 1.88-2.0 MeV proton beam was produced by the tandem accelerator TANDAR at CNEA's facilities in Buenos Aires. A water-filled phantom, containing a boron sample was irradiated with the resulting neutron flux. The 10B(n,αγ)7Li boron neutron capture reaction produces a 0.478 MeV gamma ray in 94% of the cases. The neutron yield was measured through the detection of this gamma ray using a hyperpure germanium detector with an anti-Compton shield. In addition, the thermal neutron flux was evaluated at different depths inside the phantom using bare and Cd-covered gold foils. A maximum neutron thermal flux of 1.4x108 cm-2s-1mA-1 was obtained at 4.2 cm from the phantom surface. In order to optimize the design of the neutron production target and the beam shaping assembly extensive Monte Carlo Neutron and Photon (MCNP) simulations have been performed. Neutron fields from a thick LiF and a Li metal target (with both a D2O-graphite and a Al/AlF3-graphite moderator/reflector assembly) were evaluated along the centerline of a head and a whole body phantom. Simulations were carried out for 1.89, 2.0 and 2.3 MeV proton beams. The results show that it is more advantageous to irradiate the target with 2.3 MeV near-resonance protons, instead of very near threshold, because of the higher neutron yield at this energy. On the other hand, the Al/AlF3-graphite exhibits a more efficient performance than D2O in terms of tumor to maximum healthy tissue dose ratio. Treatment times of less than 15 min and tumor control probabilities larger than 98% are obtained for a 50 mA, 2.3 MeV proton beam. The alternative neutron-producing reaction 13C(d,n) is also briefly reviewed. A proposal

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Synthesis of o-carboranylmethyl ethers of steroids as potential target substrates for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Schneiderova, L.; Gruener, B.; Strouf, O.; Kimlova, I.

    1992-01-01

    o-carboranylmethyl ethers of steroids were synthesized by insertion of steroidal 2-propynyloxy derivatives into 6,9-bis(acetonitrile)decarborane. This reaction provided compounds with an estrane and androstane skeleton, potentially useful in boron neutron capture therapy of hormone-sensitive forms of cancer: 17β-o-carboranylmethyl ether of estradiol IXb (yield 14%) and 3β- and 17β-carboranylmethyl ethers of androstenediol Vb and VIIb (yield 12% and 13%, respectively). Jones oxidation gave the carboranyl derivative of androsten-17-one VIb in 75% yield. As shown by a study of insertion of 3β-(2-propynyloxy)cholest-5-ene (IVa), the low yields of the insertion reaction cannot be increased by change in the reaction conditions. The relative binding affinity of compound IXb to the estrogen receptor from rat uterine and human breast tumor cytosol was 3.0 and 0.29%, respectively, of that of estradiol. (author) 2 figs., 2 tabs., 20 refs

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

    Energy Technology Data Exchange (ETDEWEB)

    Thatar Vento, V., E-mail: Vladimir.ThatarVento@gmail.com [Gerencia de Investigacion y Aplicaciones, CNEA, Av. Gral. Paz 1499 (1650), San Martin, Buenos Aires (Argentina)] [CONICET, Av. Rivadavia 1917 (1033), Ciudad Autonoma de Buenos Aires (Argentina); Bergueiro, J.; Cartelli, D. [Gerencia de Investigacion y Aplicaciones, CNEA, Av. Gral. Paz 1499 (1650), San Martin, Buenos Aires (Argentina)] [CONICET, Av. Rivadavia 1917 (1033), Ciudad Autonoma de Buenos Aires (Argentina); Valda, A.A. [Gerencia de Investigacion y Aplicaciones, CNEA, Av. Gral. Paz 1499 (1650), San Martin, Buenos Aires (Argentina)] [Escuela de Ciencia y Tecnologia, UNSAM, M. Irigoyen 3100 (1650), San Martin, Buenos Aires (Argentina); Kreiner, A.J. [Gerencia de Investigacion y Aplicaciones, CNEA, Av. Gral. Paz 1499 (1650), San Martin, Buenos Aires (Argentina)] [CONICET, Av. Rivadavia 1917 (1033), Ciudad Autonoma de Buenos Aires (Argentina)] [Escuela de Ciencia y Tecnologia, UNSAM, M. Irigoyen 3100 (1650), San Martin, Buenos Aires (Argentina)

    2011-12-15

    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.

  20. Considerations for boron neutron capture therapy studies; Consideracoes sobre o estudo da BNCT (terapia de captura neutronica por boro)

    Energy Technology Data Exchange (ETDEWEB)

    Faria Gaspar, P. de

    1994-12-31

    Radiotherapy is indispensable as a mean to eradicate deeply or infiltrating tumor tissue that can not be removed surgically. Therefore, it is not selective and may also kill the surrounding health tissue. The principle of BNCT (Boron Neutron Capture Therapy) consist in targeting a tumor selectively with a boron-10 compound. This nuclide has a large capture cross section for thermal neutrons and the nuclear reaction and the delivered energy in locus will selective the tumor. Since its initial proposal in 1963 BNCT has made much progress, however it is not used in a routine treatment. In this work it was approached some complex procedures, as the obtention of selective boron compounds, the adequate set up of neutron beams, the biodistribution, the in vivo and in vitro studies, and also human patients treatments. This work provide fundamentals about BNCT to professional of different areas of knowledge since it comprises multidisciplinary study. It includes appendixes for the ones not related to the field for a better comprehension of the many aspects involved. It is also presented a glossary containing technical and basic aspects involved. It is also presented a glossary containing technical and basic terms referred in the work. (author). 174 refs, 1 fig, 12 apps.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-06-06

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

  2. Development of a tri dimensional Monte Carlo code for the study of the microdosimetry in boron neutron capture therapy

    International Nuclear Information System (INIS)

    Santa Cruz, G.A.

    1998-01-01

    Full text: A charged particles transport Monte Carlo code, specially designed for the boron neutron capture therapy microdosimetry study was developed. The code allows the use of real tri dimensional problem geometry, using serial microscopy slides from a biological substrate where the 10 B(n, Alpha) 7 Li, 14 N(n,p) 14 C reactions and events can occur. The spatial distribution of sources ( 10 B, 14 N concentrations), regions of interest (where the energy deposition, linear energy transfer and other parameters will be calculated) and other zones (without boron) are obtained from the images. The code is in the benchmarking stage, using geometrically simple cases and experimental data obtained from microdosimetric spectra from TEPC (Tissue Equivalent Proportional Counters) doped with 10 B. It allows to obtain LET spectra discriminated by event classes, chord-length distributions, dose and frequency mean values and visualizations of the spatial energy deposition. A similar version of the code uses bidimensional images from a tissue sample containing a great number of cellular structures. An equivalence between the microdosimetry of a bidimensional case and a tri dimensional one can be done. If the real distribution of 10 B is known, for example by high resolution alpha-track autoradiography, the code can use this information explicitly. (author) [es

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

    Science.gov (United States)

    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.

  4. Monitoring of blood-10B concentration for boron neutron capture therapy using prompt gamma-ray analysis

    International Nuclear Information System (INIS)

    Raaijmakers, C.P.J.; Konijnenberg, M.W.; Dewit, L.; Mijnheer, B.J.; Haritz, D.; Huiskamp, R.; Philipp, K.; Siefert, A.; Stecher-Rasmussen, F.

    1995-01-01

    The aim of the present study was to monitor the blood- 10 B concentration of laboratory dogs receiving boron neutron capture therapy, in order to obtain optimal agreement between prescribed and actual dose. A prompt gamma-ray analysis system was developed for this purpose at the High Flux Reactor in Petten. The technique was compared with inductively coupled plasma-atomic emission spectrometry and showed good agreement. A substantial variation in 10 B clearance pattern after administration of borocaptate sodium was found between the different dogs. Consequently, the irradiation commencement was adjusted to the individually determined boron elimination curve. Mean blood- 10 B concentratios during irradiation of 25.8±2.2 μg/g (1 SD, n=18) and 49.3±5.3 μg/g (1 SD, n=17) were obtained for intended concentrations of 25 μg/g and 50 μg/g, respectively. These variations are a factor of two smaller than irradiations performed at a uniform post-infusion irradiation starting time. Such a careful bolld- 10 B monitoring procedure is a prerequisite for accurately obtaining such steep dose-response curves as observed during the dog study. (orig.)

  5. PBF/BNCT [power burst facility/boron neutron capture therapy] program for cancer treatment

    International Nuclear Information System (INIS)

    Dorn, R.V. III.

    1989-06-01

    Highlights of the PBF/BNCT Program during June include progress within the areas of gross boron analysis in tissue, blood, and urine; analytical methodologies development for BSH (sodium borocaptate) purity determination; boron microscopic (subcellular) analytical development; noninvasive boron quantification determination; dosimetry; and analytical radiation transport and interaction modeling for BNCT

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

    Directory of Open Access Journals (Sweden)

    Barth Rolf F

    2012-08-01

    Full Text Available Abstract 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

  7. Boronated Unnatural Cyclic Amino Acids as Potential Delivery Agents for Neutron Capture Therapy

    Science.gov (United States)

    Kabalka, George W.; Shaikh, Aarif L.; Barth, Rolf F.; Huo, Tianyao; Yang, Weilian; Gordnier, Pamela M.; Chandra, Subhash

    2011-01-01

    Boron delivery characteristics of cis and trans isomers of a boronated unnatural amino acid, 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC) were tested in B16 mouse model for human melanoma. Both ABCPC isomers delivered comparable boron to B16 melanoma tumor cells as L-p-boronophenylalanine (BPA). Secondary ion mass spectrometry (SIMS) analysis revealed the presence of boron throughout the tumor from these compounds, and a near homogeneous distribution between the nucleus and cytoplasm of B16 cells grown in vitro. These encouraging observations support further studies of these new boron carriers in BNCT. PMID:21481596

  8. Neutron spectrum for neutron capture therapy in boron; Espectro de neutrones para terapia por captura de neutrones en boro

    Energy Technology Data Exchange (ETDEWEB)

    Medina C, D.; Soto B, T. G. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Programa de Doctorado en Ciencias Basicas, 98068 Zacatecas, Zac. (Mexico); Baltazar R, A. [Universidad Autonoma de Zacatecas, Unidad Academica de Ingenieria Electrica, Programa de Doctorado en Ingenieria y Tecnologia Aplicada, 98068 Zacatecas, Zac. (Mexico); Vega C, H. R., E-mail: dmedina_c@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas, Zac. (Mexico)

    2016-10-15

    Glioblastoma multiforme is the most common and aggressive of brain tumors and is difficult to treat by surgery, chemotherapy or conventional radiation therapy. One treatment alternative is the Neutron Capture Therapy in Boron, which requires a beam modulated in neutron energy and a drug with {sup 10}B able to be fixed in the tumor. When the patients head is exposed to the neutron beam, they are captured by the {sup 10}B and produce a nucleus of {sup 7}Li and an alpha particle whose energy is deposited in the cancer cells causing it to be destroyed without damaging the normal tissue. One of the problems associated with this therapy is to have an epithermal neutrons flux of the order of 10{sup 9} n/cm{sup 2}-sec, whereby irradiation channels of a nuclear research reactor are used. In this work using Monte Carlo methods, the neutron spectra obtained in the radial irradiation channel of the TRIGA Mark III reactor are calculated when inserting filters whose position and thickness have been modified. From the arrangements studied, we found that the Fe-Cd-Al-Cd polyethylene filter yielded a ratio between thermal and epithermal neutron fluxes of 0.006 that exceeded the recommended value (<0.05), and the dose due to the capture gamma rays is lower than the dose obtained with the other arrangements studied. (Author)

  9. Neutron capture therapy at Brookhaven National Laboratory

    International Nuclear Information System (INIS)

    Fairchild, R.G.; Slatkin, D.N.; Gabel, D.

    1986-01-01

    Application of the 10 B(n,α) 7 Li reaction to cancer radiotherapy (Neutron Capture therapy, or NCT) has intrigued investigators since shortly after the discovery of the neutron. This paper summarizes data describing recently developed boronated compounds designed to serve as vehicles for boron transport to tumor. Whole-body (mouse) Neutron Capture Radiograms (NCR) of some of the most promising compounds are presented; these graphically demonstrate selective uptake in tumor, at times varying from hours to days post administration. Comparison is made to the ubiquitous distribution of inorganic boron compounds used in the first clinical trials of NCT. Since some compounds are now available that allow physiological targeting of boron to tumor at concentrations adequate for therapy, the NCR technique can be used to evaluate important questions concerning the microdistribution of boron within the tumor. The implication of these compounds to NCT is evaluated in terms of Therapeutic Gain (TG). The optimization of NCT by using band-pass filtered neutron beams is described, again in terms of TG, and irradiation times with these less intense beams are estimated. 35 references, 12 figures, 4 tables

  10. Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models

    Directory of Open Access Journals (Sweden)

    Charles A Maitz

    2017-08-01

    Full Text Available Boron neutron capture therapy (BNCT was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. Mice were implanted with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH3(CH215–7,8-C2B9H11] in the lipid bilayer and encapsulated Na3[1-(2`-B10H9-2-NH3B10H8] within the liposomal core. Mice were irradiated 30 hours after the second injection in a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. Despite relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.

  11. Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

    Science.gov (United States)

    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.

  12. Antibodies and antiestrogens combined with boron for use in the neutron capture therapy

    International Nuclear Information System (INIS)

    Abraham, R.

    1987-01-01

    The ZR-75-1 cell line developed from a mammary carcinoma was chosen to characterise the binding of antiestrogen U23.469-M to the cell, which was subsequently compared to that of a derivative combined with boron. It was found that the original U23.469-M showed antiestrogenic activity, while this effect was largely abolished after the substance had been modified using b-decachloro-o-carborane. In this study, boron-conjugated antibodies were produced in order to find out whether those modified immunoglobulins would be suitable to bind sufficient quantities of boron to the tumour cells. It was calculated by experts on radiation biology that a minimum of 1000 boron atoms is required for a tumour-specific antibody to be therapeutically effective. When oxidated dextran of a molecular weight of 33 kD was used as a linking molecule, a reproducible method could be developed that permitted more than 1000 boron atoms to be bound per antibody. In one of the monoclonal antibodies tested here a combination with boron could, however, only be achieved at the expense of complete inactivation. A model was developed allowing to significantly increase the number modified antibodies attached to any one tumour cell. The cell binding experiments and radioimmunoassays then carried out were able to show that the number of antibodies bound to tumour cells can be increased to different degrees, depending on the monoclonal antibody used in each case. (orig./MG) [de

  13. T2 corrected quantification method of L-p-boronophenylalanine using proton magnetic resonance spectroscopy for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Yamamoto, Yohei; Isobe, Tomonori; Yamamoto, Tetsuya; Shibata, Yasushi; Anno, Izumi; Nakai, Kei; Shirakawa, Makoto; Matsushita, Akira; Sato, Eisuke; Matsumura, Akira

    2009-01-01

    In the present study, we aimed to evaluate a T2 corrected quantification method of L-p-boronophenylalanine (BPA) concentration using proton magnetic resonance spectroscopy (MRS). We used five phantoms containing BPA (1.5, 3.0, 5.0, 7.5, and 10 mmol/kg=15, 30, 50, 75, and 100 μg 10 B/g), N-acetyl-aspartic acid (NAA: 3.0 mmol/kg), creatine (Cr: 5.0 mmol/kg), and choline (Cho: 3.0 mmol/kg). The signal intensities of BPA and internal water were corrected by T2 relaxation time. The absolute concentrations of BPA were calculated by proton MRS using an internal water signal as a standard. The major BPA peaks were detected between 7.1 and 7.6 ppm. Mean T2 relaxation time was 314.3±10.8 ms in BPA, 885.1±39.7 ms in internal water. The calculated BPA concentrations were almost same as the actual concentration of BPA and the correlation coefficient was 0.99. Our BPA quantification method was very simple and non-invasive, also it had high accuracy. Therefore, our results indicate that proton MRS can be potentially useful technique for in vivo BPA quantification in boron neutron capture therapy (BNCT).

  14. Boron neutron capture therapy design calculation of a 3H(p,n reaction based BSA for brain cancer setup

    Directory of Open Access Journals (Sweden)

    Bassem Elshahat

    2015-09-01

    Full Text Available Purpose: Boron neutron capture therapy (BNCT is a promising technique for the treatment of malignant disease targeting organs of the human body. Monte Carlo simulations were carried out to calculate optimum design parameters of an accelerator based beam shaping assembly (BSA for BNCT of brain cancer setup.Methods: Epithermal beam of neutrons were obtained through moderation of fast neutrons from 3H(p,n reaction in a high density polyethylene moderator and a graphite reflector. The dimensions of the moderator and the reflector were optimized through optimization of epithermal / fast neutron intensity ratio as a function of geometric parameters of the setup. Results: The results of our calculation showed the capability of our setup to treat the tumor within 4 cm of the head surface. The calculated peak therapeutic ratio for the setup was found to be 2.15. Conclusion: With further improvement in the polyethylene moderator design and brain phantom irradiation arrangement, the setup capabilities can be improved to reach further deep-seated tumor.

  15. Stability of high-speed lithium sheet jets for the neutron source in Boron Neutron Capture Therapy (BNCT)

    International Nuclear Information System (INIS)

    Nakagawa, Masamichi; Takahashi, Minoru; Aritomi, Masanori; Kobayashi, Toru

    2014-01-01

    The stability of high-speed liquid lithium sheet jets was analytically studied for the neutron source in Boron Neutron Capture Therapy (BNCT), which makes cancers and tumors curable with cell-level selections and hence high QOL. The object of our research is to realize the thin and high-speed plane sheet jets of liquid lithium in a high-vacuum as an accelerator target. Linear analysis approach is made to the stability on thin plane sheet jets of liquid lithium in a high-vacuum, and then our analytical results were compared with the previous experimental ones. We proved that the waves of surface tension on thin lithium sheet jets in a high-vacuum are of supercritical flows and neutral stable under about 17.4 m/s in flow velocity and that the fast non-dispersive anti-symmetric waves are more significant than the very slow dispersive symmetric waves. We also formulated the equation of shrinking angle in isosceles-triangularly or isosceles-trapezoidal shrinking sheet jets corresponding to the Mach angle of supersonic gas flows. This formula states universally the physical meaning of Weber number of sheet jets on the wave of surface tension in supercritical flows. We obtained satisfactory prospects (making choice of larger flow velocity U and larger thickness of sheet a) to materialize a liquid target of accelerator in BNCT. (author)

  16. An accelerator-based Boron Neutron Capture Therapy (BNCT) facility based on the 7Li(p,n)7Be

    Science.gov (United States)

    Musacchio González, Elizabeth; Martín Hernández, Guido

    2017-09-01

    BNCT (Boron Neutron Capture Therapy) is a therapeutic modality used to irradiate tumors cells previously loaded with the stable isotope 10B, with thermal or epithermal neutrons. This technique is capable of delivering a high dose to the tumor cells while the healthy surrounding tissue receive a much lower dose depending on the 10B biodistribution. In this study, therapeutic gain and tumor dose per target power, as parameters to evaluate the treatment quality, were calculated. The common neutron-producing reaction 7Li(p,n)7Be for accelerator-based BNCT, having a reaction threshold of 1880.4 keV, was considered as the primary source of neutrons. Energies near the reaction threshold for deep-seated brain tumors were employed. These calculations were performed with the Monte Carlo N-Particle (MCNP) code. A simple but effective beam shaping assembly (BSA) was calculated producing a high therapeutic gain compared to previously proposed facilities with the same nuclear reaction.

  17. User's manual of a supporting system for treatment planning in boron neutron capture therapy. JAERI computational dosimetry system

    International Nuclear Information System (INIS)

    Kumada, Hiroaki; Torii, Yoshiya

    2002-09-01

    A boron neutron capture therapy (BNCT) with epithermal neutron beam is expected to treat effectively for malignant tumor that is located deeply in the brain. It is indispensable to estimate preliminarily the irradiation dose in the brain of a patient in order to perform the epithermal neutron beam BNCT. Thus, the JAERI Computational Dosimetry System (JCDS), which can calculate the dose distributions in the brain, has been developed. JCDS is a software that creates a 3-dimensional head model of a patient by using CT and MRI images and that generates a input data file automatically for calculation neutron flux and gamma-ray dose distribution in the brain by the Monte Carlo code: MCNP, and that displays the dose distribution on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By treating CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is able to be made easily. The three-dimensional head image is editable to simulate the state of a head after its surgical processes such as skin flap opening and bone removal for the BNCT with craniotomy that are being performed in Japan. JCDS can provide information for the Patient Setting System to set the patient in an actual irradiation position swiftly and accurately. This report describes basic design and procedure of dosimetry, operation manual, data and library structure for JCDS (ver.1.0). (author)

  18. User's manual of a supporting system for treatment planning in boron neutron capture therapy. JAERI computational dosimetry system

    CERN Document Server

    Kumada, H

    2002-01-01

    A boron neutron capture therapy (BNCT) with epithermal neutron beam is expected to treat effectively for malignant tumor that is located deeply in the brain. It is indispensable to estimate preliminarily the irradiation dose in the brain of a patient in order to perform the epithermal neutron beam BNCT. Thus, the JAERI Computational Dosimetry System (JCDS), which can calculate the dose distributions in the brain, has been developed. JCDS is a software that creates a 3-dimensional head model of a patient by using CT and MRI images and that generates a input data file automatically for calculation neutron flux and gamma-ray dose distribution in the brain by the Monte Carlo code: MCNP, and that displays the dose distribution on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By treating CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is able to be made easily. The three-dimensional head image is editable to ...

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

    International Nuclear Information System (INIS)

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

    1997-01-01

    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 endash 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. copyright 1997 American Institute of Physics

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

    International Nuclear Information System (INIS)

    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 x 10 8 n/cm 2 · s. The fast neutron and gamma radiation KERMA factors are 10 x 10 -11 cGy·cm 2 /n epi and 20 x 10 -11 cGy·cm 2 /n 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

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

    Science.gov (United States)

    Brandão, S F; Campos, T P R

    2015-07-01

    This article proposes a combination of californium-252 ((252)Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Dosimetric evaluations were performed on three protocol set-ups: (252)Cf 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). 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. Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the (252)Cf source, sparing the normal brain tissue. 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.

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

    Science.gov (United States)

    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

  3. In vitro induction of chromosomal aberrations in human lymphocytes, with and without boron 10, by radiations concerned in boron neutron capture therapy.

    Science.gov (United States)

    Lloyd, D C; Edwards, A A; Prosser, J S; Finnon, P; Moquet, J E

    1988-12-01

    A beam consisting of mainly 24 keV neutrons has been constructed for radiobiological studies to evaluate the potential of these particles for treating deep tumours by the boron capture reaction. The induction of chromosomal aberrations in human lymphocytes in vitro was examined and a linear dose effect with a relative biological effectiveness similar to fission neutrons was obtained. For samples placed at depths in a plastic phantom the aberration yields declined with depth at a rate matching the fall in the sum of dose due to proton recoils and neutron capture in nitrogen 14. The presence of boron 10 at 30 micrograms ml-1 did not affect the aberration yield. By using the mixed sample method, the probability of interphase death or mitotic delay in cells crossed by an alpha particle or lithium-7 ion produced in the boron capture reaction was shown to be close to 1.0. Thus these cells are prevented from coming to mitosis in culture. The implications for boron capture therapy are that this filtered beam has a "high LET" effect which could lead to poor normal tissue sparing. However there may be a significant therapeutic advantage due to a high probability of killing tumour cells that have incorporated boron 10.

  4. Radioprotective agents to reduce BNCT (Boron Neutron Capture Therapy) induced mucositis in the hamster cheek pouch

    International Nuclear Information System (INIS)

    Monti Hughes, A.; Pozzi, E.C.C.; Thorp, S.

    2013-01-01

    Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of BNCT mediated by boronophenylalanine (BPA) in the hamster cheek pouch oral cancer and pre cancer model. Despite therapeutic efficacy, mucositis induced in premalignant tissue was dose limiting and favored, in some cases, tumor development. In a clinical scenario, oral mucositis limits the dose administered to head and neck tumors. Aim: Our aim was to evaluate the effect of the administration of different radioprotective agents, seeking to reduce BNCT-induced mucositis to acceptable levels in dose-limiting premalignant tissue; without compromising therapeutic effect evaluated as inhibition on tumor development in premalignant tissue; without systemic or local side effects; and without negative effects on the biodistribution of the boron compound used for treatment. Materials and methods: Cancerized hamsters with DMBA (dimethylbenzanthracene) were treated with BPA-BNCT 5 Gy total absorbed dose to premalignant tissue, at the RA-3 Nuclear Reactor, divided into different groups: 1-treated with FLUNIXIN; 2- ATORVASTATIN; 3-THALIDOMIDE; 4-HISTAMINE (two concentrations: Low -1 mg/ml- and High -5 mg/ml-); 5-JNJ7777120; 6-JNJ10191584; 7-SALINE (vehicle). Cancerized animals without any treatment (neither BNCT nor radioprotective therapy) were also analyzed. We followed the animals during one month and evaluated the percentage of animals with unacceptable/severe mucositis, clinical status and percentage of animals with new tumors post treatment. We also performed a preliminary biodistribution study of BPA + Histamine “low” concentration to evaluate the potential effect of the radioprotector on BPA biodistribution. Results: Histamine

  5. Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

    International Nuclear Information System (INIS)

    Coderre, J.A.; Chanana, A.D.; Joel, D.D.; Liu, H.B.; Slatkin, D.N.; Wielopolski, L.; Bergland, R.; Elowitz, E.; Chadha, M.

    1994-01-01

    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

  6. Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Coderre, J.A.; Chanana, A.D.; Joel, D.D.; Liu, H.B.; Slatkin, D.N.; Wielopolski, L. [Brookhaven National Lab., Upton, NY (United States); Bergland, R.; Elowitz, E. [Beth Israel Medical Center, New York, NY (United States). Dept. of Neurosurgery; Chadha, M. [Beth Israel Medical Center, New York, NY (United States). Dept. of Radiation Oncology

    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.

  7. Dosimetric comparative analysis between 10 MV Megavoltage unidirectional beam and boron neutron capture therapy for brain tumors treatment

    International Nuclear Information System (INIS)

    Brandao, Samia F.; Campos, Tarcisio P.R.

    2011-01-01

    This paper present a comparative dosimetric analysis between boron neutron capture therapy and 10 MV megavoltage employed in brain tumor treatments, limited to a unidirectional beam. A computational phantom of a human head was developed to be used in computational simulations of the two protocols, conducted in MCNP5 code. This phantom represents several head's structures, mainly, the central nervous system and a tumor that represents a Glioblastoma Multiform - one of the most malignant and aggressive brain tumors. Absorbed and biological weighted dose rates and neutron fluency in the computational phantom were evaluated from the MCNP5 code. The biologically weighted dose rate to 10 MV megavoltage beam presented no specificity in deposited dose in tumor. The average total biologically weighted dose rate in tumor was 9.93E-04 RBE.Gy.h -1 /Mp.s -1 while in healthy tissue it was 8.67E-04 RBE.Gy.h -1 /Mp.s - 1. On the BNCT simulations the boron concentration was particularly relevant since the largest dose deposition happened in borate tissues. The average total biologically weighted dose rate in tumor was 3.66E-02 RBE.Gy.h -1 /Mp.s -1 while in healthy tissue it was 1.39E-03 RBE.Gy.h -1 /Mp.s -1 . In comparison to the 10 MV megavoltage beam, BNCT showed clearly a largest dose deposition in the tumor, on average, 37 times larger than in the megavoltage beam, while in healthy tissue that average was only 1,6 time larger in BNCT. (author)

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

    Science.gov (United States)

    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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Comparison of the radiobiological effects of Boron neutron capture therapy (BNCT) and conventional Gamma Radiation

    International Nuclear Information System (INIS)

    Dagrosa, Maria A.; Carpano, Marina; Perona, Marina; Thomasz, Lisa; Juvenal, Guillermo J.; Pisarev, Mario; Pozzi, Emiliano; Thorp, Silvia

    2009-01-01

    BNCT is an experimental radiotherapeutic modality that uses the capacity of the isotope 10 B to capture thermal neutrons leading to the production of 4 He and 7 Li, particles with high linear energy transfer (LET). The aim was to evaluate and compare in vitro the mechanisms of response to the radiation arising of BNCT and conventional gamma therapy. We measured the survival cell fraction as a function of the total physical dose and analyzed the expression of p27/Kip1 and p53 by Western blotting in cells of colon cancer (ARO81-1). Exponentially growing cells were distributed into the following groups: 1) BPA (10 ppm 10 B) + neutrons; 2) BOPP (10 ppm 10 B) + neutrons; 3) neutrons alone; 4) gamma-rays. A control group without irradiation for each treatment was added. The cells were irradiated in the thermal neutron beam of the RA-3 (flux= 7.5 10 9 n/cm 2 sec) or with 60 Co (1Gy/min) during different times in order to obtain total physical dose between 1-5 Gy (±10 %). A decrease in the survival fraction as a function of the physical dose was observed for all the treatments. We also observed that neutrons and neutrons + BOPP did not differ significantly and that BPA was the more effective compound. Protein extracts of irradiated cells (3Gy) were isolated to 24 h and 48 h post radiation exposure. The irradiation with neutrons in presence of 10 BPA or 10 BOPP produced an increase of p53 at 24 h maintain until 48 h. On the contrary, in the groups irradiated with neutrons alone or gamma the peak was observed at 48 hr. The level of expression of p27/Kip1 showed a reduction of this protein in all the groups irradiated with neutrons (neutrons alone or neutrons plus boron compound), being more marked at 24 h. These preliminary results suggest different radiobiological response for high and low let radiation. Future studies will permit establish the role of cell cycle in the tumor radio sensibility to BNCT. (author)

  10. Intracellular targeting of mercaptoundecahydrododecaborate (BSH) to malignant glioma by transferrin-PEG liposomes for boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    Doi, Atsushi; Miyatake, Shin-ichi; Iida, Kyouko

    2006-01-01

    Malignant glioma is one of the most difficult tumor to control with usual therapies. In our institute, we select boron neutron capture therapy (BNCT) as an adjuvant radiation therapy after surgical resection. This therapy requires the selective delivery of high concentration of 10 B to malignant tumor tissue. In this study, we focused on a tumor-targeting 10 B delivery system (BDS) for BNCT that uses transferrin-conjugated polyethylene-glycol liposome encapsulating BSH (TF-PEG liposome-BSH) and compared 10 B uptake of the tumor among BSH, PEG liposome-BSH and TF-PEG liposome-BSH. In vitro, we analyzed 10 B concentration of the cultured human U87Δ glioma cells incubated in medium containing 20 μg 10 B/ml derived from each BDS by inductively coupled plasma atomic emission spectrometry (ICP-AES). In vivo, human U87Δ glioma-bearing nude mice were administered with each BDS (35mg 10 B/kg) intravenously. We analyzed 10 B concentration of tumor, normal brain and blood by ICP-AES. The TF-PEG liposome-BSH showed higher absolute concentration more than the other BDS. Moreover, TF-PEG liposome-BSH decreased 10 B concentration in blood and normal tissue while it maintained high 10 B concentration in tumor tissue for a couple of days. This showed the TF-PEG liposome-BSH caused the selective delivery of high concentration of 10 B to malignant tumor tissue. The TF-PEG liposome-BSH is more potent BDS for BNCT to obtain absolute high 10 B concentration and good contrast between tumor and normal tissue than BSH and PEG liposome-BSH. (author)

  11. Utilization of thymine analogue as a boron carrier for neutron capture therapy

    International Nuclear Information System (INIS)

    Zhang, Z.H.; Oda, Y.; Takagaki, M.

    1993-01-01

    The BNCT effect of 5'- carboranyl uridine (5'-CU), one of a most powerful candidate of thymine analogues as a boron carrier, was investigated on experimental brain tumor models. 5'-CU was highly accumulated into tumor cells through its multi-affinity potential to a variety of subcellular fractions of DNA/RNA and proteins. The boron concentration in tumor was more than 100 ppm, and its tumor/normal brain ratio was more than 11. Thermal neutron dose yielding 37% surviving fraction on cultured glioma cells was 3.7x10 12 nvt which was lower than that of control dose of 5.8x10 12 nvt. However, α-autoradiogram revealed that 5'-CU tightly binded to a variety of normal brain structures; choloid plexus, ependymal layer and so on. Indeed, the mean surviving fraction of brain tumor rats after BNCT using 5'-CU was slightly lower than that of control rats which did not received neutrons and 5'-CU. Furthermore its cytotoxicity was not low enough, 1/10-1/20 dose of rat LD 50 was required as a therapeutic dose. We are now under investigation of its clinical applicability as a boron carrier through its chemical modification in order to circumvent those problems, or warrant of further experiments in this area. (author)

  12. Folic acid-conjugated 4-amino-phenylboronate, a boron-containing compound designed for boron neutron capture therapy, is an unexpected agonist for human neutrophils and platelets.

    Science.gov (United States)

    Achilli, Cesare; Jadhav, Sushilkumar A; Guidetti, Gianni F; Ciana, Annarita; Abbonante, Vittorio; Malara, Alessandro; Fagnoni, Maurizio; Torti, Mauro; Balduini, Alessandra; Balduini, Cesare; Minetti, Giampaolo

    2014-05-01

    Boron neutron capture therapy (BNCT) is an anticancer treatment based on the accumulation in the tumor cells of (10) B-containing molecules and subsequent irradiation with low-energy neutrons, which bring about the decay of (10) B to very toxic (7) Li(3+) and (4) He(2+) ions. The effectiveness of BNCT is limited by the low delivery and accumulation of the used (10) B-containing compounds. Here, we report the development of folic acid-conjugated 4-amino-phenylboronate as a novel possible compound for the selective delivery of (10) B in BNCT. An extensive analysis about its biocompatibility to mature blood cells and platelet progenitors revealed that the compound markedly supports platelet aggregation, neutrophil oxidative burst, and inhibition of megakaryocyte development, while it does not have any manifest effect on red blood cells. © 2013 John Wiley & Sons A/S.

  13. Evaluation of carboranylporphyrins as boron delivery agents for neutron capture therapy

    International Nuclear Information System (INIS)

    Kawabata, Shinji; Barth, Rolf F.; Yang, Weilian; Wu, Gong; Binns, Peter J.; Riley, Kent J.; Ongayi, Owendi; Gottumukkala, Vijay; Vicente, Graca H.

    2006-01-01

    The goals of the present study were two-fold. First, to determine the biodistribution of three carboranyl-porphyrins, designated H 2 DCP, H 2 TCP and H 2 TBP following intracerebral (i.c.) administration by means of convection enhanced delivery (CED) to F98 glioma bearing rats. Tumor boron concentrations immediately after CED were 36 and 88 μg/g for H 2 DCP and H 2 TCP, respectively, and were 103 and 62 μg/g for H 2 TCP and H 2 TBP, respectively, 24h after termination of CED. The corresponding normal brain concentrations were 5.2, 3.3 and 0.8 μg/g, and blood and liver concentrations all were 2 TCP and H 2 TBP as boron delivery agents in F98 glioma bearing rats. BNCT was carried out at the Massachusetts Institute of Technology (MIT) Research Reactor (MITRR) 24 h after CED of 200 μl of either 0.5 mg of H 2 TCP or H 2 TBP. Untreated control rats all died within 29 days after tumor implantation and had a mean survival time (MST) of 23±3 days and irradiated controls had a MST of 27±3 days. Animals that received H 2 TCP by CED, followed by BNCT, had a MST of 35±4 days and animals received H 2 TBP had a MST of 44±10 days. Further studies were carried out using H 2 TBP at a dose of 0.2 mg administered by a Harvard pump, either alone or in combination with i.v. BPA, and the corresponding MSTs were 34±3 d and 43±9 d, respectively. Histopathologic examination of the brains of animals that died revealed large numbers of porphyrin laden macrophages and extracellular accumulations of free porphyrin indicating that tumor cell uptake was suboptimal. Further studies are planned to synthesize and evaluate new compounds that will have enhanced cellular uptake and efficacy as boron delivery agents for NCT. (author)

  14. Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a (10)BSH-containing WOW emulsion.

    Science.gov (United States)

    Yanagie, Hironobu; Higashi, Syushi; Seguchi, Koji; Ikushima, Ichiro; Fujihara, Mituteru; Nonaka, Yasumasa; Oyama, Kazuyuki; Maruyama, Syoji; Hatae, Ryo; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Tomoko; Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Narabayashi, Masaru; Kajiyama, Tetsuya; Maruhashi, Akira; Ono, Koji; Nakajima, Jun; Ono, Minoru; Takahashi, Hiroyuki; Eriguchi, Masazumi

    2014-06-01

    A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a (10)BSH-containing water-in-oil-in-water emulsion ((10)BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that (10)BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. A method to build an analytic model of the 10B(n,alpha)7Li reaction rate space distribution for boron neutron capture therapy (BNCT).

    Science.gov (United States)

    Morand, Josselin; Moss, Raymond; Hachem, Sabet; Sauerwein, Wolfgang

    2009-07-01

    This work provides the basis of a methodology to build a deterministic model for the spatial distribution of the (10)B(n,alpha)(7)Li reaction rate in boron neutron capture therapy (BNCT), as a function of space variables, boron concentration and beam incidence angle in homogeneous isotropic environments but also in different heterogeneous environments. Building the analytic function in a simple homogeneous environment with numerical methods leads to a mathematical formulation of the (10)B(n,alpha)(7)Li reactions rate.

  16. Synovectomy by neutron capture in boron

    International Nuclear Information System (INIS)

    Vega C, H.R.

    2002-01-01

    The rheumatoid arthritis is an illness which affect approximately at 3% of the World population. This illness is characterized by the inflammation of the joints which reduces the quality of life and the productivity of the patients. Since, it is an autoimmune illness, the inflammation is due to the overproduction of synovial liquid by the increase in the quantity of synoviocytes. The rheumatoid arthritis does not have a definitive recovery and the patients have three options of treatment: the use of drugs, the surgery and the radio synovectomy. The synovectomy by neutron capture in Boron is a novel proposal of treatment of the rheumatoid arthritis that consists in using a charged compound with Boron 10 that is preferently incorporated in the synoviocytes and to a less extent in the rest of surrounding tissues of the joint. Then, the joint is exposed to a thermal neutron field that induces the reaction (n, α) in the 10 B. the products of this reaction place their energy inside synoviocytes producing their reduction and therefore the reduction of the joint inflammation. Since it is a novel procedure, the synovectomy by neutron capture in boron has two problems: the source design and the design of the adequate drug. In this work it has been realized a Monte Carlo study with the purpose to design a moderating medium that with a 239 Pu Be source in its center, produces a thermal neutron field. With the produced neutron spectra, the neutrons spectra and neutron doses were calculated in different sites inside a model of knee joint. In Monte Carlo studies it is necessary to know the elemental composition of all the joint components, for the case of synovia and the synovial liquid this information does not exist in such way that it is supposed that its composition is equal than the water. In this work also it has been calculated the kerma factors by neutrons of synovia and the synovial liquid supposing that their elemental composition are similar to the blood tissue

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

    Science.gov (United States)

    Rasouli, Fatemeh S; Masoudi, S Farhad

    2015-02-01

    High-energy neutrons, named fast neutrons which have a number of undesirable biological effects on tissue, are a challenging problem in beam designing for Boron Neutron Capture Therapy, BNCT. In spite of this fact, there is not a widely accepted criterion to guide the beam designer to determine the appropriate contribution of fast neutrons in the spectrum. Although a number of researchers have proposed a target value for the ratio of fast neutron flux to epithermal neutron flux, it can be shown that this criterion may not provide the optimum treatment condition. This simulation study deals with the determination of the optimum contribution of fast neutron flux in the beam for BNCT of deep-seated tumors. Since the dose due to these high-energy neutrons damages shallow tissues, delivered dose to skin is considered as a measure for determining the acceptability of the designed beam. To serve this purpose, various beam shaping assemblies that result in different contribution of fast neutron flux are designed. The performances of the neutron beams corresponding to such configurations are assessed in a simulated head phantom. It is shown that the previously used criterion, which suggests a limit value for the contribution of fast neutrons in beam, does not necessarily provide the optimum condition. Accordingly, it is important to specify other complementary limits considering the energy of fast neutrons. By analyzing various neutron spectra, two limits on fast neutron flux are proposed and their validity is investigated. The results show that considering these limits together with the widely accepted IAEA criteria makes it possible to have a more realistic assessment of sufficiency of the designed beam. Satisfying these criteria not only leads to reduction of delivered dose to skin, but also increases the advantage depth in tissue and delivered dose to tumor during the treatment time. The Monte Carlo Code, MCNP-X, is used to perform these simulations. Copyright © 2014

  18. Abscopal effect of boron neutron capture therapy (BNCT). Proof of principle in an experimental model of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trivillin, Veronica A.; Monti Hughes, Andrea; Schwint, Amanda E. [Comision Nacional de Energia Atomica (CNEA), Department of Radiobiology, B1650KNA San Martin, Provincia Buenos Aires (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Pozzi, Emiliano C.C.; Curotto, Paula [Centro Atomico Ezeiza, Comision Nacional de Energia Atomica (CNEA), Department of Research and Production Reactors, Provincia Buenos Aires (Argentina); Colombo, Lucas L. [Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Instituto de Oncologia Angel H. Roffo, Ciudad Autonoma de Buenos Aires (Argentina); Thorp, Silvia I.; Farias, Ruben O. [Comision Nacional de Energia Atomica (CNEA), Department of Instrumentation and Control, Provincia Buenos Aires (Argentina); Garabalino, Marcela A. [Comision Nacional de Energia Atomica (CNEA), Department of Radiobiology, B1650KNA San Martin, Provincia Buenos Aires (Argentina); Gonzalez, Sara J. [Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Comision Nacional de Energia Atomica (CNEA), Department of Instrumentation and Control, Provincia Buenos Aires (Argentina); Santa Cruz, Gustavo A. [Comision Nacional de Energia Atomica (CNEA), Department of Boron Neutron Capture Therapy, Provincia Buenos Aires (Argentina); Carando, Daniel G. [Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Universidad de Buenos Aires, Faculty of Exact and Natural Sciences, Ciudad Autonoma de Buenos Aires (Argentina)

    2017-11-15

    The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 x 10{sup 6} DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 x 10{sup 6} DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm{sup 3}. In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm{sup 3}. The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Burns, Jr., Thomas Dean [Univ. of Virginia, Charlottesville, VA (United States)

    1995-05-01

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

  20. Abscopal effect of boron neutron capture therapy (BNCT). Proof of principle in an experimental model of colon cancer

    International Nuclear Information System (INIS)

    Trivillin, Veronica A.; Monti Hughes, Andrea; Schwint, Amanda E.; Pozzi, Emiliano C.C.; Curotto, Paula; Colombo, Lucas L.; Thorp, Silvia I.; Farias, Ruben O.; Garabalino, Marcela A.; Gonzalez, Sara J.; Santa Cruz, Gustavo A.; Carando, Daniel G.

    2017-01-01

    The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 x 10 6 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 x 10 6 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm 3 . In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm 3 . The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect. (orig.)

  1. Boron Neutron Capture Therapy at the TRIGA Mark II of Pavia, Italy - The BNCT of the diffuse tumours

    International Nuclear Information System (INIS)

    Altieri, S.; Bortolussi, S.; Stella, S.; Bruschi, P.; Gadan, M.A.

    2008-01-01

    The selectivity based on the B distribution rather than on the irradiation field makes Boron neutron Capture Therapy (BNCT) a valid option for the treatment of the disseminated tumours. As the range of the high LET particles is shorter than a cell diameter, the normal cells around the tumour are not damaged by the reactions occurring in the tumoral cells. PAVIA 2001: first treatment of multiple hepatic metastases from colon ca by BNCT and auto-transplantation technique: TAOrMINA project. The liver was extracted after BPA infusion, irradiated in the Thermal Column of the Pavia TRIGA Mark II reactor, and re-implanted in the patient. Two patients were treated, demonstrating the feasibility of the therapy and the efficacy in destroying the tumoral nodules sparing the healthy tissues. In the last years, the possibility of applying BNCT to the lung tumours using epithermal collimated neutron beams and without explanting the organ, is being explored. The principal obtained results of the BNCT research are presented, with particular emphasis on the following aspects: a) the project of a new thermal column configuration to make the thermal neutron flux more uniform inside the explanted liver, b) the Monte Carlo study by means of the MCNP code of the thermal neutron flux distribution inside a patient's thorax irradiated with epithermal neutrons, and c) the measurement of the boron concentration in tissues by (n,α) spectroscopy and neutron autoradiography. The dose distribution in the thorax are simulated using MCNP and the anthropomorphic model ADAM. To have a good thermal flux distribution inside the lung epithermal neutrons must be used, which thermalize crossing the first tissue layers. Thermal neutrons do not penetrate and the obtained uniformity is poor. In the future, the construction of a PGNAA facility using a horizontal channel of the TRIGA Mark II is planned. With this method the B concentration can be measured also in liquid samples (blood, urine) and in those

  2. Study of the interaction of boron-containing amino acids for the neutron capture therapy with biologically interesting compounds by using 'three-spot zone electrophoresis'

    International Nuclear Information System (INIS)

    Kitaoka, Yoshinori; Kobayashi, Mitsue; Morimoto, Tsuguhiro; Kirihata, Mitsunori; Ichimoto, Itsuo.

    1995-01-01

    As the boron carriers for boron neutron capture therapy, p-borono phenylalanine (BPA) is the boron compound which has been clinically used together with sodium borocaptate. It was found by the electrophoresis behavior that the BPA interacted with organic carboxylic acids in its dissolved state. In this paper, the electrophoresis behavior of general amino acids as seen in three-spot zone electrophoresis and the peculiar interaction of the amino acids having dihydroxyboryl radical are described. Zone electrophoresis has been developed as separation means, and three-spot process excludes the errors due to accidental factors as far as possible. The behaviors of zone electrophoresis of ordinary neutral amino acids, orthoboric acid and p-BPA are reported. For utilizing the features of boron neutron capture therapy, it is necessary to develop the carrier which is singularly taken into cancer cells. There is not a good method for discriminating normal cells and cancer cells. As for the administration of BPA to patients, its solubility is insufficient, therefore, its fructose complex has been used. The research on the biochemical peculiarity of boron is important. (K.I.)

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  4. Neutron capture therapy. Principles and applications

    International Nuclear Information System (INIS)

    Sauerwein, Wolfgang A.G.; Moss, Raymond; Wittig, Andrea; Nakagawa, Yoshinobu

    2012-01-01

    State of the art report on neutron capture therapy. Summarizes the progress made in recent decades. Multidisciplinary approach. Written by the most experienced specialists Neutron capture therapy (NCT) is based on the ability of the non-radioactive isotope boron-10 to capture thermal neutrons with very high probability and immediately to release heavy particles with a path length of one cell diameter. This in principle allows for tumor cell-selective high-LET particle radiotherapy. NCT is exciting scientifically but challenging clinically, and a key factor in success is close collaboration among very different disciplines. This book provides a comprehensive summary of the progress made in NCT in recent years. Individual sections cover all important aspects, including neutron sources, boron chemistry, drugs for NCT, dosimetry, and radiation biology. The use of NCT in a variety of malignancies and also some non-malignant diseases is extensively discussed. NCT is clearly shown to be a promising modality at the threshold of wider clinical application. All of the chapters are written by experienced specialists in language that will be readily understood by all participating disciplines.

  5. Sodium borocaptate (BSH) for Boron Neutron Capture Therapy (BNCT) in the hamster cheek pouch oral cancer model: boron biodistribution at 9 post administration time-points

    International Nuclear Information System (INIS)

    Garabalino, M.A.; Heber, E.M.; Monti, Hughes A.; Molinari, A.J.; Pozzi, E.C.C.; Trivillin, V.A.; Schwint, Amanda E.

    2011-01-01

    The therapeutic success of Boron Neutron Capture Therapy (BNCT) depends centrally on boron concentration in tumor and healthy tissue. We previously demonstrated the therapeutic efficacy of boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) as boron carriers for BNCT in the hamster cheek pouch oral cancer model. Given the clinical relevance of sodium mercaptoundecahydro-closo-dodecaborate (BSH) as a boron carrier, the aim of the present study was to expand the ongoing BSH biodistribution studies in the hamster cheek pouch oral cancer model. In particular, we studied 3 additional post-administration time-points and increased the sample size corresponding to the time-points evaluated previously, to select more accurately the post-administration time at which neutron irradiation would potentially confer the greatest therapeutic advantage. BSH was dissolved in saline solution in anaerobic conditions to avoid the formation of the dimer BSSB and its oxides which are toxic. The solution was injected intravenously at a dose of 50 mg 10 B/kg (88 mg BSH / kg). Different groups of animals were killed humanely at 7, 8, and 10 h after administration of BSH. The sample size corresponding to the time-points 3, 4, 6, 9 and 12 h was increased. Samples of blood, tumor, precancerous tissue, normal pouch tissue, cheek mucosa, parotid gland, palate, skin, tongue, spinal cord marrow, brain, liver, kidney, spleen and lung were processed for boron measurement by Optic Emission Spectroscopy (ICP-OES). Boron concentration in tumor peaked to 24-34 ppm, 3-10 h post-administration of BSH, with a spread in values that resembled that previously reported in other experimental models and human subjects. The boron concentration ratios tumor/normal pouch tissue and tumor/blood ranged from 1.3 to 1.8. No selective tumor uptake was observed at any of the time points evaluated. The times post-administration of BSH that would be therapeutically most useful would be 5, 7 and 9 h. The

  6. Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.

    Science.gov (United States)

    Wang, Ling-Wei; Chen, Yi-Wei; Ho, Ching-Yin; Hsueh Liu, Yen-Wan; Chou, Fong-In; Liu, Yuan-Hao; Liu, Hong-Ming; Peir, Jinn-Jer; Jiang, Shiang-Huei; Chang, Chi-Wei; Liu, Ching-Sheng; Lin, Ko-Han; Wang, Shyh-Jen; Chu, Pen-Yuan; Lo, Wen-Liang; Kao, Shou-Yen; Yen, Sang-Hue

    2016-05-01

    To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA-positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Synthesis and characterization of boron fenbufen and its F-18 labeled homolog for boron neutron capture therapy of COX-2 overexpressed cholangiocarcinoma.

    Science.gov (United States)

    Yeh, Chun-Nan; Chang, Chi-Wei; Chung, Yi-Hsiu; Tien, Shi-Wei; Chen, Yong-Ren; Chen, Tsung-Wen; Huang, Ying-Cheng; Wang, Hsin-Ell; Chou, You-Cheng; Chen, Ming-Huang; Chiang, Kun-Chun; Huang, Wen-Sheng; Yu, Chung-Shan

    2017-09-30

    Boron neutron capture therapy (BNCT) is a binary therapy that employs neutron irradiation on the boron agents to release high-energy helium and alpha particles to kill cancer cells. An optimal response to BNCT depends critically on the time point of maximal 10 B accumulation and highest tumor to normal ratio (T/N) for performing the neutron irradiation. The aggressive cholangiocarcinoma (CCA) representing a liver cancer that overexpresses COX-2 enzyme is aimed to be targeted by COX-2 selective boron carrier, fenbufen boronopinacol (FBPin). Two main works were performed including: 1) chemical synthesis of FBPin as the boron carrier and 2) radiochemical labeling with F-18 to provide the radiofluoro congener, m-[ 18 F]fluorofenbufen ester boronopinacol (m-[ 18 F]FFBPin), to assess the binding affinity, cellular accumulation level and distribution profile in CCA rats. FBPin was prepared from bromofenbufen via 3 steps with 82% yield. The binding assay employed [ 18 F]FFBPin to compete FBPin for binding to COX-1 (IC 50 =0.91±0.68μM) and COX-2 (IC 50 =0.33±0.24μM). [ 18 F]FFBPin-derived 60-min dynamic PET scans predict the 10 B-accumulation of 0.8-1.2ppm in liver and 1.2-1.8ppm in tumor and tumor to normal ratio=1.38±0.12. BNCT was performed 40-55min post intravenous administration of FBPin (20-30mg) in the CCA rats. CCA rats treated with BNCT display more tumor reduction than that by NCT with respect of 2-[ 18 F]fluoro-2-deoxy glucose uptake in the tumor region of interest, 20.83±3.00% (n=12) vs. 12.83±3.79% (n=10), P=0.05. The visualizing agent [ 18 F]FFBPin resembles FBPin to generate the time-dependent boron concentration profile. Optimal neutron irradiation period is thus determinable for BNCT. A boron-substituted agent based on COX-2-binding features has been prepared. The moderate COX-2/COX-1 selectivity index of 2.78 allows a fair tumor selectivity index of 1.38 with a mild cardiovascular effect. The therapeutic effect from FBPin with BNCT warrants a proper

  8. First evaluation of the biologic effectiveness factors of boron neutron capture therapy (BNCT) in a human colon carcinoma cell line.

    Science.gov (United States)

    Dagrosa, Maria Alejandra; Crivello, Martín; 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

    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 ((10)BPA) and for 2,4-bis (α,β-dihydroxyethyl)-deutero-porphyrin IX ((10)BOPP). Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm (10)B) + neutrons, (2) BOPP (10 ppm (10)B) + neutrons, (3) neutrons alone, and (4) gamma rays ((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(9) n/cm(2) sec). 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 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. 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 biologic model and could be useful for future experimental studies for the application of BNCT to colon carcinoma

  9. Studies for the application of Boron neutron capture therapy (BNCT) to the treatment of differentiated thyroid cancer (CDT)

    International Nuclear Information System (INIS)

    Carpano, Marina; Thomasz, Lisa; Perona, Marina; Juvenal, Guillermo J.; Pisarev, Mario; Dagrosa, Maria A.; Nievas, Susana I.; Pozzi, Emiliano; Thorp, Silvia

    2009-01-01

    Boron neutron capture therapy (BNCT) is a high linear energy transfer (LET) radiotherapy for cancer, which it is based on the nuclear reaction that occurs when boron-10 that it is a non radioactive isotope of the natural elemental boron, is irradiated with low energy thermal neutrons to produce an alpha particle and a nucleus of lithium-7. Both particles have a range smaller than the diameter of a cell causing cell tumor death without significant damage to the surrounding normal tissues. In previous studies we have shown that BNCT can be a possibility for the treatment of undifferentiated thyroid cancer (UTC). However, more than 80 % of patients with thyroid neoplasm present differentiated carcinoma (CDT). These carcinomas are treated by surgery followed by therapy with 131 I and mostly these forms are well controlled. But in some patients recurrence of the tumor is observed. BNCT can be an alternative for these patients in who the tumor lost the capacity to concentrate iodide. The aim of these studies was to evaluate the possibility of treating differentiated thyroid cancer by BNCT. Materials and Methods: The human cell lines of follicular (WRO) and papillary carcinomas (TPC-1) were grown in RPMI and modified DMEM medium respectively. Both supplemented with 10 % of SFB. The cell line of thyroid rat, FRTL-5, used as control normal, was cultured in DMEM/F12. The uptakes of 125 I and p-borophenylalanine BPA (6.93mM) were studied. The intracellular boron concentration was measured by inductively coupled plasma optical emission spectroscopy (ICP-OES) at 2 hr post incubation. The NIH strain of male nude mice, aged 6 to 8 weeks and weighing 20 to 25 g were implanted (s.c) in the back right flank with different concentrations of tumor cells. The size of the tumors was measured with a caliper twice or three times a week and the volume was calculated according the following formulae: A 2 x B/2 (were A is the width and B is the length). To evaluate the BPA uptake, animals

  10. Boron-11 MRI and MRS of intact animals infused with a boron neutron capture agent

    International Nuclear Information System (INIS)

    Kabalka, G.W.; Davis, M.; Bendel, P.

    1988-01-01

    Boron neutron capture therapy (BNCT) depends on the delivery of boron-containing drugs to a targeted lesion. Currently, the verification and quantification of in vivo boron content is a difficult problem. Boron-11 spectroscopy was utilized to confirm the presence of a dimeric sulfhydryl dodecaborane BNCT agent contained in an intact animal. Spectroscopy experiments revealed that the decay time of transverse magnetization of the boron-11 spins was less than 1 ms which precluded the use of a 2DFT imaging protocol. A back-projection protocol was developed and utilized to generate the first boron-11 image of a BNCT agent in the liver of an intact Fisher 344 rat

  11. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

    International Nuclear Information System (INIS)

    Nigg, David W.

    2012-01-01

    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.

  12. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Determination of boron-containing compounds in urine and blood plasma from boron neutron capture therapy patients. The importance of using coupled techniques.

    Science.gov (United States)

    Svantesson, Eva; Capala, Jacek; Markides, Karin E; Pettersson, Jean

    2002-10-15

    The necessity of using coupled techniques to analyze samples from boron neutron capture therapy (BNCT) patients prior to element-specific detection has been demonstrated. BNCT patients were infused with p-boronophenylalanine (BPA)-fructose complex before the therapy started. Urine and blood plasma samples were collected at different times after the start of the BPA administration and were run on a porous graphitic carbon column coupled on-line to an inductively coupled plasma-atomic emission spectrometer (ICP-AES) and an ICP time-of-flight mass spectrometer (TOF-MS). In addition to BPA, a possible metabolite to BPA and some minor boron-containing compounds, eluting close to the front, were also found in the urine and plasma samples. Because only the total concentration of boron has been measured so far in earlier studies, the suspected metabolite could not be detected, and this is the first report indicating its presence in urine and plasma of BNCT patients. The abundance of 10B in urine was about the same for BPA and its possible metabolite (98-99%). The ratio between the possible metabolite and BPA was found to differ in the urine from different patients. Most of the patients had a metabolite concentration of approximately 10 mol % of the BPA content in their urine 5-11 h after the start of the BPA administration. This ratio increased to between 30 and 80% when 24 h had passed. The ratio of metabolite to BPA was found to be lower in the plasma than in the urine samples at comparable time after the start of BPA infusion. Preliminary results from micro-LC-electrospray ionization (ESI)-MS/MS measurements on four urine samples indicate that the metabolite has a higher mass than BPA.

  14. Conceptual study of a compact accelerator-driven neutron source for radioisotope production, boron neutron capture therapy and fast neutron therapy

    CERN Document Server

    Angelone, M; Rollet, S

    2002-01-01

    The feasibility of a compact accelerator-driven device for the generation of neutron spectra suitable for isotope production by neutron capture, boron neutron capture therapy and fast neutron therapy, is analyzed by Monte Carlo simulations. The device is essentially an extension of the activator proposed by Rubbia left bracket CERN/LHC/97-04(EET) right bracket , in which fast neutrons are diffused and moderated within a properly sized lead block. It is shown that by suitable design of the lead block, as well as of additional elements of moderating and shielding materials, one can generate and exploit neutron fluxes with the spectral features required for the above applications. The linear dimensions of the diffusing-moderating device can be limited to about 1 m. A full-scale device for all the above applications would require a fast neutron source of about 10**1**4 s**-**1, which could be produced by a 1 mA, 30 MeV proton beam impinging on a Be target. The concept could be tested at the Frascati Neutron Gener...

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

    Energy Technology Data Exchange (ETDEWEB)

    Andoh, T. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Sudo, T. [Section of Translational Research, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fujita, I.; Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Moritake, H. [Department of Pediatrics, Miyazaki University, Kiyotake 889-1692 (Japan); Sugimoto, T. [Department of Pediatrics, Saiseikai Shigaken Hospital, Ritto 520-3046 (Japan); Sakuma, Y. [Department of Pathology, Hyogo Cancer Center, Akashi 673-0021 (Japan); Takeuchi, T. [Department of Pathology, Kochi University, Nangoku 783-8505 (Japan); Kawabata, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Kirihata, M. [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai 599-8531 (Japan); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Yayama, K. [Laboratory of Cardiovascular Pharmacology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Miyatake, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Fukumori, Y. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Ichikawa, H., E-mail: ichikawa@pharm.kobegakuin.ac.jp [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

    2011-12-15

    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 {sup 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).

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    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.

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

    Science.gov (United States)

    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. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    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.

    2011-01-01

    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).

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

    Science.gov (United States)

    Heber, Elisa M; Hawthorne, M Frederick; Kueffer, Peter J; Garabalino, Marcela A; Thorp, Silvia I; Pozzi, Emiliano C C; Monti Hughes, Andrea; Maitz, Charles A; Jalisatgi, Satish S; Nigg, David W; Curotto, Paula; Trivillin, Verónica A; Schwint, Amanda E

    2014-11-11

    The application of boron neutron capture therapy (BNCT) mediated by liposomes containing (10)B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%.

  20. Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model.

    Science.gov (United States)

    Yanagie, H; Maruyama, K; Takizawa, T; Ishida, O; Ogura, K; Matsumoto, T; Sakurai, Y; Kobayashi, T; Shinohara, A; Rant, J; Skvarc, J; Ilic, R; Kuhne, G; Chiba, M; Furuya, Y; Sugiyama, H; Hisa, T; Ono, K; Kobayashi, H; Eriguchi, M

    2006-01-01

    Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate (10)B atoms in the tumour cells. The delivery system consisted of polyethylene-glycol (PEG) binding liposomes (DPPC/cholesterol/DSPC-PEG2000) with an entrapped (10)B-compound and we evaluated the cytotoxic effects of intravenously injected (10)B-PEG-liposomes on human pancreatic carcinoma xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with (10)B-PEG-liposomes, growth of AsPC-1 tumours was suppressed relative to controls. Injection of (10)B-PEG-liposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of (10)B-PEG-liposomes can increase the retention of (10)B atoms by tumour cells, causing suppression of tumour growth in vivo, after thermal neutron irradiation.

  1. Current status of neutron capture therapy

    International Nuclear Information System (INIS)

    2001-05-01

    There are about 6000 new glioblastoma multiform brain tumours diagnosed each year in the United States of America alone. This cancer is usually fatal within six months of diagnosis even with current standard treatments. Research on boron neutron capture therapy (BNCT) has been considered as a method of potentially curing such cancers. There is a great interest at under-utilised research reactors institutions to identify new medical utilization, attractive to the general public. Neutron capture therapy is a true multidisciplinary topic with a large variety of individuals involved. This publication attempts to provide current information for all those thinking about being involved with NCT, based on the knowledge and experience of those who have pioneered the treatment. It covers the whole range of NCT from designing reactor conversions or new facilities, through to clinical trials and their effectiveness. However, since most work has been done with boron capture therapy for brain tumours using modified thermal research reactors, this tends to be the focus of the report. One of the factors which need to be addressed at the beginning is the timing of the further development of NCT facilities. It should be emphasised that all current work is still at the research stage. Many of those now involved believe that there is little need for many more research facilities until such time as the treatment shows more promising results. For this and other reasons discussed in the report, very serious consideration should be given by research reactor owners and operators before spending large sums of money converting their facilities for NCT

  2. Killing effect of carboranyl uridine on boron neutron capture reaction

    International Nuclear Information System (INIS)

    Takagaki, M.; Oda, Y.; Zhang, Z.

    1994-01-01

    This paper deals with the killing effect of carboranyl uridine (CU) on thermal neutron capture reaction in cultured glioma cell line (C6). The tumoricidal effect of CU for boron neutron capture therapy in the cultured cell system is presented. To assess the uptake of CU, the number of germ cells was determined by comparing protein concentrations of C6 cells in vitro with that of intracranially transplanted C6 tumor cells in vivo. To assess tumoricidal effects of CU, human glioma cells (T98G), containing 25 ppm natural boron of CU, were irradiated with various doses of thermal neutrons at a constant fluence rate. The uptake and killing effects of mercaptoboron and boric acid were also investigated as controls. Subcellular boron concentrations confirmed the selective affinity to the nucleic acid synthesis. CU was found to have an affinity to nucleic acid synthesis and to be accumulated into nucleus of tumor cells. The irradiation dose which yielded 37% survival rate in the case of CU and control were 3.78+12E nvt and 5.80+12E nvt, respectively. The killing effect of CU was slightly higher than that of B-SH or BA. The effective way of CU injection should be further studied to obtain the uniform CU uptake in tumor cells. (N.K.)

  3. Boron neutron capture therapy using mixed epithermal and thermal neutron beams in patients with malignant glioma-correlation between radiation dose and radiation injury and clinical outcome

    International Nuclear Information System (INIS)

    Kageji, Teruyoshi; Nagahiro, Shinji; Matsuzaki, Kazuhito; Mizobuchi, Yoshifumi; Toi, Hiroyuki; Nakagawa, Yoshinobu; Kumada, Hiroaki

    2006-01-01

    Purpose: To clarify the correlation between the radiation dose and clinical outcome of sodium borocaptate-based intraoperative boron neutron capture therapy in patients with malignant glioma. Methods and Materials: The first protocol (P1998, n = 8) prescribed a maximal gross tumor volume (GTV) dose of 15 Gy. In 2001, a dose-escalated protocol was introduced (P2001, n 11), which prescribed a maximal vascular volume dose of 15 Gy or, alternatively, a clinical target volume (CTV) dose of 18 Gy. Results: The GTV and CTV doses in P2001 were 1.1-1.3 times greater than those in P1998. The maximal vascular volume dose of those with acute radiation injury was 15.8 Gy. The mean GTV and CTV dose in long-term survivors with glioblastoma was 26.4 and 16.5 Gy, respectively. A statistically significant correlation between the GTV dose and median survival time was found. In the 11 glioblastoma patients in P2001, the median survival time was 19.5 months and 1- and 2-year survival rate was 60.6% and 37.9%, respectively. Conclusion: Dose escalation contributed to the improvement in clinical outcome. To avoid radiation injury, the maximal vascular volume dose should be <12 Gy. For long-term survival in patients with glioblastoma after boron neutron capture therapy, the optimal mean dose of the GTV and CTV was 26 and 16 Gy, respectively

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

    Science.gov (United States)

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

    2015-11-01

    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. 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. % 6LiOH solution for 95%-enriched Li-6. A phantom was constructed containing 10 wt. % 6LiOH solution based on the simulation results. Experimental characterization of the depth dose distributions of the

  5. Accelerator-based neutron capture therapy

    International Nuclear Information System (INIS)

    JONES, D.T.L.; Sabbert, J.K.

    1998-01-01

    The possibilities of neutron capture therapy (NCT) were mooted as long ago as 1936. This treatment modality depends on the uptake in tumours of a nucleus with a high thermal neutron capture cross section and subsequent exposure to a thermal neutron beam. The capture reaction which has received most attention is 10 B(n,a) 7 Li in which the high-LET products have ranges of the order of cell dimensions. The boron must therefore be taken up in the tumour cells themselves. The 157 Gd(n,Y) 158 Gd reaction has also been examined as it has a cross section 67 times greater than 10 B neutron capture. The low-LET products have longer ranges and therefore do not need to be taken up precisely in the tumour cells. The chemistry of Gd compounds are also well known as they are used as contrast agents in MRI. fe The first patients with advanced brain tumours were treated in the USA in the 1950's and in Japan in the 1960's using reactor beams and boron compounds, Some encouraging results were obtained. Reactor beams have energies in the MeV range end need to be moderated for NCT. However, thermal beams do riot have sufficient penetration for the treatment of deep-seated tumours and the generation of intense epithermal (keV) beams is now receiving considerable attention. Reactors themselves are not ideal for medical treatments: they cannot generally be located in hospitals because of safety factors and public resistance; they are often located at remote locations which are inconvenient and conventional fractionation may not be feasible; fixed horizontal beams have to be used resulting in limited treatment planning options. The use of low-energy accelerators to produce epithermal neutron beams is under serious consideration. These can be relatively small devices providing multi directional beams and which could be located in hospitals. They therefore offer an attractive alternative to reactor beams. The reactions considered most favourable are 7 Li(p,n) 7 Be and 9 Be(p,n) 9 B with

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

    Energy Technology Data Exchange (ETDEWEB)

    Fairchild, R.G.; Brownell, G.L. (eds.)

    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.

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

    International Nuclear Information System (INIS)

    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

  8. Neutron capture therapy with thermal neutrons at IRT MIFI

    International Nuclear Information System (INIS)

    Zajtsev, K.N.; Portnov, A.A.; Savkin, V.A.; Kulakov, V.N.; Khokhlov, V.F.; Shejno, I.N.; Vajnson, A.A.; Kozlovskaya, N.G.; Meshcherikova, V.V.; Mitin, V.N.; Yarmonenko, S.P.

    2001-01-01

    Combined preclinical investigations into neutron capture therapy are conducted. Malignant melanoma was adopted as the line of investigation; boron-containing and gadolinium-containing preparations were used during the neutron capture therapy working off. Preparations produce secondary varying radiations when used in tumor. Dogs with spontaneous melanoma were used for the experiments. Procedures for the irradiation of dogs by neutron beam as the stage before use for the treatment of oncology patients were finished off; efficiency of neutron beam influence on normal tissues during the irradiation of dogs with melanoma (and without it) in antitumor and side effect sense was estimated [ru

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

    International Nuclear Information System (INIS)

    Suzuki, Minoru; Sakurai, Yoshinori; Nagata, Kenji; Kinashi, Yuko; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira; Kato, Ituro; Fuwa, Nobukazu; Hiratsuka, Junichi; Imahori, Yoshio

    2006-01-01

    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

  10. Research needs for neutron capture therapy

    International Nuclear Information System (INIS)

    1995-01-01

    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

  11. Research needs for neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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. Dosimetry boron neutron capture therapy in liver cancer (hepatocellular carcinoma) by means of MCNP-code with neutron source from thermal column

    International Nuclear Information System (INIS)

    Irhas; Andang Widi Harto; Yohannes Sardjono

    2014-01-01

    Boron Neutron Capture Therapy (BNCT) using physics principle when B 10 (Boron-10) irradiated by low energy neutron (thermal neutron). Boron and thermal neutron reaction produced B 11m (Boron-11m) (t 1/2 =10 -2 s). B 11m decay emitted alpha, Li 7 (Lithium-7) particle and gamma ray. Irradiated time needed to ensure cancer dose enough. Liver cancer was primary malignant who located in liver (Hepatocellular carcinoma). Malignant in liver were different to metastatic from Breast, Colon Cancer, and the other. This condition was Metastatic Liver Cancer. Monte Carlo method used by Monte Carlo N-Particle (MCNP) Software. Probabilistic approach used for probability of interaction occurred and record refers to characteristic of particle and material. In this case, thermal neutron produced by model of Collimated Thermal Column Kartini Research Nuclear Reactor, Yogyakarta. Modelling organ and source used liver organ that contain of cancer tissue and research reactor. Variation of boron concentration was 20, 25, 30, 35, 40, 45, and 47 µg/g cancers. Output of MCNP calculation were neutron scattering dose, gamma ray dose and neutron flux from reactor. Neutron flux used to calculate alpha, proton and gamma ray dose from interaction of tissue material and thermal neutron. Variation of boron concentration result dose rate to every variation were 0,059; 0,072; 0,084; 0,098; 0.108; 0,12; 0,125 Gy/sec. Irradiation time who need to every concentration were 841,5 see (14 min 1 sec); 696,07 sec(11 min 36 sec); 593.11 sec (9 min 53 sec); 461,35 sec (8 min 30 sec); 461,238 sec (7 min 41 sec); 414,23 sec (6 min 54 sec); 398,38 sec (6 min 38 sec). Irradiating time could shortly when boron concentration more high. (author)

  13. A conceptual design of a beam-shaping assembly for boron neutron capture therapy based on deuterium-tritium neutron generators

    International Nuclear Information System (INIS)

    Martin, Guido; Abrahantes, Arian

    2004-01-01

    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

  14. The effect of ionizing radiation on the blood-brain-barrier (BBB): Considerations for the application of boron neutron capture therapy (BNCT) of brain tumors

    International Nuclear Information System (INIS)

    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, as an inseparable component, an element of ionizing radiation. 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. This paper has the following objectives: 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

  15. MODELING THE RADIATION SHIELDING OF BORON NEUTRON CAPTURE THERAPY BASED ON 2.4 MEV D-D NEUTRON GENERATOR FACILITY

    Directory of Open Access Journals (Sweden)

    Muhammad Mu’Alim

    2018-01-01

    PEMODELAN PERISAI RADIASI PADA FASILITAS BORON NEUTRON CAPTURE THERAPY BERBASIS GENERATOR NEUTRON D-D 2,4 MeV. Telah dimodelkan perisai radiasi pada fasilitas Boron Neutron Capture Therapy (BNCT berbasis reaksi D-D pada Neutron Generator 2,4 MeV dengan Beam Shaping Assembly (BSA yang telah didesain sebelumnya. Pemodelan ini dilakukan untuk memperoleh suatu desain perisai radiasi untuk fasilitas BNCT berbasis generator neutron 2,4 MeV. Pemodelan dilakukan dengan cara memvariasikan bahan dan ketebalan perisasi radiasi. Bahan yang dipilih adalah beton barit, parafin, polietilen terborasi dan timbal. Perhitungan dilakukan menggunakan program MCNPX dengan tally F4 untuk menentukan laju dosis yang keluar dari perisai radiasi. Desain periasi radiasi dinyatakan optimal jika radiasi yang dihasilkan diluar perisai radiasi tidak melebihi Nilai Batas Dosis (NBD yang telah ditentukan oleh BAPETEN. Hasilnya, diperoleh suatu desain perisai radiasi menggunakan lapisan utama beton barit setebal 100 cm yang mengelilingi ruangan 100 cm x 100 cm x 166,4 cm dan polietilen terborasi 40 cm yang mengelilingi bahan beton barit. Kemudian ditambahkan beton barit 10 cm dan polietilen terborasi 10 cm untuk mengurangi radiasi primer yang lurus dari BSA setelah keluar dari lapisan utama. Laju dosis terbesar adalah 4,58 μSv·jam-1 pada sel 227 dan laju dosis rata-rata yang dihasilkan adalah sebesar 0,65 µSv·jam-1. Nilai laju dosis tersebut masih dibawah ambang batas NBD yang diperbolehkan oleh BAPETEN untuk pekerja radiasi. Kata kunci: Perisai radiasi, tally, laju dosis radiasi, BSA, BNCT

  16. Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a 10BSH-containing WOW emulsion

    International Nuclear Information System (INIS)

    Yanagie, Hironobu; Higashi, Syushi; Seguchi, Koji; Ikushima, Ichiro; Fujihara, Mituteru; Nonaka, Yasumasa; Oyama, Kazuyuki; Maruyama, Syoji; Hatae, Ryo; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Tomoko; Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Narabayashi, Masaru; Kajiyama, Tetsuya; Maruhashi, Akira; Ono, Koji; Nakajima, Jun

    2014-01-01

    A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a 10 BSH-containing water-in-oil-in-water emulsion ( 10 BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that 10 BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC. - Highlights: • We started the pilot clinical study of BNCT to recurrence hepatic cancer. • The tumor size was remained stable during 3 months after BNCT(SD). • No adverse effect as a result of BNCT was observed during follow-up period. • 10 B-containing WOW emulsion can be applied as a novel intra-arterial boron carrier for BNCT for HCC

  17. Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits.

    Science.gov (United States)

    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 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.

  18. Novel amino-carboxy-dihydroboranes for neutron capture therapy

    International Nuclear Information System (INIS)

    Boehmel, T.

    1985-01-01

    The thesis discusses the following topics: I. Synthesis of boron compounds for the neutron capture therapy which are to meet the following requirements: 1. Low toxicity; 2. High boron content; 3. High enrichment and long retention time in the neoplastic tissue and simultaneous low concentration in blood and normal tissue; 4. Independent cytostatic effects; 5. Functional groups which allow a connection with polymers. II. Presentation of compounds with increased 10 B content. III. Examination of the distribution of boric substances in living organisms by means of a quantitative analysis of the boron content. (orig./PW) [de

  19. Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via 1H2O MRI: implications for boron neutron capture therapy of malignant brain tumours

    International Nuclear Information System (INIS)

    Medina, Daniel C; Li Xin; SpringerJr, Charles S

    2005-01-01

    In addition to its common usage as a tracer in metabolic and physiological studies, deuterium possesses anti-tumoural activity and confers protection against γ-irradiation. A more recent interest in deuterium emanates from the search for alternatives capable of improving neutron penetrance whilst reducing healthy tissue radiation dose deposition in boron neutron capture therapy of malignant brain tumours. Despite this potential clinical application, deuterium induces brain oedema, which is detrimental to neutron capture therapy. In this study, five adult male rats were titrated with deuterated drinking water while brain oedema was monitored via water proton magnetic resonance imaging. This report concludes that deuterium, as well as deuterium-induced brain oedema, possesses a uniform brain bio-distribution. At a steady-state blood fluid deuteration value of 16%, when the deuterium isotope fraction in drinking water was 25%, a mean oedematous volume change of 9 ± 2% (p-value <0.001) was observed in the rat brain-this may account for neurological and behavioural abnormalities found in mammals drinking highly deuterated water. In addition to characterizing the pharmaco-thermodynamics of deuterium-induced oedema, this report also estimates the impact of oedema on thermal neutron enhancement and effective dose reduction factors using simple linear transport calculations. While body fluid deuteration enhances thermal neutron flux penetrance and reduces dose deposition, oedema has the opposite effect because it increases the volume of interest, e.g., the brain volume. Thermal neutron enhancement and effective dose reduction factors could be reduced by as much as ∼10% in the presence of a 9% water volume increase (oedema)

  20. Morphometric and immunocytochemical analysis of melanoma samples for individual optimization of therapy for boron neutron capture (BNCT)

    International Nuclear Information System (INIS)

    Carpano, M; Dagrosa, A; Brandizzi, D; Nievas, S; Olivera, M S; Perona, M; Rodriguez, C; Cabrini, R; Juvenal, G; Pisarev, M

    2012-01-01

    Introduction: Tumors from different patients with the same histological diagnosis can show different responses to ionizing radiation including BNCT. Further knowledge about individual tumor characteristics is needed in order to optimize the individual application of this therapy. In previous studies we have shown different patterns of boron intracellular concentration in three human melanoma cell lines. When we performed xenografts with these cell lines in nude mice a wide range of boron concentrations in tumor was observed. We also evaluated the tumor temperature obtained by thermography. Objectives: The aim of this study was to evaluate the differences in the BPA uptake related to different histological and thermal characteristics of each tumor in nude mice bearing human melanoma. We also studied the proliferation and the vasculature in tumors by immunohistochemical studies and the relationship with the BPA uptake. Materials and Methodos: NIH nude mice of 6-8 weeks were implanted (s.c.) into the back right flank with 3.106 human melanoma cells (MELJ). To evaluate the BPA uptake, animals were injected at a dose of 350 mg/Kg b.w. (ip) and sacrificed 2 h post administration. Each sample of tumor was divided into two equal parts, one for uptake of B and another for histological studies. Boron measurements in tissues were performed by ICP-OES. For the histological studies, samples from the tumors were fixed in buffered 10% formaldehyde, embedded in paraffin and stained with hematoxylin and eosin (HE). Infrared imaging studies were performed the day before the biodistribution, measuring the tumor and body temperatures. Immunohistochemical studies were performed with antibodies Ki-67 and CD31. The first one is a marker of proliferative rate and the second one is a specific marker of endothelial cells which allows to identify the vasculature. Formaldehyde-fixed paraffin-embedded tissues and avidin biotin complex immunostaining were used. Results: Tumor BPA uptake showed

  1. "Sequential” Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

    Energy Technology Data Exchange (ETDEWEB)

    Ana J. Molinari; Andrea Monti Hughes; Elisa M. Heber; Marcela A. Garabalino; Veronica A. Trivillin; Amanda E. Schwint; Emiliano C. C. Pozzi; Maria E. Itoiz; Silvia I. Thorp; Romina F. Aromando; David W. Nigg; Jorge Quintana; Gustavo A. Santa Cruz

    2011-04-01

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10B carriers in tumors followed by irradiation with a thermal or epithermal neutron beam. The minor abundance stable isotope of boron, 10B, interacts with low energy (thermal) neutrons to produce high linear energy transfer (LET) a-particles and 7Li ions. These disintegration products are known to have a high relative biological effectiveness (RBE). Their short range (<10 {micro}m) would limit the damage to cells containing 10B (1,2). Thus, BNCT would target tumor tissue selectively, sparing normal tissue. Clinical trials of BNCT for the treatment of glioblastoma multiforme and/or melanoma and, more recently, head and neck tumors and liver metastases, using boronophenylalanine (BPA) or sodium mercaptoundecahydrododecaborane (BSH) as the 10B carriers, have been performed or are underway in Argentina, Japan, the US and Europe (e.g. 3-8). To date, the clinical results have shown a potential, albeit inconclusive, therapeutic advantage for this technique. Contributory translational studies have been carried out employing a variety of experimental models based on the implantation of tumor cells in normal tissue (e.g. 5).

  2. A simple and rapid method for measurement of 10B-para-boronophenylalanine in the blood for boron neutron capture therapy using fluorescence spectrophotometry

    International Nuclear Information System (INIS)

    Kashino, Genro; Fukutani, Satoshi; Suzuki, Minoru

    2009-01-01

    10 B deriving from 10 B-para-boronophenylalanine (BPA) and 10 B-borocaptate sodium (BSH) have been detected in blood samples of patients undergoing boron neutron capture therapy (BNCT) using prompt gamma ray spectrometer or Inductively Coupled Plasma (ICP) method, respectively. However, the concentration of each compound cannot be ascertained because boron atoms in both molecules are the target in these assays. Here, we propose a simple and rapid method to measure only BPA by detecting fluorescence based on the characteristics of phenylalanine. 10 B concentrations of blood samples from human or mice were estimated by the fluorescence intensities at 275 nm of a BPA excited by light of wavelength 257 nm using a fluorescence spectrophotometer. The relationship between fluorescence to increased BPA concentration showed a positive linear correlation. Moreover, we established an adequate condition for BPA measurement in blood samples containing BPA, and the estimated 10 B concentrations of blood samples derived from BPA treated mice were similar between the values obtained by our method and those by ICP method. This new assay will be useful to estimate BPA concentration in blood samples obtained from patients undergoing BNCT especially in a combination use of BSH and BPA. (author)

  3. Boron neutron capture therapy: A guide to the understanding of the pathogenesis of late radiation damage to the rat spinal cord

    International Nuclear Information System (INIS)

    Morris, G.M.; Whitehouse, E.M.; Hopewell, J.W.; Coderre, J.A.; Micca, P.

    1994-01-01

    Before the commencement of new boron neutron capture therapy (BNCT) clinical trials in Europe and North America, detailed information on normal tissue tolerance is required. In this study, the pathologic effects of BNCT on the central nervous system (CNS) have been investigated using a rat spinal cord model. The neutron capture agent used was 10 B-enriched sodium mercaptoundecahydro-closo-dodecaborate (BSH), at a dosage of 100 mg/kg body weight. Rats were irradiated on the thermal beam at the Brookhaven Medical Research Reactor. The large spine of vertebra T 2 was used as the lower marker of the irradiation field. Rats were irradiated with thermal neutrons alone to a maximum physical absorbed dose of 11.4 Gy, or with thermal neutrons in combination with BSH, to maximum absorbed physical doses of 5.7 Gy to the CNS parenchyma and 33.7 Gy to the blood in the vasculature of the spinal cord. An additional group of rats was irradiated with 250 kVp X-rays to a single dose of 35 Gy. Spinal cord pathology was examined between 5 and 12 months after irradiation. The physical dose of radiation delivered to the CNS parenchyma, using thermal neutron irradiation in the presence of BSH, was a factor of two to three lower than that delivered to the vascular endothelium, and could not account for the level of damage observed in the parenchyma. The histopathological observations of the present study support the hypothesis that the blood vessels, and the endothelial cells in particular, are the critical target population responsible for the lesions seen in the spinal cord after BNCT type irradiation and by inference, after more conventional irradiation modalities such as photons or fast neutrons. 30 refs., 6 figs., 1 tab

  4. Neutron activation of patients following boron neutron capture therapy of brain tumors at the high flux reactor (HFR) Petten (EORTC Trials 11961 and 11011).

    Science.gov (United States)

    Wittig, Andrea; Moss, Raymond L; Stecher-Rasmussen, Finn; Appelman, Klaas; Rassow, Jürgen; Roca, Antoanetta; Sauerwein, Wolfgang

    2005-12-01

    At the High Flux Reactor (HFR), Petten, The Netherlands, EORTC clinical trials of Boron Neutron Capture Therapy (BNCT) have been in progress since 1997. BNCT involves the irradiation of cancer patients by a beam of neutrons, with an energy range of predominantly 1 eV to 10 keV. The patient is infused with a tumor-seeking, (10)B-loaded compound prior to irradiation. Neutron capture in the (10)B atoms results in a high local radiation dose to the tumor cells, whilst sparing the healthy tissue. Neutron capture, however, also occurs in other atoms naturally present in tissue, sometimes resulting in radionuclides that will be present after treatment. The patient is therefore, following BNCT, radioactive. The importance of this induced activity with respect to the absorbed dose in the patient as well as to the radiation exposure of the staff has been investigated. As a standard radiation protection procedure, the ambient dose equivalent rate was measured on all patients following BNCT using a dose ratemeter. Furthermore, some of the patients underwent measurements using a gamma-ray spectrometer to identify which elements and confirm which isotopes are activated. Peak levels, i.e., at contact and directly after irradiation, are of the order of 40-60 muSv/h, falling to < 10 muSv/h 30-50 min after treatment. The average ambient dose equivalent in the first 2 h at a distance of 2 m from the patient is in the order of 2.5 muSv. The ambient dose equivalent rate in 2 m distance from the patient's head at the earliest time of leaving the reactor center (20 min after the end of treatment) is far less than 1 muSv/h. The main radioisotopes were identified as (38)Cl, (49)Ca, and (24)Na. Furthermore, in two patients, the isotopes (198)Au and (116m)In were also present. The initial activity is predominantly due to (49)Ca, whilst the remaining activity is predominantly due to (24)Na. The absorbed dose resulting from the activated isotopes in the irradiated volume is in the order of < 1

  5. Neutron capture therapy of ocular melanoma: dosimetry and microdosimetry approaches

    International Nuclear Information System (INIS)

    Pignol, J.P.; Methlin, G.; Abbe, J.C.; Lefebvre, O.; Sahel, J.

    1994-01-01

    Neutron capture therapy (NCT) aims at destroying cancerous cells with the α and 7 Li particles produced by the neutron capture reaction on 10 B. This note reports on the study of the boron distribution in tissues on an animal model (nude mice) xenografted with a human ocular melanoma after an i.p.injection of 2g/kg of 10 B-BPA and in cells cultured in the presence of 530 μmol/l of 10 B-BPA. A concentration of 64 ppm of 10 B in the active part of the tumour with a ratio of concentrations versus the skin of 3.7 are observed. Investigations on cells reveal the presence of boron in the cytoplasm. The biological, dosimetric and microdosimetric consequences of these findings are discussed. (authors). 15 refs., 2 tabs., 2 figs

  6. Large animal normal tissue tolerance with boron neutron capture

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  7. Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in hepatic cancer model for neutron capture therapy.

    Science.gov (United States)

    Yanagie, Hironobu; Dewi, Novriana; Higashi, Syushi; Ikushima, Ichiro; Seguchi, Koji; Mizumachi, Ryoji; Murata, Yuji; Morishita, Yasuyuki; Shinohara, Atsuko; Mikado, Shoji; Yasuda, Nakahiro; Fujihara, Mitsuteru; Sakurai, Yuriko; Mouri, Kikue; Yanagawa, Masashi; Iizuka, Tomoya; Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shin-Ichiro; Tanaka, Hiroki; Matsukawa, Takehisa; Yokoyama, Kazuhito; Fujino, Takashi; Ogura, Koichi; Nonaka, Yasumasa; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Yui, Sho; Nishimura, Ryohei; Ono, Koji; Takamoto, Sinichi; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Hasumi, Kenichiro; Takahashi, Hiroyuki

    2017-06-01

    Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a 10 BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment. We prepared the 10 BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto University Research Reactor with an average thermal neutron fluence of 5 × 10 12  n cm -2 . Morphological and pathological analyses were performed on Day 14 after neutron irradiation. Biodistribution results have revealed that 10 B atoms delivery with WOW emulsion was superior compared with those using iodized poppy-seed oil conventional emulsion. There was no dissemination in abdomen or lung metastasis observed after neutron irradiation in the groups treated with 10 BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non-injected group. Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the 10 BSH-entrapped WOW emulsion-injected group, indicating its feasibility to be applied as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The results of the current study have shown that entrapped 10 BSH has the potential to increase the range of therapies available for hepatocellular carcinoma which is considered to be one of the most difficult tumours to cure.

  8. 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)

    Science.gov (United States)

    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

  9. 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).

    Science.gov (United States)

    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

  10. Therapeutic efficacy and toxicity of a single and double application of boron neutron capture therapy (BNCT) in a hamster cheek pouch oral precancer model

    International Nuclear Information System (INIS)

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

    2012-01-01

    Tumor development from tissue with potentially malignant disorders (PMD) gives rise to second primary tumors. We previously demonstrated the partial inhibitory effect on tumor development of Boron Neutron Capture Therapy (BNCT) mediated by the boron compounds BPA (boronophenylalanine) and decahydrodecaborate (GB-10) in a hamster pouch oral precancer model. Seeking to optimize BNCT, the aim of the present study was to contribute to the knowledge of BNCT radiobiology for oral precancer and assess new BNCT protocols in terms of inhibition of tumor development and radiotoxicity. Groups of cancerized hamsters were locally exposed to single or double applications (2 weeks apart) of BPA-BNCT or (GB-10 + BPA)-BNCT at a total dose of 8Gy to tissue with PMD; to a single application of BPA-BNCT at 6Gy and to a double application (4 weeks apart) of BPA-BNCT or (BPA + GB-10)-BNCT at a total dose of 10Gy. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumor development from tissue with PMD and mucositis were followed for 8 months. The marked therapeutic efficacy of single applications of BNCT at 6 and 8Gy were associated to severe radiotoxicity. Dose fractionation into 2 applications reduced mucositis but also reduced therapeutic efficacy, depending on dose and interval between applications. A double application (4 weeks apart) of (GB-10 + BPA)-BNCT at a total dose of 10Gy rendered the best therapeutic advantage, i.e. 63% - 100% inhibition of tumor development with only slight mucositis in 67% of cases. The data reported herein show that issues such as dose levels and dose fractionation, interval between applications, and choice of boron compounds are pivotal to therapeutic advantage and must be tailored for a particular pathology and anatomic site. The present study determined treatment conditions that would contribute to optimize BNCT for precancer and that would warrant cautious assessment in a clinical scenario (author)

  11. Toward a clinical application of ex situ boron neutron capture therapy for lung tumors at the RA-3 reactor in Argentina

    Energy Technology Data Exchange (ETDEWEB)

    Farías, R. O.; Trivillin, V. A.; Portu, A. M.; Schwint, A. E.; González, S. J., E-mail: srgonzal@cnea.gov.ar [Comisión Nacional de Energía Atómica (CNEA), San Martín 1650, Argentina and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1033 (Argentina); 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. [Comisión Nacional de Energía Atómica (CNEA), San Martín 1650 (Argentina); Ferraris, S.; Santa María, J.; Rovati, O.; Lange, F. [CIDME, Universidad Maimónides, Buenos Aires 1405 (Argentina); Bortolussi, S. [Istituto Nazionale di Fisica Nucleare, Sezione di Pavia 27100 (Italy); Altieri, S. [Istituto Nazionale di Fisica Nucleare, Sezione di Pavia 27100, Italy and Dipartimento di Fisica, Università di Pavia, Pavia 27100 (Italy)

    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. Basic research of boron neutron-capture therapy for treatment of pancreatic cancer. Application of neutron radiography for visualization of boron compound on BNCT

    International Nuclear Information System (INIS)

    Yanagie, Hironobu

    1997-01-01

    The cytotoxic effects of locally injected 10 B-immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with 10 B-immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Histopathologically, hyalinization and necrosis were found in 10 B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10 B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. We prepared boronated PEG-binding bovine serum albumin ( 10 B-PEG-BSA). 10 B concentrations in AsPC-1, human pancreatic cancer cells (2 x 10 5 /well) obtained 24 hrs after incubation with 10 B-PEG-BSA was 13.01 ± 1.74 ppm. The number of 10 B atoms delivered to the tumor cells was calculated to be 7.83 x 10 11 at 24 hrs after incubation with 10 B-PEG-BSA. These data indicated that the 10 B-PEG-BSA could deliver a sufficient amount of 10 B atoms (more than 10 9 atoms/cell) to the tumor cells to induce cytotoxic effects after incubation upon thermal neutron irradiation. Neutron capture autoradiography by using an Imaging Plate (IP-NCR) was performed on AsPC-1 tumor-bearing mouse that had been given an intratumoral injection of 10 B-PEG BSA or 10 B-cationic liposome. We had demonstrated the 10 B-PEG BSA or 10 B-cationic liposome is taken up by AsPC-1 tumor tissue to a much greater extent than by normal tissues. (J.P.N.)

  13. Basic research of boron neutron-capture therapy for treatment of pancreatic cancer. Application of neutron radiography for visualization of boron compound on BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Yanagie, Hironobu [Tokyo Univ. (Japan). Inst. of Medical Science

    1997-02-01

    The cytotoxic effects of locally injected {sup 10}B-immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with {sup 10}B-immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Histopathologically, hyalinization and necrosis were found in {sup 10}B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of {sup 10}B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. We prepared boronated PEG-binding bovine serum albumin ({sup 10}B-PEG-BSA). {sup 10}B concentrations in AsPC-1, human pancreatic cancer cells (2 x 10{sup 5} /well) obtained 24 hrs after incubation with {sup 10}B-PEG-BSA was 13.01 {+-} 1.74 ppm. The number of {sup 10}B atoms delivered to the tumor cells was calculated to be 7.83 x 10{sup 11} at 24 hrs after incubation with {sup 10}B-PEG-BSA. These data indicated that the {sup 10}B-PEG-BSA could deliver a sufficient amount of {sup 10}B atoms (more than 10{sup 9} atoms/cell) to the tumor cells to induce cytotoxic effects after incubation upon thermal neutron irradiation. Neutron capture autoradiography by using an Imaging Plate (IP-NCR) was performed on AsPC-1 tumor-bearing mouse that had been given an intratumoral injection of {sup 10}B-PEG BSA or {sup 10}B-cationic liposome. We had demonstrated the {sup 10}B-PEG BSA or {sup 10}B-cationic liposome is taken up by AsPC-1 tumor tissue to a much greater extent than by normal tissues. (J.P.N.)

  14. “Sequential” Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Polycomplexes of Hyaluronic Acid and Borates in a Solid State and Solution: Synthesis, Characterization and Perspectives of Application in Boron Neutron Capture Therapy

    Directory of Open Access Journals (Sweden)

    Alexander N. Zelenetskii

    2018-02-01

    Full Text Available In this report, we propose a new polyborate fragment synthesis strategy along the whole chain of the polysaccharide hyaluronic acid (HA to produce boron neutron capture therapy (BNCT compounds. Under high pressure and deformatory solid-state conditions, polymolecular system formation takes place due to association of phase-specific transition components into a more or less distinct microscopic organization. Fourier transform infrared (FTIR spectroscopy shows that HA and polyborates form a network of cyclic polychelate complexes. HA acts as a multidentate ligand using carboxylic and hydroxyl proton donor groups to link oxygen atoms in B–O–B bonds and borate-anions B–O(−: O–H···O, O–H···(−O. With free electron pairs in heteroatoms –O(:···B, –N(:···B, HA can act simultaneously as an electron donor. Nuclear magnetic resonance (NMR with 13C and 1H reveals a preserved complex interaction after both solubilizing and attenuating the HA-polyborate system. Stability of the product in water, low cost, ease of synthesis and scalability of manufacturing indicate that HA-polyborate complexes might have advantages over current chemotherapeutic approaches in creating therapeutic agents for BNCT.

  16. Demonstration of a high-intensity neutron source based on a liquid-lithium target for Accelerator based Boron Neutron Capture Therapy.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. User's manual of a supporting system for treatment planning in boron neutron capture therapy. JAERI computational dosimetry system

    Energy Technology Data Exchange (ETDEWEB)

    Kumada, Hiroaki; Torii, Yoshiya [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2002-09-01

    A boron neutron capture therapy (BNCT) with epithermal neutron beam is expected to treat effectively for malignant tumor that is located deeply in the brain. It is indispensable to estimate preliminarily the irradiation dose in the brain of a patient in order to perform the epithermal neutron beam BNCT. Thus, the JAERI Computational Dosimetry System (JCDS), which can calculate the dose distributions in the brain, has been developed. JCDS is a software that creates a 3-dimensional head model of a patient by using CT and MRI images and that generates a input data file automatically for calculation neutron flux and gamma-ray dose distribution in the brain by the Monte Carlo code: MCNP, and that displays the dose distribution on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By treating CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is able to be made easily. The three-dimensional head image is editable to simulate the state of a head after its surgical processes such as skin flap opening and bone removal for the BNCT with craniotomy that are being performed in Japan. JCDS can provide information for the Patient Setting System to set the patient in an actual irradiation position swiftly and accurately. This report describes basic design and procedure of dosimetry, operation manual, data and library structure for JCDS (ver.1.0). (author)

  18. 'Sequential' Boron Neutron Capture Therapy (BNCT): A Novel Approach to BNCT for the Treatment of Oral Cancer in the Hamster Cheek Pouch Model

    International Nuclear Information System (INIS)

    Molinari, Ana J.; Pozzi, Emiliano C.C.; Hughes, Andrea Monti; Heber, Elisa M.; Garabalino, Marcela A.; Thorp, Silvia I.; Miller, Marcelo; Itoiz, Maria E.; Aromando, Romina F.; Nigg, David W.; Quintana, Jorge; Santa Cruz, Gustavo A.; Trivillin, Veronica A.; Schwint, Amanda E.

    2011-01-01

    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.

  19. Boron neutron capture therapy (BNCT) inhibits tumor development from precancerous tissue: An experimental study that supports a potential new application of BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Monti Hughes, A.; Heber, E.M. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Pozzi, E. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Department of Research and Production Reactors, Ezeiza Atomic Center, CNEA, Buenos Aires (Argentina); Nigg, D.W. [Idaho National Laboratory, Idaho Falls, Idaho (United States); Calzetta, O.; Blaumann, H.; Longhino, J. [Department of Nuclear Engineering, Bariloche Atomic Center, CNEA, Rio Negro (Argentina); Nievas, S.I. [Department of Chemistry, CNEA, Buenos Aires (Argentina); Aromando, R.F. [Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Itoiz, M.E. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Trivillin, V.A. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Schwint, A.E. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina)], E-mail: schwint@cnea.gov.ar

    2009-07-15

    We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na{sub 2}{sup 10}B{sub 10}H{sub 10}) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.

  20. Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Carpano, Marina; Perona, Marina; Rodriguez, Carla [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A. [Department of Boron Neutron Capture Therapy, National Atomic Energy Commission, San Martín (Argentina); Brandizzi, Daniel; Cabrini, Romulo [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); School of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Pisarev, Mario [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina); Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires (Argentina); Juvenal, Guillermo Juan [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina); Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.ar [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina)

    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

  1. Transferrin-loaded nido-carborane liposomes. Synthesis and intracellular targeting to solid tumors for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Nakamura, Hiroyuki; Miyajima, Yusuke; Kuwata, Yasuhiro; Maruyama, Kazuo; Masunaga, Shinichiro; Ono, Koji

    2006-01-01

    The boron ion cluster lipids, as a double-tailed boron lipid synthesized from heptadecanol, formed stable liposomes at 25% molar ratio toward DSPC with cholesterol. Transferrin was able to be introduced on the surface of boron liposomes (Tf-PEG-CL liposomes) by the coupling of transferrin to the PEG-CO 2 H moieties of PEG-CL liposomes. The biodistribution of Tf-PEG-CL liposomes showed that Tf-PEG-CL liposomes accumulated in tumor tissues and stayed there for a sufficiently long time to increase tumor:blood concentration ratio. A 10 B concentration of 22 ppm in tumor tissues was achieved by the injection of Tf-PEG-CL liposome at 7.2 mg/kg body weight 10 B in tumor-bearing mice. After neutron irradiation, the average survival rate of mice not treated with Tf-PEG-CL liposomes was 21 days, whereas that of the treated mice was 31 days. Longer survival rates were observed in the mice treated with Tf-PEG-CL liposomes; one of them even survived for 52 days after BNCT. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    D. W. Nigg

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  3. Preclinical and phase I studies of monoclonal antibodies in melanoma: Application to boron neutron capture therapy of melanoma

    International Nuclear Information System (INIS)

    Hersey, P.

    1989-01-01

    Monoclonal antibodies (MAbs) provide an attractive method of selectively localizing sufficient boron atoms around tumour cells to capture neutrons. Assuming that 10(8)-10(10) 10B atoms are needed for one capture event and that 10(3)-10(4) atoms can be coupled to each antibody molecule, then 10(5)-10(6) antibody molecules gathered on an individual cell will destroy that cell. Binding to normal tissues, on the other hand, would need to be at least 20-fold less than that to tumour tissues to avoid toxic effects of neutrons on surrounding tissues. Preclinical studies in animals show that several MAbs may bind to melanoma cells in sufficient quantities in vitro to localize the required amount of boron per cell. Whether this will occur in vivo, however, may depend not only on antigen density but a variety of other properties of the tumour cells and MAbs. These include the Ig class and affinity of the antibody and whether the antibody is internalized into the tumour cell. The ratio of uptake between tumour and normal tissue is governed by such factors as the percentage of tumour cells within a tumour expressing the antigen and whether the MAb react with normal tissues. Use of Fab or F(ab)2 preparations of the MAb may increase the uptake ratio by preventing uptake of MAb by cells with Fc receptors. In contrast to preclinical animal studies, tumour/normal tissue uptake ratios in phase I studies in humans have been disappointingly low.80 references

  4. A preclinical study of boron neutron capture therapy (BNCT) of spontaneous tumors in cats at RA-6 in Argentina

    International Nuclear Information System (INIS)

    Trivillin, Veronica A.; Heber, Elisa M.; Itoiz, Maria E.; Schwint, Amanda E.; Calzetta, Osvaldo A.; Blaumann, Hernan R.; Longhino, J.; Rao, Monica; Cantarelli, Maria de los A.

    2005-01-01

    BNCT is a binary treatment modality that combines irradiation with a thermal or epithermal neutron beam with tumor-seeking, boron containing drugs to produce selective irradiation of tumor tissue. Having demonstrated that BNCT mediated by boronophenylalanine (BPA) induced control of experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa with no damage to normal tissue we explored the feasibility and safety of treating spontaneous head and neck tumors, with particular focus on SCC, of terminal feline patients with low dose BPA-BNCT employing the thermal beam of RA-1. Having demonstrated partial tumor control with no radio toxic effects, the aim of the present study was to evaluate the effect of BPA-BNCT on tumor and normal tissue in 3 cases of spontaneous SCC in feline patients employing a higher neutron fluence than in the previous study. The present study was performed at RA-6 with the thermalized epithermal neutron beam. All three irradiations were successful. Except for an initial, moderate and reversible mucositis, no significant radio toxic effects were observed in terms of clinical follow-up, histological examination, biochemical analysis and assessment of autopsy material. Partial tumor control was evidenced in terms of growth inhibition and partial necrosis and improvement in the quality of life during the survival period. Optimization of the therapeutic efficacy of BNCT would require improvement in boron tumor targeting and strategies to increase in-depth dose in large tumors. (author)

  5. SU-E-J-100: Reconstruction of Prompt Gamma Ray Three Dimensional SPECT Image From Boron Neutron Capture Therapy(BNCT)

    International Nuclear Information System (INIS)

    Yoon, D; Jung, J; Suh, T

    2014-01-01

    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

  6. New functionalized mercaptoundecahydrododecaborate derivatives for potential application in boron neutron capture therapy: synthesis, characterization and dynamic visualization in cells.

    Science.gov (United States)

    Genady, Afaf R; Ioppolo, Joseph A; Azaam, Mohamed M; El-Zaria, Mohamed E

    2015-03-26

    A series of mercaptoundecahydrododecaborate (B12H11SH(2-), BSH) bearing mono- and dicarboxyalkyl derivatives was prepared, characterized, and their reactivity towards amidation and esterification in DMF was evaluated. Symmetrical alkylation of BSH was achieved by treatment with primary haloalkyl carboxylic acids in aqueous acetonitrile to produce S,S-bis(carboxyalkyl)sulfonium-undecahydro-closo-dodecaborate tetramethylammonium salts. Unsymmetrically substituted sulfonium salts were obtained through a similar treatment of cyanoethylthioether-undecahydro-closo-dodecaborate tetramethylammonium salt with haloalkyl carboxylic acid. Selective removal of the remaining cyanoethyl group upon treatment with tetramethylammonium hydroxide yielded S-carboxyalkyl-thioether-undecahydro-closo-dodecaborate ditetramethylammonium salts. N,N'-dicyclohexylcarbodiimide (DCC) activated amidation of S,S-bis(carboxyalkyl)sulfonium-undecahydro-closo-dodecaborate or S-carboxyalkyl-thioether-undecahydro-closo-dodecaborate tetramethylammonium salts with propargylamine provided the opportunity to install terminal acetylene groups for further conjugation. These compounds acted as powerful building blocks for the synthesis of a broad range of 1,4-disubstituted 1,2,3-triazole products in high yields, utilizing the Cu(I)-mediated click cycloaddition reaction. The synthesis of BSH-lipid with a two-tailed moiety was also achieved, by esterification of S,S-bis(carboxyethyl)sulfoniumundecahydro-closo-dodecaborate(1-) tetramethylammonium salt with 1,2-O-distearoyl-sn-3-glycerol, which may prove useful in the liposomal boron delivery system. The bio-compatibility of the azide-alkyne click reaction was then utilized by performing this reaction in cell culture. The distribution of BSH in HeLa cells could be visualized by treating the cells first with a BSH-alkyne compound and then with Alexa Fluor 488(®) azide dye. The BSH-dye conjugate, which did not wash out, revealed the distribution of boron in the He

  7. Selective boron accumulation in human ocular melanoma by 10B1-para-boronophenylalanine administration for neutron capture therapy

    International Nuclear Information System (INIS)

    Wadabayashi, Nobutoshi; Ichihashi, Masamitsu; Honda, Chihiro; Mishima, Yutaka.

    1994-01-01

    Malignant melanoma occurs not only in the skin but also in ocular tissues. Ocular melanoma located superficially as in conjunctiva can be treated successfully by BNCT. In the present study, we investigated 10 B dynamics in ocular melanoma and the surrounding normal tissues, to evaluate the possibility of applying BNCT to ocular melanoma. In three ocular melanoma patients, 10 B concentration in melanoma after administration of 10 B-BPA by oral or drip infusion ranged from 10.4 to 21.5 ppm. The boron concentrations in lens and vitreous body were lower than blood level, whereas higher than blood in sclera and palpebral skin. These results suggest that we can treat such a superficial melanoma lesions as conjunctival melanoma by BNCT using 10 B 1 -BPA. (author)

  8. A CONCEPTUAL DESIGN OF NEUTRON COLLIMATOR IN THE THERMAL COLUMN OF KARTINI RESEARCH REACTOR FOR IN VITRO AND IN VIVO TEST OF BORON NEUTRON CAPTURE THERAPY

    Directory of Open Access Journals (Sweden)

    Nina Fauziah

    2015-03-01

    Full Text Available Studies were carried out to design a collimator which results in epithermal neutron beam for IN VITRO and IN VIVO of Boron Neutron Capture Therapy (BNCT at the Kartini research reactor by means of Monte Carlo N-Particle (MCNP codes. Reactor within 100 kW of thermal power was used as the neutron source. The design criteria were based on recommendation from the International Atomic Energy Agency (IAEA. All materials used were varied in size, according to the value of mean free path for each material. MCNP simulations indicated that by using 5 cm thick of Ni as collimator wall, 60 cm thick of Al as moderator, 15 cm thick of 60Ni as filter, 2 cm thick of Bi as γ-ray shielding, 3 cm thick of 6Li2CO3-polyethylene as beam delimiter, with 1 to 5 cm varied aperture size, epithermal neutron beam with maximum flux of 7.65 x 108 n.cm-2.s-1 could be produced. The beam has minimum fast neutron and γ-ray components of, respectively, 1.76 x 10-13 Gy.cm2.n-1 and 1.32 x 10-13 Gy.cm2.n-1, minimum thermal neutron per epithermal neutron ratio of 0.008, and maximum directionality of 0.73. It did not fully pass the IAEA’s criteria, since the epithermal neutron flux was below the recommended value, 1.0 x 109 n.cm-2.s-1. Nonetheless, it was still usable with epithermal neutron flux exceeding 5.0 x 108 n.cm-2.s-1. When it was assumed that the graphite inside the thermal column was not discharged but only the part which was going to be replaced by the collimator, the performance of the collimator became better within the positive effect from the surrounding graphite that the beam resulted passed all criteria with epithermal neutron flux up to 1.68 x 109 n.cm-2.s-1. Keywords: design, collimator, epithermal neutron beam, BNCT, MCNP, criteria   Telah dilakukan penelitian tentang desain kolimator yang menghasilkan radiasi netron epitermal untuk uji in vitro dan in vivo pada Boron Neutron Capture Therapy (BNCT di Reaktor Riset Kartini dengan menggunakan program Monte

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

    Energy Technology Data Exchange (ETDEWEB)

    Pozzi, E. [Research and Production Reactors, National Atomic Energy Commission, Ezeiza Atomic Center (Argentina); Department of Radiobiology, National Atomic Energy Commission, Constituyentes Atomic Center (Argentina)], E-mail: epozzi@cnea.gov.ar; Nigg, D.W. [Idaho National Laboratory, Idaho Falls (United States); Miller, M.; Thorp, S.I. [Instrumentation and Control Department, National Atomic Energy Commission, Ezeiza Atomic Center (Argentina); Heber, E.M. [Department of Radiobiology, National Atomic Energy Commission, Constituyentes Atomic Center (Argentina); Zarza, L.; Estryk, G. [Research and Production Reactors, National Atomic Energy Commission, Ezeiza Atomic Center (Argentina); Monti Hughes, A.; Molinari, A.J.; Garabalino, M. [Department of Radiobiology, National Atomic Energy Commission, Constituyentes Atomic Center (Argentina); Itoiz, M.E. [Department of Radiobiology, National Atomic Energy Commission, Constituyentes Atomic Center (Argentina); Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires (Argentina); Aromando, R.F. [Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires (Argentina); Quintana, J. [Research and Production Reactors, National Atomic Energy Commission, Ezeiza Atomic Center (Argentina); Trivillin, V.A.; Schwint, A.E. [Department of Radiobiology, National Atomic Energy Commission, Constituyentes Atomic Center (Argentina)

    2009-07-15

    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 7.1x10{sup 9} n cm{sup -2} s{sup -1} and the fast neutron flux was 2.5x10{sup 6} n cm{sup -2} s{sup -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 {sup 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kankaanranta, Leena [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Seppaelae, Tiina; Koivunoro, Hanna [Department of Physics, University of Helsinki, Helsinki (Finland); Boneca Corporation, Helsinki (Finland); Saarilahti, Kauko [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Atula, Timo [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Collan, Juhani [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Salli, Eero; Kortesniemi, Mika [Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Uusi-Simola, Jouni [Department of Physics, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Vaelimaeki, Petteri [Department of Physics, University of Helsinki, Helsinki (Finland); Boneca Corporation, Helsinki (Finland); Maekitie, Antti [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Seppaenen, Marko [Turku PET Centre, Turku University Hospital, Turku (Finland); Minn, Heikki [Department of Oncology, Turku University Central Hospital, Turku (Finland); Revitzer, Hannu [Aalto University School of Science and Technology, Esopo (Finland); Kouri, Mauri [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Kotiluoto, Petri; Seren, Tom; Auterinen, Iiro [VTT Technical Research Centre of Finland, Espoo (Finland); Savolainen, Sauli [Department of Physics, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Joensuu, Heikki, E-mail: heikki.joensuu@hus.fi [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland)

    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

  11. Boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM), using the epithermal neutron beam at the Brookhaven National Laboratory

    International Nuclear Information System (INIS)

    Chadha, Manjeet; Capala, Jacek; Coderre, Jeffrey A.; Elowitz, Eric H.; Joel, Darrel D.; Hungyuan, B. Liu; Slatkin, Daniel N.; Chanana, Arjun D.

    1996-01-01

    Objective: BNCT is a binary treatment modality based on the nuclear reactions that occur when boron ( 10 B) is exposed to thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy of p-boronophenylalanine (BPA)-based BNCT. The objective of the Phase I/II trial was to evaluate BPA-fructose (BPA-F) as a boron delivery agent for GBM and to study the feasibility and safety of a single-fraction of BNCT. Materials and Methods: The trial design required i) a BPA-F biodistribution study performed at the time of craniotomy; and ii) BNCT within 4 weeks of the craniotomy. From September 94 to July 95, 10 patients with biopsy proven GBM were treated. All but 1 patient underwent a biodistribution study receiving IV BPA-F at the time of craniotomy. Multiple tissue samples and concurrent blood and urine samples were collected for evaluation of the boron concentration and clearance kinetics. For BNCT all patients received 250 mg/kgm of BPA-F (IV infusion over 2 hrs) followed by neutron irradiation. The blood 10 B concentration during irradiation was used to calculate the time of neutron exposure. The 3D treatment planning was done using the BNCT treatment planning software developed at the Idaho National Engineering Laboratory. The BNCT dose is expressed as the sum of the physical dose components corrected for both the RBE and the 10 B localization factor with the unit Gy-Eq. The photon-equivalent dose, where the thermal neutron fluence reaches a maximum, is the peak-dose equivalent. A single-fraction of BNCT was delivered prescribing 10.5 Gy-Eq (9 patients) and 13.8 Gy-Eq (1 patient) as the peak dose-equivalent to the normal brain. The peak dose rate was kept below 27 cGy-Eq/min. Results: Biodistribution data: The maximum blood 10 B concentration was observed at the end of the infusion and scaled as a linear function of the administered dose. The 10 B concentration in the scalp and in the GBM tissue was higher than in blood by 1.5 x and at least 3.5 x

  12. Comparison of three experimental protocols in pre clinical studies for thyroid cancer treatment using sodium butyrate in combination with boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    Perona, M; Rodriguez, C; Carpano, M; Majdalani E; Nievas, S; Olivera, M; Pisarev, M; Cabrini, R; Juvenal, G; Dagrosa A

    2012-01-01

    Background: We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated (PDTC) and undifferentiated thyroid carcinoma (UTC). However new strategies are being assayed in order to optimize its application. Histone de acetylase inhibitors (HDAC-I) like sodium butyrate (NaB), are emerging as a new class of chemotherapeutic agents which target the epigenome. Since histone hyper acetylation mediates changes in chromatin conformation, HDAC-I are involved in different epigenetically controlled activities like apoptosis, proliferation, cell differentiation, induction of cell cycle arrest and motility. The purpose of the present studies was to analyze different treatment regimens of combination of NaB and boronophenylalanine (BPA) uptake in animals bearing transplants of a human thyroid carcinoma Methods: NIH nude mice of 6-8 weeks were implanted (s.c.) with 10 6 of human follicular thyroid carcinoma cells (WRO). Three regimens were evaluated in 48 animals after 15 days when tumors had a size between 50 and 100 mm 3 . Group 1 (n=10): BPA and NaB (50 mM) via i.p. at a dose of 110 mg/kg b.w. 24 h before boron compound administration; group 2 (n=10): BPA and NaB 3.4% in the water ad libitum during a month after 15 days post-implantation; group 3 (n=10): BPA alone. In all the groups BPA was injected at a dose of 350 mg/Kg b.w. (i.p.) and the animals were sacrificed at 2 h post-administration. Boron measurements in tissues and blood were performed by ICP-OES. A control group without NaB (n=6) for each regimen was included. The tumor growth and the body weight were determined twice a week during a month. Results: The administration of NaB 3.4% during a month previous to BNCT did not modify the body weight of the mice and decreased the tumor growth compared to its control group (p<0.01). The biodistribution studies showed a tumor boron concentration of 32.6 ± 1.4 ppm for group 1 (NaB 50 mM plus BPA), of 16.9 ± 3.7 ppm

  13. Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ling-Wei, E-mail: lwwang@vghtpe.gov.tw [Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan (China); National Yang-Ming University, Taiwan (China); Chen, Yi-Wei [Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan (China); National Yang-Ming University, Taiwan (China); Ho, Ching-Yin [National Yang-Ming University, Taiwan (China); Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan (China); Hsueh Liu, Yen-Wan [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Chou, Fong-In [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China); Liu, Yuan-Hao [Nuclear Science and Engineering Department, Nanjing University of Aeronautics and Astronautics, Nanjing (China); Liu, Hong-Ming; Peir, Jinn-Jer [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China); Jiang, Shiang-Huei [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Chang, Chi-Wei [National Yang-Ming University, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Liu, Ching-Sheng [Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan (China); National Yang-Ming University, Taiwan (China); Lin, Ko-Han [Taoyuan Veterans Hospital, Taiwan (China); Wang, Shyh-Jen [National Yang-Ming University, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Chu, Pen-Yuan [National Yang-Ming University, Taiwan (China); Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan (China); Lo, Wen-Liang; Kao, Shou-Yen [National Yang-Ming University, Taiwan (China); Department of Stomatology, Taipei Veterans General Hospital, Taiwan (China); and others

    2016-05-01

    Purpose: To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. Methods and Materials: In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA–positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. Results: Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. Conclusions: Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.

  14. SU-F-T-183: Design of a Beam Shaping Assembly of a Compact DD-Based Boron Neutron Capture Therapy System

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, M; Liu, Y; Nie, L [Purdue University, West Lafayette, Indiana (United States)

    2016-06-15

    Purpose: To design a beam shaping assembly (BSA) to shape the 2.45-MeV neutrons produced by a deuterium-deuterium (DD) neutron generator and to optimize the beam output for boron neutron capture therapy of brain tumors Methods: MCNP is used for this simulation study. The simulation model consists of a neutron surface source that resembles an actual DD source and is surrounded by a BSA. The neutron source emits 2.45-MeV neutrons isotropically. The BSA is composed of a moderator, reflector, collimator and filter. Various types of materials and geometries are tested for each component to optimize the neutron output. Neutron characteristics are measured with an 2×2×2-cm{sup 3} air-equivalent cylinder at the beam exit. The ideal BSA is determined by evaluating the in-air parameters, which include epithermal neutron per source neutron, fast neutron dose per epithermal neutron, and photon dose per epithermal neutron. The parameter values are compared to those recommended by the IAEA. Results: The ideal materials for reflector and thermal neutron filter were lead and cadmium, respectively. The thickness for reflector was 43 cm and for filter was 0.5 mm. At present, the best-performing moderator has 25 cm of AlF{sub 3} and 5 cm of MgF{sub 2}. This layout creates a neutron spectrum that has a peak at approximately 10 keV and produces 1.35E-4 epithermal neutrons per source neutron per cm{sup 2}. Additional neutron characteristics, fast neutrons per epithermal neutron and photon per epithermal neutron, are still under investigation. Conclusion: Working is ongoing to optimize the final layout of the BSA. The neutron spectrum at the beam exit window of the final configuration will have the maximum number of epithermal neutrons and limited photon and fast neutron contaminations within the recommended values by IAEA. Future studies will also include phantom experiments to validate the simulation results.

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

    International Nuclear Information System (INIS)

    Farr, L.E.

    1991-01-01

    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. Biodistribution of boron after intravenous 4-dihydroxyborylphenylalanine-fructose (BPA-F) infusion in meningioma and schwannoma patients: A feasibility study for boron neutron capture therapy.

    Science.gov (United States)

    Kulvik, Martti; Kallio, Merja; Laakso, Juha; Vähätalo, Jyrki; Hermans, Raine; Järviluoma, Eija; Paetau, Anders; Rasilainen, Merja; Ruokonen, Inkeri; Seppälä, Matti; Jääskeläinen, Juha

    2015-12-01

    We studied the uptake of boron after 100 mg/kg BPA infusion in three meningioma and five schwannoma patients as a pre-BNCT feasibility study. With average tumour-to-whole blood boron concentrations of 2.5, we discuss why BNCT could, and probably should, be developed to treat severe forms of the studied tumours. However, analysing 72 tumour and 250 blood samples yielded another finding: the plasma-to-whole blood boron concentrations varied with time, suggesting that the assumed constant boron ratio of 1:1 between normal brain tissue and whole blood deserves re-assessment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Tumor development in field-cancerized tissue is inhibited by a double application of Boron neutron capture therapy (BNCT) without exceeding radio-tolerance

    International Nuclear Information System (INIS)

    Monti Hughes, Andrea; Heber, Elisa M.; Itoiz, Maria E.; Molinari, Ana J.; Garabalino, Marcela A.; Trivillin, Veronica A.; Schwint, Amanda E.; Aromando, Romina F.

    2009-01-01

    Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of a 'single' application of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-1(Na 2 10 B 10 H 10 ) or (GB-10+BPA) to treat hamster cheek pouch tumors with no normal tissue radiotoxicity. Based on these results, we developed a model of precancerous tissue in the hamster cheek pouch for long-term studies. Employing this model we evaluated the long-term potential inhibitory effect on the development of second primary tumors from precancerous tissue and eventual radiotoxicity of a single application of BNCT mediated by BPA, GB-10 or (GB-10+BPA), in the RA-6. The clinical rationale of this study was to search for a BNCT protocol that is therapeutic for tumor, not radio-toxic for the normal tissue that lies in the neutron beam path, and exerts the desired inhibitory effect on the development of second primary tumors, without exceeding the radio-tolerance of precancerous tissue, the dose limiting tissue in this case. Second primary tumors that arise in precancerous tissue (also called locoregional recurrences) are a frequent cause of therapeutic failure in head and neck tumors. Aim: Evaluate the radiotoxicity and inhibitory effect of a 'double' application of the same BNCT protocols that were proved therapeutically successful for tumor and precancerous tissue, with a long term follow up (8 months). A 'double' application of BNCT is a potentially useful strategy for the treatment of tumors, in particular the larger ones, but the cost in terms of side-effects in dose-limiting tissues might preclude its application and requires cautious evaluation. Materials and methods: We performed a double application of 1) BPA-BNCT; 2) (GB

  18. Study of a neutron producing target via the 7Li(p,n)7Be reaction near its energy threshold for BNCT (boron neutron capture therapy)

    International Nuclear Information System (INIS)

    Burlon, Alejandro; Kreiner, Andres J.; Debray, Mario E.; Stoliar, Pablo; Kesque, Jose M.; Naab, Fabian; Ozafran, Mabel J.; Schuff, Juan; Vazquez, Monica; Caraballo, Maria E.; Valda, Alejandro; Somacal, Hector; Davidson, Miguel; Davidson, Jorge

    2000-01-01

    In the framework of Accelerator Based BNCT (AB-BNCT) the 7 Li(p,n) 7 Be reaction near its energy threshold is one of the most promising. In this work a thick LiF target irradiated with a proton beam was studied as a neutron source. The 1.88-2.0 MeV proton beam was produced by the tandem accelerator TANDAR at CNEA's facilities in Buenos Aires. A water-filled phantom, containing a boron sample was irradiated with the resulting neutron beam. The boron neutron capture reaction produces a 0.478 MeV gamma ray in 94 % of the cases. The neutron yield was monitored by detecting this gamma ray using a germanium detector with an 'anti-Compton' shield. Moreover, the thermal neutron flux was evaluated at different depths inside the phantom using bare and Cd-covered gold foils. A maximum neutron thermal flux of 1.4 x 10 8 1/(cm 2 -s-mA) was obtained at 4.2 cm from the phantom surface. (author)

  19. Determination Of Natural Boron Concentration In Coffee Leaves, Using de Autobiography by Neutron Capture Technique

    International Nuclear Information System (INIS)

    Loria, L. G.; Jimenez, R.; Thellier, M.

    1999-01-01

    Determination of natural boron concentration in coffee leaves, using the autoradiography, by neutron capture technique. The boron absorption coefficient in young coffee leaves was measured using autoradiography by neutron capture. In two experiments carried out in April and November, 1996, it was found that the coefficient varies between 0.9 and 5.3 nmol/h. the concentration of natural boron in coffee leaves in regard to age, symptoms and treatment received was also studied, using the same technique. (Author) [es

  20. A feasibility study of a deuterium-deuterium neutron generator-based boron neutron capture therapy system for treatment of brain tumors.

    Science.gov (United States)

    Hsieh, Mindy; Liu, Yingzi; Mostafaei, Farshad; Poulson, Jean M; Nie, Linda H

    2017-02-01

    Boron neutron capture therapy (BNCT) is a binary treatment modality that uses high LET particles to achieve tumor cell killing. Deuterium-deuterium (DD) compact neutron generators have advantages over nuclear reactors and large accelerators as the BNCT neutron source, such as their compact size, low cost, and relatively easy installation. The purpose of this study is to design a beam shaping assembly (BSA) for a DD neutron generator and assess the potential of a DD-based BNCT system using Monte Carlo (MC) simulations. The MC model consisted of a head phantom, a DD neutron source, and a BSA. The head phantom had tally cylinders along the centerline for computing neutron and photon fluences and calculating the dose as a function of depth. The head phantom was placed at 4 cm from the BSA. The neutron source was modeled to resemble the source of our current DD neutron generator. A BSA was designed to moderate and shape the 2.45-MeV DD neutrons to the epithermal (0.5 eV to 10 keV) range. The BSA had multiple components, including moderator, reflector, collimator, and filter. Various materials and configurations were tested for each component. Each BSA layout was assessed in terms of the in-air and in-phantom parameters. The maximum brain dose was limited to 12.5 Gray-Equivalent (Gy-Eq) and the skin dose to 18 Gy-Eq. The optimized BSA configuration included 30 cm of lead for reflector, 45 cm of LiF, and 10 cm of MgF 2 for moderator, 10 cm of lead for collimator, and 0.1 mm of cadmium for thermal neutron filter. Epithermal flux at the beam aperture was 1.0 × 10 5  n epi /cm 2 -s; thermal-to-epithermal neutron ratio was 0.05; fast neutron dose per epithermal was 5.5 × 10 -13  Gy-cm 2 /φ epi , and photon dose per epithermal was 2.4 × 10 -13  Gy-cm 2 /φ epi . The AD, AR, and the advantage depth dose rate were 12.1 cm, 3.7, and 3.2 × 10 -3  cGy-Eq/min, respectively. The maximum skin dose was 0.56 Gy-Eq. The DD neutron yield that is needed to

  1. 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.

    Directory of Open Access Journals (Sweden)

    Subhash Chandra

    Full Text Available 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.

  2. Advances in neutron capture therapy 2006. Proceedings of 12th international congress on neutron capture therapy

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Kobayashi, Tooru; Fukuda, Hiroshi

    2006-01-01

    The Twelfth International Congress on Neutron Capture Therapy (ICNCT-12) is being held from October 9th to 13th, 2006 at the Kagawa International Congress Hall in Takamatsu, Kagawa, Japan. The main theme of the congress is From the past to the Future'. Five symposiums were organized to accommodate all the contributions from the international scientific committees of the International Society for Neutron Capture Therapy (ISNCT), and two symposiums were added to balance the number of fields of specialties. The seven symposiums for ICNCT-12 are as follows: 1) Clinical Results of BNCT for Brain Tumors, 2) Dosimetry, 3) Treatment Planning system, 4) Drug Delivery System, 5) Biomedical and General Matters, 6) BNCT Systems using Accelerators, 7) New Applications and Protocols for BNCT. There are a total of 195 presentations in this congress: 3 special lectures, 34 symposium presentations, 10 presentations in two special sessions from the recipients of the Ralph G. Fairchild Award, 70 presentations in the oral parallel sessions and 78 presentations in the poster sessions. A compilation of 169 papers are published in this proceedings. The 165 of the presented papers are indexed individually. (J.P.N.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Heber, Elisa M. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Hawthorne, M. Frederick [Univ. of Missouri, Columbia, MO (United States). International Inst. of Nano and Molecular Medicine; Kueffer, Peter J. [Univ. of Missouri, Columbia, MO (United States). International Inst. of Nano and Molecular Medicine; Garabalino, Marcela A. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Thorp, Silvia I. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Pozzi, Emiliano C. C. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Hughes, Andrea Monti [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Maitz, Charles A. [Univ. of Missouri, Columbia, MO (United States). International Inst. of Nano and Molecular Medicine; Jalisatgi, Satish S. [Univ. of Missouri, Columbia, MO (United States). International Inst. of Nano and Molecular Medicine; Nigg, David W. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Curotto, Paula [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Trivillin, Verónica A. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Schwint, Amanda E. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina)

    2014-11-11

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

  7. Boron neutron capture synovectomy at SINQ in Switzerland

    Energy Technology Data Exchange (ETDEWEB)

    Crompton, N.E.A.; Kuehne, G.; Crawford, J. [Paul Scherrer Institute, Villigen-PSI (Switzerland); Gay, S.; Pap, T. [Rheumatology Clinic, Zuerich (Switzerland)

    2000-10-01

    One percent of the Swiss population suffers from the crippling disease rheumatoid arthritis (RA) of the hand with associated inflammation of various finger joints. Loss of manual dexterity results in a greatly reduced quality of life, especially in the elderly. Current medical treatment of pharmaceutically unresponsive RA involves either surgery or application of the {beta}-emitters: Yttrium or Erbium. However, both procedures have disadvantages. The small size of the finger joints makes surgery impractical and is therefore not practiced in Switzerland. However, application of Yttrium or Erbium presents a radiation protection problem because the arthritic joint has the potential to leak. For this reason application of {beta}-emitters for RA does not have FDA approval in the US. A promising alternative has recently been under investigation at MIT: Neutron Capture Synovectomy (NCS). Treatment of the arthritic human hand, in particular the metacarpopharangeal and proximal interpharangeal finger joints, involves prior injection of an enriched Boron-10 compound and subsequent irradiation with thermal neutrons. This method avoids the drawbacks of the existing treatments. Introduction of NCS to the SINQ will require preclinical studies to establish the treatment conditions necessary and the effectivity of the planned treatment (Phase 0). The studies will include neutron exposures of cell cultures and joint samples at the new neutron capture radiography facility (NCR) on the cold neutron guide 13. Introduction of NCS will also require construction of a suitable treatment facility for human patients at Sektor 80 of SINQ. Prerequisites which ensure comfortable and expedient treatment of the patient and exposure conditions respecting the demands of radiation protection regulations and the complete safety of the patient must be fulfilled in the construction of the NCS treatment facility. A temporary construction is envisaged for the early clinical trials (Phase I). A more

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

    International Nuclear Information System (INIS)

    Nigg, David Waler

    2003-01-01

    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

  9. Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion.

    Science.gov (United States)

    Yanagie, Hironobu; Kumada, Hiroaki; Nakamura, Takemi; Higashi, Syushi; Ikushima, Ichiro; Morishita, Yasuyuki; Shinohara, Atsuko; Fijihara, Mitsuteru; Suzuki, Minoru; Sakurai, Yoshinori; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Nishimura, Ryohei; Ono, Koji; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Takahashi, Hiroyuki

    2011-12-01

    Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of (10)B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared (10)BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), (10)BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients. WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient. The (10)B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that (10)B entrapped WOW emulsion could be applied to novel intra-arterial boron delivery carrier

  10. Designing an Epithermal Neutron Beam for Boron Neutron Capture Therapy for the Fusion Reactions 2H(d,n)3He and 3H(d,n)4He1

    International Nuclear Information System (INIS)

    Verbeke, J.M.; Costes, S.V.; Bleuel, D.; Vujic, J.; Leung, K.N.

    1998-01-01

    A beam shaping assembly has been designed to moderate high energy neutrons from the fusion reactions 2 H(d,N) 3 He and 3 H(d,n) 4 He for use fin boron neutron capture therapy. The low neutron yield of the 2 H(d,n) 3 He reaction led to unacceptably long treatment times. However, a 160 mA deuteron beam of energy 400 keV led to a treatment time of 120 minutes with the reaction 3 H(d,n) 4 He. Equivalent doses of 9.6 Gy-Eq and 21.9 Gy-Eq to the skin and to a 8 cm deep tumor respectively have been computed

  11. Carboranyl Oligonucleotides for Neutron Capture Therapy Final Report

    International Nuclear Information System (INIS)

    Schinazi, Raymond F.

    2004-01-01

    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-(β-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

  12. Neutron-photon mixed field dosimetry by TLD-700 glow curve analysis and its implementation in dose monitoring for Boron Neutron Capture Therapy (BNCT) treatments

    Energy Technology Data Exchange (ETDEWEB)

    Boggio, E. F.; Longhino, J. M. [Centro Atomico Bariloche, Departamento de Fisica de Reactores y Radiaciones / CNEA, Av. E. Bustillo Km 9.5, R8402AGP San Carlos de Bariloche (Argentina); Andres, P. A., E-mail: efboggio@cab.cnea.gov.ar [Centro Atomico Bariloche, Division Proteccion Radiologica / CNEA, Av. E. Bustillo Km 9.5, R8402AGP San Carlos de Bariloche (Argentina)

    2015-10-15

    BNCT is a cancerous cells selective, non-conventional radiotherapy modality to treat malignant tumors such as glioblastoma, melanoma and recurrent head and neck cancer. It consists of a two-step procedure: first, the patient is injected with a tumor localizing drug containing a non-radioactive isotope (Boron-10) with high slow neutron capture cross-section. In a second step, the patient is irradiated with neutrons, which are absorbed by the Boron-10 agent with the subsequently nuclear reaction B- 10(n,a)Li-7, thereby resulting in dose at cellular level due to the high-Let particles. The neutron fields suitable for BNCT are characterized by high neutron fluxes and low gamma dose. Determination of each component is not an easy task, especially when the volume of measurement is quite small or inaccessible for a miniature ionization chamber, for example. A method of measuring the photon and slow neutron dose(mainly by N-14 and B-10) from the glow curve (GC) analysis of a single {sup 7}LiF thermoluminescence detector is evaluated. This method was suggested by the group headed by Dr. Grazia Gambarini. The dosemeters used were TLD-600 ({sup 6}LiF:Mg,Ti with 95.6% {sup 6}Li) and TLD-700 ({sup 7}LiF:Mg,Ti with 99.9% {sup 7}LiF) from Harshaw. Photon dose measurement using the GC analysis method with TLD-700 in mixed fields requires the relation of the two main peaks of a TLD-600 GC shape obtained from an exposition to the same neutron field, and a photon calibrated GC with TLD-700. The requirements for slow neutron dose measurements are similar. In order to properly apply the GC analysis method at the Ra-6 Research Reactor BNCT facility, measurements were carried out in a standard water phantom, fully characterized on the BNCT beam by conventional techniques (activation detectors and paired ionization chambers technique). Next, the method was implemented in whole body dose monitoring of a patient undergoing a BNCT treatment, using a Bo MAb (Bottle Manikin Absorption) phantom

  13. Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion

    International Nuclear Information System (INIS)

    Yanagie, Hironobu; Kumada, Hiroaki; Nakamura, Takemi; Higashi, Syushi; Ikushima, Ichiro; Morishita, Yasuyuki; Shinohara, Atsuko; Fijihara, Mitsuteru; Suzuki, Minoru; Sakurai, Yoshinori; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Nishimura, Ryohei; Ono, Koji; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Takahashi, Hiroyuki

    2011-01-01

    Introduction: Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10 B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of 10 B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared 10 BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), 10 BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients. Materials and methods: WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient. Results and discussions: The 10 B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that 10 B entrapped WOW emulsion could be

  14. Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Yanagie, Hironobu, E-mail: yanagie@n.t.u-tokyo.ac.jp [Dept of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)] [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Kumada, Hiroaki [Proton Medical Research Center, University of Tsukuba, Ibaraki (Japan); Nakamura, Takemi [Japan Atomic Energy Research Institute, Ibaraki (Japan); Higashi, Syushi [Dept of Surgery, Ebihara Memorial Hospital, Miyazaki (Japan)] [Kyushu Industrial Sources Foundation, Miyazaki (Japan); Ikushima, Ichiro [Dept of Radiology, Miyakonojyo Metropolitan Hospital, Miyazaki (Japan); Morishita, Yasuyuki [Dept of Human and Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo (Japan); Shinohara, Atsuko [Dept of Humanities, Graduate School of Seisen University, Tokyo (Japan); Fijihara, Mitsuteru [SPG Techno Ltd. Co., Miyazaki (Japan); Suzuki, Minoru; Sakurai, Yoshinori [Research Reactor Institute, Kyoto University, Osaka (Japan); Sugiyama, Hirotaka [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Kajiyama, Tetsuya [Kyushu Industrial Sources Foundation, Miyazaki (Japan); Nishimura, Ryohei [Dept of Veternary Surgery, University of Tokyo Veternary Hospital, Tokyo (Japan); Ono, Koji [Research Reactor Institute, Kyoto University, Osaka (Japan); Nakajima, Jun; Ono, Minoru [Dept of Cardiothracic Surgery, University of Tokyo Hospital, Tokyo (Japan); Eriguchi, Masazumi [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)] [Department of Surgery, Shin-Yamanote Hospital, Saitama (Japan); Takahashi, Hiroyuki [Dept of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)] [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)

    2011-12-15

    Introduction: Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between {sup 10}B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of {sup 10}B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared {sup 10}BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), {sup 10}BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients. Materials and methods: WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient. Results and discussions: The {sup 10}B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that {sup 10}B

  15. Irradiation system for neutron capture therapy using the small accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Tooru [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.; Tanaka, Kenichi [Kyoto Univ. (Japan). Graduate School of Engineering; Nakagawa, Yoshinobu [Kagawa Children' s Hospital, Zentsuji (Japan); Hoshi, Masaharu [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

    2002-09-01

    Neutron capture therapy (NCT) is to kill tumor cells that previously incorporated the stable isotope which generates heavy charged particles with a short range and a high linear energy transfer (LET) on neutron irradiation. Boron-10 is ordinarily used as such an isotope. The tumor tissue is neutron-irradiated at craniotomy after preceding craniotomy for tumor extraction: therefore two surgeries are required for the present NCT in Japan. The reactions {sup 10}B(n, {alpha}{gamma}) {sup 7}Li and {sup 7}Li (p, n) {sup 7}Be are thought preferential for patients and doctors if a convenient small accelerator, not the reactor used at present, is available in the hospital because only one craniotomy is sufficient. Authors' examinations of the system for NCT using the small accelerator involve irradiation conditions, desirable energy spectrum of neutron, characterization of thermal and epi-thermal neutrons, social, practical and technical comparison of the reactor and accelerator, and usefulness of the reaction {sup 7}Li (p, n) {sup 7}Be. The system devoted to the NCT is awaited in future. (K.H.)

  16. License amendment for neutron capture therapy at the MIT research reactor

    International Nuclear Information System (INIS)

    Bernard, J.A.

    1993-01-01

    This paper reports the issuance by the U.S. Nuclear Regulatory Commission (NRC) of a license amendment to the Massachusetts Institute of Technology (MIT) for the use of the MIT Research Reactor's (MITR-II) medical therapy facility beam for the treatment of humans using neutron capture therapy (NCT). This amendment is one of 11 required approvals. The others are those of internal MIT committees, review panels of the Tufts-New England Medical Center (NEMC), which is directing the program jointly with MIT, that of the U.S. Food and Drug Administration, and an NRC amendment to the NEMC hospital license. This amendment is the first of its type to be issued by NRC, and as such it establishes a precedent for the conduct of human therapy using neutron beams. Neutron capture therapy is a bimodal method for treating cancer that entails the administration of a tumor-seeking boronated drug followed by the irradiation of the target organ with neutrons. The latter cause boron nuclei to fission and thereby release densely ionizing helium and lithium nuclei, which destroy cancerous cells while leaving adjacent healthy cells undamaged. Neutron capture therapy is applicable to glioblastoma multiforme (brain tumors) and metastasized melanoma (skin cancer). Both Brookhaven National Laboratory and MIT conducted trials of NCT more than 30 yr ago. These were unsuccessful because the available boron drugs did not concentrate sufficiently in tumor and because the thermal neutron beams that were used did not enable neutrons to travel deep enough into the brain

  17. Molecular medicine: Synthesis and in-vivo detection of agents for use in boron neutron capture therapy. Final report, May 1, 1993--April 30, 1996

    International Nuclear Information System (INIS)

    Kabalka, G.W.

    1997-08-01

    During the early stages of this project, the author developed the first whole-body boron MRI technique. They found that, for the first time, information concerning both the location and the quantity of boron present in living tissues could be obtained through the use of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) respectively. However, it was also discovered that boron MRI was not without problems. Both naturally occurring isotopes of boron (boron-10 and boron-11) possess magnetic moments, making them amenable to MR detection. The author found that there are difficulties in obtaining boron MRI images which are a consequence of the inherently poor magnetic resonance characteristics of the boron nucleus. The magnetogyric ratios of both boron-10 and boron-11 are smaller than those of hydrogen, which makes boron much less sensitive to magnetic resonance detection. In addition, both isotopes of boron posses nuclear electric quadrupole moments which serve to shorten their magnetization relaxation times; this causes the MR signal to broaden and decay rapidly, often before the receiver coils can collect the MR information. The rapid rate of signal decay is enhanced in biological systems which leads to further signal loss and a decrease in the signal to noise ratio (SNR)

  18. Molecular medicine: Synthesis and in-vivo detection of agents for use in boron neutron capture therapy. Final report, May 1, 1993--April 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Kabalka, G.W.

    1997-08-01

    During the early stages of this project, the author developed the first whole-body boron MRI technique. They found that, for the first time, information concerning both the location and the quantity of boron present in living tissues could be obtained through the use of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) respectively. However, it was also discovered that boron MRI was not without problems. Both naturally occurring isotopes of boron (boron-10 and boron-11) possess magnetic moments, making them amenable to MR detection. The author found that there are difficulties in obtaining boron MRI images which are a consequence of the inherently poor magnetic resonance characteristics of the boron nucleus. The magnetogyric ratios of both boron-10 and boron-11 are smaller than those of hydrogen, which makes boron much less sensitive to magnetic resonance detection. In addition, both isotopes of boron posses nuclear electric quadrupole moments which serve to shorten their magnetization relaxation times; this causes the MR signal to broaden and decay rapidly, often before the receiver coils can collect the MR information. The rapid rate of signal decay is enhanced in biological systems which leads to further signal loss and a decrease in the signal to noise ratio (SNR).

  19. A novel 10B-enriched carboranyl-containing phthalocyanine as a radio- and photo-sensitising agent for boron neutron capture therapy and photodynamic therapy of tumours: in vitro and in vivo studies.

    Science.gov (United States)

    Friso, Elisabetta; Roncucci, Gabrio; Dei, Donata; Soncin, Marina; Fabris, Clara; Chiti, Giacomo; Colautti, Paolo; Esposito, Juan; De Nardo, Laura; Riccardo Rossi, Carlo; Nitti, Donato; Giuntini, Francesca; Borsetto, Lara; Jori, Giulio

    2006-01-01

    The synthesis of a Zn(ii)-phthalocyanine derivative bearing four 10B-enriched o-carboranyl units (10B-ZnB4Pc) and its natural isotopic abundance analogue (ZnB4Pc) in the peripheral positions of the tetraazaisoindole macrocycle is presented. The photophysical properties of ZnB4Pc, as tested against model biological systems, were found to be similar with those typical of other photodynamically active porphyrin-type photosensitisers, including a singlet oxygen quantum yield of 0.67. The carboranyl-carrying phthalocyanine was efficiently accumulated by B16F1 melanotic melanoma cells in vitro, appeared to be partitioned in at least some subcellular organelles and, upon red light irradiation, induced extensive cell mortality. Moreover, ZnB4Pc, once i.v.-injected to C57BL/6 mice bearing a subcutaneously transplanted pigmented melanoma, photosensitised an important tumour response, provided that the irradiation at 600-700 nm was performed 3 h after the phthalocyanine administration, when appreciable concentrations of ZnB4Pc were still present in the serum. Analogously, irradiation of the 10B-ZnB4Pc-loaded pigmented melanoma with thermal neutrons 24 h after injection led to a 4 day delay in tumour growth as compared with control untreated mice. These results open the possibility to use one chemical compound as both a photosensitising and a radiosensitising agent for the treatment of tumours by the combined application of photodynamic therapy and boron neutron capture therapy.

  20. Treatment of malignant brain tumors using nuclear reactor. Neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Akira; Yamamoto, Tetsuya; Shibata, Yasushi; Nose, Tadao [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Yamamoto, Kazuyoshi; Kumada, Hiroaki; Torii, Yoshinari [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2001-10-01

    Principles, history, clinical trial experiences and future view of the neutron capture therapy are described. The therapy using {sup 10}B (boron neutron capture therapy, BNCT) involves the intravenous injection of {sup 10}B-containing compound to be accumulated in the tumor and following irradiation of thermal (<0.53 eV, for tumors near surface) or epithermal (in depth) neutron to the target. Alpha-ray (2.34 MeV, range about 10 {mu}m) generated by neutron capture of the boron isotope is efficient to give high dose lethal effects on tumor cells with scarce affection on the normal brain cells. BNCT has been conducted from 1951 (firstly at Brookhaven National Laboratory) in the United States and in Japan, from 1968 (firstly, using Hitachi HiTR reactor). Thereafter, JRR-3, KUR, KUR-M, MulTR, JRR-2 and JRR-4 have been used for 246 patients in total. In Japan, irradiation is performed to the exposed tumor following craniotomy and dose escalation study is in progress. This clinical trial, Phase I/II study, uses the thermal neutron mode I (mixed neutron beam) from JRR-4 and 4 glioblastoma and 3 glioma patients have received the therapy with satisfactory results. Development of better {sup 10}B-containing compound, of multi-gated and boost irradiation, of accelerator exclusively for the therapy and of systemic facility for the therapy are waited. (K.H.)

  1. Predicted performance of a PG-SPECT system using CZT primary detectors and secondary Compton-suppression anti-coincidence detectors under near-clinical settings for boron neutron capture therapy

    Science.gov (United States)

    Hales, Brian; Katabuchi, Tatsuya; Igashira, Masayuki; Terada, Kazushi; Hayashizaki, Noriyosu; Kobayashi, Tooru

    2017-12-01

    A test version of a prompt-gamma single photon emission computed tomography (PG-SPECT) system for boron neutron capture therapy (BNCT) using a CdZnTe (CZT) semiconductor detector with a secondary BGO anti-Compton suppression detector has been designed. A phantom with healthy tissue region of pure water, and 2 tumor regions of 5 wt% borated polyethylene was irradiated to a fluence of 1.3 × 109 n/cm2. The number of 478 keV foreground, background, and net counts were measured for each detector position and angle. Using only experimentally measured net counts, an image of the 478 keV production from the 10B(n , α) 7Li* reaction was reconstructed. Using Monte Carlo simulation and the experimentally measured background counts, the reliability of the system under clinically accurate parameters was extrapolated. After extrapolation, it was found that the value of the maximum-value pixel in the reconstructed 478 keV γ-ray production image overestimates the simulated production by an average of 9.2%, and that the standard deviation associated with the same value is 11.4%.

  2. Dynamic changes in18F-borono-L-phenylalanine uptake in unresectable, advanced, or recurrent squamous cell carcinoma of the head and neck and malignant melanoma during boron neutron capture therapy patient selection.

    Science.gov (United States)

    Morita, Takahiro; Kurihara, Hiroaki; Hiroi, Kenta; Honda, Natsuki; Igaki, Hiroshi; Hatazawa, Jun; Arai, Yasuaki; Itami, Jun

    2018-01-11

    We evaluated dynamic changes in 18 F-borono-L-phenylalanine ( 18 F-BPA) uptake in unresectable, advanced, or recurrent squamous cell carcinoma of the head and neck (SCC) and malignant melanoma (MM) during boron neutron capture therapy (BNCT) patient selection. Dynamic changes in the maximum standardized uptake value (SUVmax), tumor-to-normal tissue ratio (TNR), and tumor-to-blood pool ratio (TBR) for 18 F-BPA were evaluated in 20 patients with SCC and 8 patients with MM. SUVmax in SCC tumors decreased significantly from 30 to 120 min. There was a non-statistically significant decrease in SUVmax for SCC tumors from 30 to 60 min and from 60 to 120 min. Patients with MM had nonsignificant SUVmax changes in 18 F-BPA uptake on delayed imaging. Nonsignificant 18 F-BPA TNR and TBR changes were seen in patients with SCC and MM. Dynamic changes in SUVmax for 18 F-BPA uptake had a washout pattern in SCC and a persistent pattern in MM. Dynamic 18 F-BPA -PET studies should be performed to investigate the pharmacokinetics of 18 F-BPA in humans and select appropriate candidates who may benefit from BNCT.

  3. 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

    Energy Technology Data Exchange (ETDEWEB)

    Sakurai, Yoshinori [Kyoto University Research Reactor Institute, Asashironishi 2-1010, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan); Ono, Koji [Kyoto University Research Reactor Institute, Asashironishi 2-1010, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan); Miyatake, Shin-ichi [Department of Neurosurgery, Osaka Medical College, Daigaku-cho 2-7, Takatsuki City, Osaka 569-8686 (Japan); Maruhashi, Akira [Kyoto University Research Reactor Institute, Asashironishi 2-1010, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan)

    2006-03-07

    Boron neutron capture therapy (BNCT) without craniotomy for malignant brain tumours was started using an epi-thermal neutron beam at the Kyoto University Reactor in June 2002. We have tried some techniques to overcome the treatable-depth limit in BNCT. One of the effective techniques is void formation utilizing a tumour-removed cavity. The tumorous part is removed by craniotomy about 1 week before a BNCT treatment in our protocol. Just before the BNCT irradiation, the cerebro-spinal fluid (CSF) in the tumour-removed cavity is drained out, air is infused to the cavity and then the void is made. This void improves the neutron penetration, and the thermal neutron flux at depth increases. The phantom experiments and survey simulations modelling the CSF drainage and air infusion of the tumour-removed cavity were performed for the size and shape of the void. The advantage of the CSF drainage and air infusion is confirmed for the improvement in the depth-dose distribution. From the parametric surveys, it was confirmed that the cavity volume had good correlation with the improvement effect, and the larger effect was expected as the cavity volume was larger.

  4. Evaluation of radioactivity in the bodies of mice induced by neutron exposure from an epi-thermal neutron source of an accelerator-based boron neutron capture therapy system

    Science.gov (United States)

    NAKAMURA, Satoshi; IMAMICHI, Shoji; MASUMOTO, Kazuyoshi; ITO, Masashi; WAKITA, Akihisa; OKAMOTO, Hiroyuki; NISHIOKA, Shie; IIJIMA, Kotaro; KOBAYASHI, Kazuma; ABE, Yoshihisa; IGAKI, Hiroshi; KURITA, Kazuyoshi; NISHIO, Teiji; MASUTANI, Mitsuko; ITAMI, Jun

    2017-01-01

    This study aimed to evaluate the residual radioactivity in mice induced by neutron irradiation with an accelerator-based boron neutron capture therapy (BNCT) system using a solid Li target. The radionuclides and their activities were evaluated using a high-purity germanium (HP-Ge) detector. The saturated radioactivity of the irradiated mouse was estimated to assess the radiation protection needs for using the accelerator-based BNCT system. 24Na, 38Cl, 80mBr, 82Br, 56Mn, and 42K were identified, and their saturated radioactivities were (1.4 ± 0.1) × 102, (2.2 ± 0.1) × 101, (3.4 ± 0.4) × 102, 2.8 ± 0.1, 8.0 ± 0.1, and (3.8 ± 0.1) × 101 Bq/g/mA, respectively. The 24Na activation rate at a given neutron fluence was found to be consistent with the value reported from nuclear-reactor-based BNCT experiments. The induced activity of each nuclide can be estimated by entering the saturated activity of each nuclide, sample mass, irradiation time, and proton current into the derived activation equation in our accelerator-based BNCT system. PMID:29225308

  5. Synthesis of PBAD-lipiodol nanoparticles for combination treatment with boric acid in boron neutron capture therapy for hepatoma in-vitro

    International Nuclear Information System (INIS)

    Chou, F.I.; Chung, H.P.; Liu, H.M.; Wen, H.W.; Chi, C.W.; Lin, Shanyang; Lui, W.Y.; Kai, J.J.

    2006-01-01

    This study attempted to increase BNCT efficiency for hepatoma by a combined treatment of phenylboric acid derivative entrapped lipiodol nanoparticles (PBAD-L nanoparticles) with boric acid. The size of PBAD-L nanoparticles were 400-750 nm at the boron concentrations of 0.3-2.7 mg/ml. After 24 hours the boron concentration in PBAD-L nanoparticles treated human hepatoma HepG2 cells was 112 ppm, while that in rat liver Clone 9 cells was 52 ppm. With the use of 25 μg B/ml boric acid, after 6 hours the boron concentration in HepG2 and Clone 9 cells were 75 ppm and 40 ppm, respectively. In a combined treatment, boron concentration in HepG2 cells which were treated with PBAD-L nanoparticles for 18 hours and then combined with boric acid for 6 hours was 158 ppm. After neutron irradiation, the surviving fraction of HepG2 cells treated with PBAD-L nanoparticles was 12.6%, while that in the ones with a combined treatment was 1.3%. In conclusion, the combined treatment provided a higher boron concentration in HepG2 cells than treatments with either PBAD-L nanoparticles or boric acid, resulting in a higher therapeutic efficacy of BNCT in hepatoma cells. (author)

  6. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Tumor control induced by Boron Neutron Capture Therapy (BNCT) as a function of dose in an experimental model of liver metastases at 5 weeks follow-up

    International Nuclear Information System (INIS)

    Pozzi, E C C; Trivillin, V A; Colombo, L L; Monti Hughes, A; Thorp, S; Cardoso, J E; Garabalino, M A; Molinari, A J; Heber, E M; Curotto, Paula; Miller, M; Itoiz, M E; Aromando, R F; Nigg, D W; Schwint, A E

    2012-01-01

    BNCT has been proposed for the treatment of multifocal, non-resectable, bilobar colorectal liver metastases that do not respond to chemotherapy. We recently reported that BNCT mediated by boronophenylalanine (BPA) induced significant remission of experimental colorectal tumor nodules in rat liver at 3 weeks follow-up with no contributory liver toxicity (Pozzi et al.,2012). The aim of the present study was to evaluate tumor control and potential liver toxicity of BPA-BNCT at 5 weeks follow-up. Prescribed dose was retrospectively evaluated based on blood boron values, allowing for assessment of response over a range of delivered dose values (author)

  8. Initiation of a phase-I trial of neutron capture therapy at the MIT research reactor

    International Nuclear Information System (INIS)

    Harling, O.K.; Bernard, J.A.; Yam, Chun-Shan

    1995-01-01

    The Massachusetts Institute of Technology (MIT), the New England Medical Center (NEMC), and Boston University Medical Center (BUMC) initiated a phase-1 trial of boron neutron capture therapy (BNCT) on September 6, 1994, at the 5-MW(thermal) MIT research reactor (MITR). A novel form of experimental cancer therapy, BNCT is being developed for certain types of highly malignant brain tumors such as glioblastoma and melanoma. The results of the phase-1 trials on patients with tumors in the legs or feet are described

  9. Neutron capture therapy of epidermal growth factor receptor (EGFR)vIII positive gliomas using boronated monoclonal antibody L8A4

    International Nuclear Information System (INIS)

    Yang, Weilian; Barth, Rolf F.; Wu, Gong

    2006-01-01

    The purpose of the present study was to evaluate the EGFRvIII specific monoclonal antibody, L8A4 as a boron delivery agent for NCT of the receptor (+) rat glioma, F98 npEGFRvIII . A heavily boronated polyamidoamine (PAMAM) dendrimer (BD) was linked to L8A4 by means of heterobifunctional reagents. Wild type (F98 WT ) receptor(-) or EGFRvIII human gene transfected receptor(+) F98 npEGFRvIII glioma cells were implanted into the brains of Fischer rats. Biodistribution studies were initiated 14 d later. Animals received 125 I-labeled BD-L8A4 by either convection enhanced delivery (CED) or intratumoral(i.t.) injection and were euthanized 6, 12, 24 or 48 h later. At 6 h following CED, equivalent amounts of the bioconjugate were detected in receptor(+) and (-) tumors, but by 24 h the amounts retained by receptor(+) gliomas were 60.1% following CED and 43.7% following i.t. injection, compared to 14.6% ID/g by receptor(-) tumors. Tumor boron concentrations were 32.7 and 44.5 μg/g, respectively, for BD-L8A4 alone or in combination with i.v. BPA. BNCT was carried out at the MITR-II Reactor 24 h after CED of BD-L8A4 (∼40 μg 10 B/∼750 μg protein) and 2.5 h after i.v. injection of BPA (500 mg/kg). Rats that received BD-L8A4 alone or in combination with BPA had mean survival times of 70.4 and 85d, respectively, with 20% and 10% long term survivors, respectively, compared to 40.1 d for i.v. BPA and 30.3 and 26.3 d for irradiated and untreated controls, respectively. These data convincingly demonstrate the therapeutic efficacy of molecular targeting of EGFRvIII and should provide a platform for the future development of combinations of high and low molecular weight delivery agents for BNCT of brain tumors. (author)

  10. 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.

    Science.gov (United States)

    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. © 2013 Elsevier Ltd. All rights reserved.

  11. Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new ''B2'' configuration of the RA-6 nuclear reactor

    Energy Technology Data Exchange (ETDEWEB)

    Monti Hughes, Andrea; Trivillin, Veronica A.; Schwint, Amanda E. [Constituyentes Atomic Center, National Atomic Energy Commission (CNEA), Department of Radiobiology, San Martin, Province Buenos Aires (Argentina); National Research Council (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Longhino, Juan; Boggio, Esteban [Bariloche Atomic Center, CNEA, Department of Nuclear Engineering, San Carlos de Bariloche, Province Rio Negro (Argentina); Medina, Vanina A.; Martinel Lamas, Diego J. [National Research Council (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Pontifical Catholic University of Argentina (UCA), Laboratory of Tumoral Biology and Inflammation, School of Medical Sciences, Institute for Biomedical Research (BIOMED CONICET-UCA), Ciudad Autonoma de Buenos Aires (Argentina); Garabalino, Marcela A.; Heber, Elisa M.; Pozzi, Emiliano C.C. [Constituyentes Atomic Center, National Atomic Energy Commission (CNEA), Department of Radiobiology, San Martin, Province Buenos Aires (Argentina); Itoiz, Maria E. [Constituyentes Atomic Center, National Atomic Energy Commission (CNEA), Department of Radiobiology, San Martin, Province Buenos Aires (Argentina); UBA, Department of Oral Pathology, Faculty of Dentistry, Ciudad Autonoma de Buenos Aires (Argentina); Aromando, Romina F. [UBA, Department of Oral Pathology, Faculty of Dentistry, Ciudad Autonoma de Buenos Aires (Argentina); Nigg, David W. [Idaho National Laboratory, Idaho Falls (United States)

    2017-11-15

    Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new ''B2'' configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in ''B1'' experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the ''B1'' results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control. (orig.)

  12. Cellular uptake and in vitro antitumor efficacy of composite liposomes for neutron capture therapy.

    Science.gov (United States)

    Peters, Tanja; Grunewald, Catrin; Blaickner, Matthias; Ziegner, Markus; Schütz, Christian; Iffland, Dorothee; Hampel, Gabriele; Nawroth, Thomas; Langguth, Peter

    2015-02-22

    Neutron capture therapy for glioblastoma has focused mainly on the use of (10)B as neutron capture isotope. However, (157)Gd offers several advantages over boron, such as higher cross section for thermal neutrons and the possibility to perform magnetic resonance imaging during neutron irradiation, thereby combining therapy and diagnostics. We have developed different liposomal formulations of gadolinium-DTPA (Magnevist®) for application in neutron capture therapy of glioblastoma. The formulations were characterized physicochemically and tested in vitro in a glioma cell model for their effectiveness. Liposomes entrapping gadolinium-DTPA as neutron capture agent were manufactured via lipid/film-extrusion method and characterized with regard to size, entrapment efficiency and in vitro release. For neutron irradiation, F98 and LN229 glioma cells were incubated with the newly developed liposomes and subsequently irradiated at the thermal column of the TRIGA reactor in Mainz. The dose rate derived from neutron irradiation with (157)Gd as neutron capturing agent was calculated via Monte Carlo simulations and set in relation to the respective cell survival. The liposomal Gd-DTPA reduced cell survival of F98 and LN229 cells significantly. Differences in liposomal composition of the formulations led to distinctly different outcome in cell survival. The amount of cellular Gd was not at all times proportional to cell survival, indicating that intracellular deposition of formulated Gd has a major influence on cell survival. The majority of the dose contribution arises from photon cross irradiation compared to a very small Gd-related dose. Liposomal gadolinium formulations represent a promising approach for neutron capture therapy of glioblastoma cells. The liposome composition determines the uptake and the survival of cells following radiation, presumably due to different uptake pathways of liposomes and intracellular deposition of gadolinium-DTPA. Due to the small range of

  13. T cell uptake for the use of boron neutron capture as an immunologic research tool

    Energy Technology Data Exchange (ETDEWEB)

    Binello, E. E-mail: ebinello@mit.edu; Mitchell, R.N.; Harling, O.K

    2004-11-01

    An immunologic tool based on manipulation of the boron neutron capture reaction was previously proposed in the context of heart transplantation research to examine the temporal relationship between parenchymal rejection (representing immune cell infiltration) and transplantation-associated arteriosclerosis (characterized by progressive vascular occlusion). Critical to the development of this method is the uptake of boron by specific cells of the immune system, namely T cells, without adverse effects on cell function, which may be assessed by the ability of boron-loaded cells to produce IFN{gamma}, a protein with substantial impact on rejection. This work presents the evaluation of two carboranyl thymidine analogs. Advantages of this type of boron compound are reduced risk of leakage and effective dose delivery based on their incorporation into cellular nuclear material. Results indicate that uptake of these boronated nucleosides is high with no adverse effects on cell function, thereby warranting the continued development of this technique that has potentially wide applicability in immunological models.

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

    International Nuclear Information System (INIS)

    Jung, J; Yoon, D; Suh, T; Hong, K

    2014-01-01

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

  15. Dose response of the AIA rabbit stifle joint to boron neutron capture synovectomy

    Energy Technology Data Exchange (ETDEWEB)

    Shortkroff, Sonya E-mail: sshortkroff@rics.bwh.harvard.edu; Binello, Emanuela; Zhu Xuping; Gierga, David; Thornhill, Thomas S.; Shefer, Ruth E.; Jones, Alun G.; Yanch, Jacquelyn C

    2004-07-01

    This study assessed the treatment with boron neutron capture synovectomy of synovitis in the antigen-induced arthritis (AIA) model. A boron compound, potassium dodecahydrododeca-borate (K{sub 2}B{sub 12}H{sub 12}), was injected into stifle joints of 24 AIA and 12 normal rabbits and activated by neutron bombardment of the joint to achieve doses from 800 to 81,000 RBE-cGy. Synovial ablation in the AIA joint was accomplished at doses of 6,000 to 7,000 RBE-cGy with no adverse effects to skin or extracapsular tissues.

  16. Neutron capture therapy beams at the MIT Research Reactor

    International Nuclear Information System (INIS)

    Choi, J.R.; Clement, S.D.; Harling, O.K.; Zamenhof, R.G.

    1990-01-01

    Several neutron beams that could be used for neutron capture therapy at MITR-II are dosimetrically characterized and their suitability for the treatment of glioblastoma multiforme and other types of tumors are described. The types of neutron beams studied are: (1) those filtered by various thicknesses of cadmium, D2O, 6Li, and bismuth; and (2) epithermal beams achieved by filtration with aluminum, sulfur, cadmium, 6Li, and bismuth. Measured dose vs. depth data are presented in polyethylene phantom with references to what can be expected in brain. The results indicate that both types of neutron beams are useful for neutron capture therapy. The first type of neutron beams have good therapeutic advantage depths (approximately 5 cm) and excellent in-phantom ratios of therapeutic dose to background dose. Such beams would be useful for treating tumors located at relatively shallow depths in the brain. On the other hand, the second type of neutron beams have superior therapeutic advantage depths (greater than 6 cm) and good in-phantom therapeutic advantage ratios. Such beams, when used along with bilateral irradiation schemes, would be able to treat tumors at any depth in the brain. Numerical examples of what could be achieved with these beams, using RBEs, fractionated-dose delivery, unilateral, and bilateral irradiation are presented in the paper. Finally, additional plans for further neutron beam development at MITR-II are discussed

  17. Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer

    Science.gov (United States)

    González, S. J.; Pozzi, E. C. C.; Monti Hughes, A.; Provenzano, L.; Koivunoro, H.; Carando, D. G.; Thorp, S. I.; Casal, M. R.; Bortolussi, S.; Trivillin, V. A.; Garabalino, M. A.; Curotto, P.; Heber, E. M.; Santa Cruz, G. A.; Kankaanranta, L.; Joensuu, H.; Schwint, A. E.

    2017-10-01

    Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson’s correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed

  18. Tratamiento del cáncer por captura neutrónica de boro: Su aplicación al carcinoma indiferenciado de tiroides Boron neutron capture therapy applied to undifferentiated thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Mario A. Pisarev

    2006-12-01

    Full Text Available El cáncer indiferenciado de tiroides es un tumor muy agresivo, de muy mal pronóstico y sin tratamiento efectivo. La terapia por captura neutrónica de boro (BNCT podría ser una alternativa para el tratamiento de esta enfermedad. Se basa en la captación selectiva de boro por el tumor y su activación por un haz de neutrones. El boro activado libera un núcleo de litio-7 y una partícula alfa, las cuales tienen una alta transmisión linear de energía (linear energy transfer, LET y un alcance de 5-9 µm, destruyendo el tumor. En estudios previos hemos mostrado que la línea celular humana de cáncer indiferenciado de tiroides (ARO tiene una captación selectiva de borofenilalanina (10BPA tanto in vitro como después de ser implantada en ratones NIH nude. También demostramos en estos animales inyectados con BPA e irradiados con un haz de neutrones térmicos, un 100% de control sobre el crecimiento tumoral y un 50% de cura histológica. En trabajos posteriores mostramos que la porfirina 10BOPP tetrakis-carborane carboxylate ester de 2,4-bis-(a,b-dihydroxyethyl-deutero-porphyrin IX cuando es inyectada 5-7 días antes que el BPA se obtiene una concentración tumoral de boro de aproximadamente el doble que el BPA solo (45-38 ppm vs. 20 ppm. La posterior irradiación con neutrones mostró un 100% de remisión completa en animales con tumores cuyo volumen pre-tratamiento era de 50 mm³ o menor. Los perros padecen CIT espontáneo, con un comportamiento biológico similar al humano, y una captación selectiva de BPA, abriendo la posibilidad de su tratamiento por BNCT.Undifferentiated thyroid carcinoma (UTC is an aggressive tumor with a poor prognosis due to the lack of an effective treatment. Boron neutron capture therapy (BNCT is based on the selective uptake of boron by the tumor and its activation by a neutron beam, releasing lithium-7 and an alpha particle that will kill the tumor cells by their high linear energy transfer (LET. In previous

  19. Biodistribution of Boron compounds in an experimental model of liver metastases for Boron Neutron Capture (BNCT) Studies

    International Nuclear Information System (INIS)

    Garabalino, Marcela A.; Monti Hughes, Andrea; Molinari, Ana J.; Heber, Elisa M.; Pozzi, Emiliano C.C.; Itoiz, Maria E.; Trivillin, Veronica A.; Schwint, Amanda E.; Nievas, Susana; Aromando, Romina F.

    2009-01-01

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10 B carriers in tumors followed by irradiation with thermal or epithermal neutrons. The high linear energy transfer alpha particles and recoiling 7 Li nuclei emitted during the capture of a thermal neutron by a 10 B nucleus have a short range and a high biological effectiveness. Thus, BNCT would potentially target neoplastic tissue selectively. In previous studies we demonstrated the therapeutic efficacy of different BNCT protocols in an experimental model of oral cancer. More recently we performed experimental studies in normal rat liver that evidenced the feasibility of treating liver metastases employing a novel BNCT protocol proposed by JEC based on ex-situ treatment and partial liver auto-transplant. The aim of the present study was to perform biodistribution studies with different boron compounds and different administration protocols to determine the protocols that would be therapeutically useful in 'in vivo' BNCT studies at the RA-3 Nuclear Reactor in an experimental model of liver metastases in rats. Materials and Methods. A total of 70 BDIX rats (Charles River Lab., MA, USA) were inoculated in the liver with syngeneic colon cancer cells DH/DK12/TRb (ECACC, UK) to induce the development of subcapsular metastatic nodules. 15 days post-inoculation the animals were used for biodistribution studies. A total of 11 protocols were evaluated employing the boron compounds boronophenylalanine (BPA) and GB-10 (Na 2 10 B 1 -0H 10 ), alone or combined employing different doses and administration routes. Tumor, normal tissue and blood samples were processed for boron measurement by ICP-OES. Results. Several protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue, i.e. BPA 15.5 mg 10 B/kg iv + GB-10 50 mg 10 B/kg iv; BPA 46.5 mg 10 B/kg ip; BPA 46.5 mg 10 B/kg ip

  20. Dosimetry methods in boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gambarini, G.; Artuso, E.; Felisi, M.; Regazzoni, V.; Giove, D. [Universita degli Studi di Milano, Department of Physics, Via Festa del Patrono 7, 20122 Milano (Italy); Agosteo, S.; Barcaglioni, L. [Istituto Nazionale di Fisica Nucleare, Milano (Italy); Campi, F.; Garlati, L. [Politecnico di Milano, Energy Department, Piazza Leonardo Da Vinci 32, 20133 Milano (Italy); De Errico, F. [Universita degli Studi di Pisa, Department of Civil and Industrial Engineering, Lungamo Pacinotti 43, 56126 Pisa (Italy); Borroni, M.; Carrara, M. [Fondazione IRCCS Istituto Nazionale Tumori, Medical Physics Unit, Via Venezian 1, 20133 Milano (Italy); Burian, J.; Klupak, V.; Viererbl, L.; Marek, M. [Research Centre Rez, Department of Neutron Physics, 250-68 Husinec-Rez (Czech Republic)

    2014-08-15

    Dosimetry studies have been carried out at thermal and epithermal columns of Lvr-15 research reactor for investigating the spatial distribution of gamma dose, fast neutron dose and thermal neutron fluence. Two different dosimetry methods, both based on solid state detectors, have been studied and applied and the accuracy and consistency of the results have been inspected. One method is based on Fricke gel dosimeters that are dilute water solutions and have good tissue equivalence for neutrons and also for all the secondary radiations produced by neutron interactions in tissue or water phantoms. Fricke gel dosimeters give the possibility of separating the various dose contributions, i.e. the gamma dose, the fast neutron dose and the dose due to charged particles generated during thermal neutron reactions by isotopes having high cross section, like 10-B. From this last dose, thermal neutron fluence can be obtained by means of the kerma factor. The second method is based on thermoluminescence dosimeters. In particular, the developed method draw advantage from the different heights of the peaks of the glow curve of such phosphors when irradiated with photons or with thermal neutrons. The results show that satisfactory results can be obtained with simple methods, in spite of the complexity of the subject. However, the more suitable dosimeters and principally their utilization and analysis modalities are different for the various neutron beams, mainly depending on the relative intensities of the three components of the neutron field, in particular are different for thermal and epithermal columns. (Author)

  1. Development of inverse-planning system for neutron capture therapy

    International Nuclear Information System (INIS)

    Kumada, Hiroaki; Yamamoto, Kazuyoshi; Maruo, Takeshi

    2006-01-01

    To lead proper irradiation condition effectively, Japan Atomic Energy Agency (JAEA) is developing an inverse-planning system for neutron capture therapy (NCT-IPS) based on the JAEA computational dosimetry system (JCDS) for BNCT. The leading methodology of an optimum condition in the NCT-IPS has been applied spatial channel theory with adjoint flux solution of Botzman transport. By analyzing the results obtained from the adjoint flux calculations according to the theory, optimum incident point of the beam against the patient can be found, and neutron spectrum of the beam which can generate ideal distribution of neutron flux around tumor region can be determined. The conceptual design of the NCT-IPS was investigated, and prototype of NCT-IPS with JCDS is being developed. (author)

  2. Physico-technical progress in neutron-capture therapy method

    International Nuclear Information System (INIS)

    Kanda, Keiji; Furubayashi, Toru; Aoki, Kazuhiko

    1985-01-01

    This paper describes mainly development studies on the determination method of in vivo 10 B for the purpose of employment for neutron capture therapy for malignant melanoma and other tumors. To darify the efficacy of the neutron capture therapy, it is necessary to determine 10 B concentration in the diseased part. This study aimed at in vivo 10 B concention determination in living sample to the level of ppm order with 10 % of analytical error within 1 hour, and these determination conditions were satified by prompt γ-ray (478 keV) determination of 10 B (n, αγ) 7 Li reaction. This method required no sample pretreatment. Further, data normalization by γ-ray of H(n, γ)D reaction permitted no disturbance by sample shape or size. Lower limit of detection of the proposed method was estimated in terms of measuring time and statistical error by the equations of 10 B concentration and error analysis derived by the authors. As for the effect of prompt γ-rays of 23 Na(n, γ) 24 Na and 6 Li(n, γ) 7 Li reactions, it was clarified that the former showed no disturbance but some correction was necessary in case of less than 0.1 g of smaple size owing to the latter reaction. In vivo sample determination showed the proposed method was practical. In this paper some results of phantom experiment for in vivo non-destructive 10 B measurement and related simulation calculation, and examination of effect of (γ, n) reaction in heavy water of biomedical irradiation equipment on radiation quality were also described. (Takagi, S.)

  3. Comparison of the image-derived radioactivity and blood-sample radioactivity for estimating the clinical indicators of the efficacy of boron neutron capture therapy (BNCT): 4-borono-2-18F-fluoro-phenylalanine (FBPA) PET study.

    Science.gov (United States)

    Isohashi, Kayako; Shimosegawa, Eku; Naka, Sadahiro; Kanai, Yasukazu; Horitsugi, Genki; Mochida, Ikuko; Matsunaga, Keiko; Watabe, Tadashi; Kato, Hiroki; Tatsumi, Mitsuaki; Hatazawa, Jun

    2016-12-01

    In boron neutron capture therapy (BNCT), positron emission tomography (PET) with 4-borono-2- 18 F-fluoro-phenylalanine (FBPA) is the only method to estimate an accumulation of 10 B to target tumor and surrounding normal tissue after administering 10 B carrier of L-paraboronophenylalanine and to search the indication of BNCT for individual patient. Absolute concentration of 10 B in tumor has been estimated by multiplying 10 B concentration in blood during BNCT by tumor to blood radioactivity (T/B) ratio derived from FBPA PET. However, the method to measure blood radioactivity either by blood sampling or image data has not been standardized. We compared image-derived blood radioactivity of FBPA with blood sampling data and studied appropriate timing and location for measuring image-derived blood counts. We obtained 7 repeated whole-body PET scans in five healthy subjects. Arterialized venous blood samples were obtained from the antecubital vein, heated in a heating blanket. Time-activity curves (TACs) of image-derived blood radioactivity were obtained using volumes of interest (VOIs) over ascending aorta, aortic arch, pulmonary artery, left and right ventricles, inferior vena cava, and abdominal aorta. Image-derived blood radioactivity was compared with those measured by blood sampling data in each location. Both the TACs of blood sampling radioactivity in each subject, and the TACs of image-derived blood radioactivity showed a peak within 5 min after the tracer injection, and promptly decreased soon thereafter. Linear relationship was found between blood sampling radioactivity and image-derived blood radioactivity in all the VOIs at any timing of data sampling (p radioactivity measured in the left and right ventricles 30 min after injection showed high correlation with blood radioactivity. Image-derived blood radioactivity was lower than blood sampling radioactivity data by 20 %. Reduction of blood radioactivity of FBPA in left ventricle after 30 min of FBPA

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

    Energy Technology Data Exchange (ETDEWEB)

    Trivillin, Veronica A.; Schwint, Amanda E. [Comision Nacional de Energia Atomica (CNEA), Department of Radiobiology, San Martin, Provincia Buenos Aires (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Bruno, Leandro J.; Gatti, David A. [Universidad Nacional de Rosario, LABOATEM (Laboratorio de Biologia Osteoarticular, Ingenieria Tisular y Terapias Emergentes), Facultad de Ciencias Medicas, Rosario (Argentina); Stur, Mariela [Universidad Nacional de Rosario, Catedra de Diagnostico por Imagenes, Facultad de Ciencias Medicas, Rosario (Argentina); Garabalino, Marcela A.; Hughes, Andrea Monti [Comision Nacional de Energia Atomica (CNEA), Department of Radiobiology, San Martin, Provincia Buenos Aires (Argentina); Castillo, Jorge; Wentzeis, Luis; Scolari, Hugo [Comision Nacional de Energia Atomica (CNEA), Department of Reactors, San Martin, Provincia Buenos Aires (Argentina); Pozzi, Emiliano C.C. [Comision Nacional de Energia Atomica (CNEA), Department of Research and Production Reactors, Ezeiza, Province Buenos Aires (Argentina); Feldman, Sara [Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Ciudad Autonoma de Buenos Aires (Argentina); Universidad Nacional de Rosario, LABOATEM (Laboratorio de Biologia Osteoarticular, Ingenieria Tisular y Terapias Emergentes), Facultad de Ciencias Medicas, Rosario (Argentina)

    2016-11-15

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  6. Musashi reactor adaption for both neutron capture therapy and neutron radiography

    International Nuclear Information System (INIS)

    Matsumoto, Tetsuo

    1999-01-01

    Neutron beam designs were studied at the proposed Musashi reactor (TRIGA-II, 100 kW) with a view to generating thermal and epithermal neutron beams for both neutron capture therapy (NCT) and neutron radiography (NR). The beams are delivered from thermal and thermalizing columns, and also horizontal beam hole. Thermal, epithermal and fast neutron energy ranges were selected as 10 keV, respectively. Several prospective neutron filters (aluminum (Al), aluminum oxide (Al 2 O 3 ), lead fluoride (PbF 2 ) and high-density graphite (G), bismuth (Bi), single-crystal silicon (Si)) were examined for obtaining sufficiently intense neutron beam. Monte Carlo calculations indicated that with a suitable neutron filter arrangement, thermal and epithermal neutron beams attaining 2x10 9 and 5x10 8 ncm -2 s -1 , respectively, could be obtainable from thermal and thermalizing columns with the reactor operating at 100 kW. These neutron beams could be adopted for boron neutron capture therapy. Compared with these columns, horizontal beam port would deliver neutron fluxes of from 10 -2 to 10 -3 lower intensity, but produced thermal and epithermal neutron beams would be adequate for different application to neutron radiography. (author)

  7. Hyper-thermal neutron irradiation field for neutron capture therapy

    International Nuclear Information System (INIS)

    Sakurai, Yoshinori; Kobayashi, Tooru; Kanda, Keiji

    1994-01-01

    The utilization of hyper-thermal neutrons, which have an energy spectrum of a Maxwell distribution higher than the room temperature of 300 K, has been studied in order to improve the thermal neutron flux distribution in a living body for a deep-seated tumor in neutron capture therapy (NCT). Simulation calculations using MCNP-V3 were carried out in order to investigate the characteristics of the hyper-thermal neutron irradiation field. From the results of simulation calculations, the following were confirmed: (i) The irradiation field of the hyper-thermal neutrons is feasible by using some scattering materials with high temperature, such as Be, BeO, C, SiC and ZrH 1.7 . Especially, ZrH 1.7 is thought to be the best material because of good characteristics of up-scattering for thermal neutrons. (ii) The ZrH 1.7 of 1200 K yields the hyper-thermal neutrons of a Maxwell-like distribution at about 2000 K and the treatable depth is about 1.5 cm larger comparing with the irradiation of the thermal neutrons of 300 K. (iii) The contamination by the secondary gamma-rays from the scattering materials can be sufficiently eliminated to the tolerance level for NCT through the bismuth layer, without the larger change of the energy spectrum of hyper-thermal neutrons. ((orig.))

  8. Gadolinium neutron capture therapy for brain tumors. Biological aspects

    International Nuclear Information System (INIS)

    Takagaki, Masao; Oda, Yoshifumi; Matsumoto, Masato; Kikuchi, Haruhiko; Kobayashi, Tooru; Kanda, Keiji; Ujeno, Yowri.

    1994-01-01

    This study investigated the tumoricidal effect of gadolinium neutron capture therapy (Gd-NCT) in in vitro and in vivo systems using Gd-DTPA. In in vitro study, a certain amount of Gd-DTPA, yielding 5000 ppm Gd-n, was added to human glioma cells, T98G, upon which thermal neutrons were exposed. After irradiation, the cells were incubated and the colonies were counted 10 days later. In in vivo study, Fisher-344 rats with experimentally induced gliosarcoma cells (9L) were exposed to thermal neutrons at a fluence rate of 3E+9/s for 1 h immediately after iv injection of Gd-DTPA. Two weeks after irradiation, brain samples were histologically examined. Tumor clearance of Gd-DTPA was also determined. In vitro analysis showed that a 1% survival level was obtained at 3.75E+12 (n/cm 2 ) for the Gd (+) medium and 2.50E+13 (n/cm 2 ) for the Gd (-) medium. In in vivo analysis, the concentration of Gd in 9L-rat brain tumor after iv injection of 0.2 mg/kg Gd-DTPA was found to be less than 100 ppm, but Gd-NCT on 9L-rat brain tumor administered with a ten-fold dose showed a substantial killing effect on tumor without serious injury to the normal brain structure. The killing effect of Gd-NCT was confirmed in in vitro and in vivo systems. (N.K.)

  9. {sup 10}B uptake by cells for boron neutron capture synovectomy

    Energy Technology Data Exchange (ETDEWEB)

    Binello, E.; Yanch, J.C. [MIT, Department of Nuclear Engineering, Cambridge, MA (United States); Shortkroff, S. [Brigham and Women' s Hospital, Department of Orthopedic Surgery, Boston, MA (United States)

    2000-10-01

    Boron Neutron Capture Synovectomy (BNCS) proposes to use the {sup 10}B(n,{alpha}){sup 7}Li reaction to ablate inflamed synovium (a tissue lining articular joints) in patients with Rheumatoid Arthritis. Boron uptake is an important parameter for treatment design. In this study, a simple method was developed to determine K{sub 2}B{sub 12}H{sub 12} (KBH) uptake in vitro by non-adhering monocytic cells (representative of synovial cells in inflamed joints). Uptake was quantified as a function of incubation time and boron concentration, as well as following washout: no significant difference was found between incubation times tested; average uptake ranged from 55 to 60% of {sup 10}B incubation concentrations varying from 1000 to 5000 ppm: approximately 15% of the {sup 10}B concentration was measured upon re-incubation in boron-free medium. These results agree well with those obtained ex vivo using human arthritic synovium, a significant finding in light of the difficulty typically associated with obtaining such tissue. The full characterization of {sup 10}B uptake for BNCS (with KBH) is discussed. (author)

  10. Monte-Carlo simulation of primary stochastic effects induced at the cellular level in boron neutron capture therapy; Simulation Monte-Carlo des effets stochastiques primaires induits au niveau cellulaire lors de la therapie par capture de neutrons sur le {sup 10}B

    Energy Technology Data Exchange (ETDEWEB)

    Cirioni, L.; Patau, J.P.; Nepveu, F. [Universite Paul Sabatier, 31 - Toulouse (France)

    1998-04-01

    A Monte Carlo code is developed to study the action of particles in Boron Neutron Capture Therapy (BNCT). Our aim is to calculate the probability of dissipating a lethal dose in cell nuclei. Cytoplasmic and nuclear membranes are considered as non-concentric ellipsoids. All geometrical parameters may be adjusted to fit actual configurations. The reactions {sup 10}B(n,{gamma} {alpha}){sup 7}Li and {sup 14}N(n,p) {sup 14}C create heavy ions which slow clown losing their energy. Their trajectories can be simulated taking into account path length straggling. The contribution of each reaction to the deposited dose in different cellular compartments can be studied and analysed for any distribution of {sup 10}B. (authors)

  11. Establishment of optimal thermal neutron capture therapy for 5 types of human malignant melanoma

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1993-03-01

    A series of boron neutron capture therapy (BNCT) studies has already germinated in 1972, with a view to establishing the BNCT particularly suited for the treatment of various types of malignant melanoma, and has been succeeded by research teams comprised of multi-disciplinary members. Twelve patients (7 men and 5 women, aged from 50 to 85 years) with malignant melanoma have been treated with BNCT; among them, six patients were completely cured, four had extremely reduced tumors, and two were still in the clinical process. The present Progress Report is a compilation of 39 research presentations for the recent two years. In this report, three patients are described. Of these, one patient had deep-seated lesions in right and left lymph nodes. These lesions were cured by the use of D 2 O that allowed neutron beams to reach them. Application of positron emission tomography to the diagnosis of melanoma is a highlight in this Report. (N.K.)

  12. Synovectomy by neutron capture in boron; Sinovectomia por captura de neutrones en boro

    Energy Technology Data Exchange (ETDEWEB)

    Vega C, H.R. [Unidades Academicas de Estudios Nucleares, Ingenieria Electrica y Matematicas, Universidad Autonoma de Zacatecas, A.P. 336, C.P. 98000 Zacatecas (Mexico)

    2002-07-01

    The rheumatoid arthritis is an illness which affect approximately at 3% of the World population. This illness is characterized by the inflammation of the joints which reduces the quality of life and the productivity of the patients. Since, it is an autoimmune illness, the inflammation is due to the overproduction of synovial liquid by the increase in the quantity of synoviocytes. The rheumatoid arthritis does not have a definitive recovery and the patients have three options of treatment: the use of drugs, the surgery and the radio synovectomy. The synovectomy by neutron capture in Boron is a novel proposal of treatment of the rheumatoid arthritis that consists in using a charged compound with Boron 10 that is preferently incorporated in the synoviocytes and to a less extent in the rest of surrounding tissues of the joint. Then, the joint is exposed to a thermal neutron field that induces the reaction (n, {alpha}) in the {sup 10} B. the products of this reaction place their energy inside synoviocytes producing their reduction and therefore the reduction of the joint inflammation. Since it is a novel procedure, the synovectomy by neutron capture in boron has two problems: the source design and the design of the adequate drug. In this work it has been realized a Monte Carlo study with the purpose to design a moderating medium that with a {sup 239} Pu Be source in its center, produces a thermal neutron field. With the produced neutron spectra, the neutrons spectra and neutron doses were calculated in different sites inside a model of knee joint. In Monte Carlo studies it is necessary to know the elemental composition of all the joint components, for the case of synovia and the synovial liquid this information does not exist in such way that it is supposed that its composition is equal than the water. In this work also it has been calculated the kerma factors by neutrons of synovia and the synovial liquid supposing that their elemental composition are similar to the

  13. Boron neutron capture irradiation of the rat spinal cord: effects of variable doses of borocaptate sodium

    International Nuclear Information System (INIS)

    Morris, Gerard M.; Coderre, Jeffrey A.; Hopewell, John W.; Micca, Peggy L.; Fisher, Craig

    1996-01-01

    The Fischer 344 rat spinal cord model has been used to evaluate the response of the central nervous system to boron neutron capture irradiation with variable doses of the neutron capture agent, borocaptate sodium (BSH). Three doses of BSH, 190, 140 and 80 mg/kg body weight, administered by i.p. injection, were used to establish the time course of 10 B accumulation in and removal from the blood. After administration of the two lower doses of BSH, blood 10 B levels peaked at 0.5 h after injection, with no significant (P > 0.1) change at 1 h after injection. Beyond this time point, levels of 10 B in the blood began to decrease after a dose of 80 mg/kg BSH, but remained constant until 3 h after administration after the two higher doses of BSH. Myelopathy developed after latent intervals of 20.4 ± 0.1, 20.8 ± 1.4, 15.0 ± 0.8, 15.4 ± 0.4 and 15.6 ± 0.4 weeks, following irradiation with thermal neutrons in combination with BSH at doses of 20, 40, 80, 140 and 190 mg/kg body weight, respectively. The radiation-induced lesion in the spinal cord was white matter necrosis. ED 50 values for myelopathy were calculated from probit-fitted dose-effect curves. Expressed as total physical absorbed doses, these values were 20.7 ± 1.9, 24.9 ± 1.2, 27.2 ± 0.9, 28.4 ± 0.6 and 32.4 ± 1.9 Gy after irradiation with thermal neutrons in the presence of 20, 40, 80, 140 and 190 mg/kg body weight of BSH, respectively. The compound biological effectiveness (CBE) factor values, estimated from this data, were in the range 0.49-0.55. There was no significant (P >0.1) variation in the CBE factor for BSH as a function of increasing 10 B concentration in the blood. It was concluded that there was no significant synergistic interaction between the low and high linear energy transfer (LET) components of the boron neutron capture (BNC) radiation field

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

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jay [Department of Radiological Technology, Central Taiwan University of Science and Technology, Taiwan (China); Chang, S-J [Health Physics Division, Institute of Nuclear Energy Research, Atomic Energy Council, Taiwan (China); Chuang, K-S [Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Taiwan (China); Hsueh, Y-W [Department of Engineering and System Science, National Tsing-Hua University, Taiwan (China); Yeh, K-C [Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Taiwan (China); Wang, J-N [Department of Engineering and System Science, National Tsing-Hua University, Taiwan (China); Tsai, W-P [Division of Rheumatology, Immunology and Allergy, Chang Gung Memorial Hospital, Taiwan (China)

    2007-03-21

    Rheumatoid arthritis is one of the most common epidemic diseases in the world. For some patients, the treatment with steroids or nonsteroidal anti-inflammatory drugs is not effective, thus necessitating physical removal of the inflamed synovium. Alternative approaches other than surgery will provide appropriate disease control and improve the patient's quality of life. In this research, we evaluated the feasibility of conducting boron neutron capture synovectomy (BNCS) with the Tsing Hua open-pool reactor (THOR) as a neutron source. Monte Carlo simulations were performed with arthritic joint models and uncertainties were within 5%. The collimator, reflector and boron concentration were optimized to reduce the treatment time and normal tissue doses. For the knee joint, polyethylene with 40%-enriched Li{sub 2}CO{sub 3} was used as the collimator material, and a rear reflector of 15 cm thick graphite and side reflector of 10 cm thick graphite were chosen. The optimized treatment time was 5.4 min for the parallel-opposed irradiation. For the finger joint, polymethyl methacrylate was used as the reflector material. The treatment time can be reduced to 3.1 min, while skin and bone doses can be effectively reduced by approximately 9% compared with treatment using the graphite reflector. We conclude that using THOR as a treatment modality for BNCS could be a feasible alternative in clinical practice.

  15. From boron analogues of amino acids to boronated DNA: potential new pharmaceuticals and neutron capture agents

    International Nuclear Information System (INIS)

    Spielvogel, B.F.; Sood, Anup; Duke Univ., Durham, NC; Shaw, B.R.; Hall, I.H.

    1991-01-01

    Isoelectronic and isostructural boron analogues of the α-amino acids ranging from simple glycine analogues such as H 3 NBH 2 COOH and Me 2 NHBH 2 COOH to alanine analogues have been synthesised. A diverse variety of analogues, including precursors and derivatives (such as peptides) have potent pharmacological activity, including anticancer, antiinflammatory, analgesic, and hypolipidemic activity in animal model studies and in vitro cell cultures. Boronated nucleosides and (oligo)nucleotides, synthetic oligonucleotide analogues of ''antisense'' agents interact with a complementary nucleic acid sequence blocking the biological effect of the target sequence. Nucleosides boronated on the pyrimidine and purine bases have been prepared. It has been established that an entirely new class of nucleic acid derivatives is feasible in which one of the non-bridging oxygens in the internucleotide phosphodiester linkage can be replaced by an isoelectronic analogue, the borane group, (BH 3 ). The boronated oligonucleotides can be viewed as hybrids of the normal oxygen oligonucleotides and the methylphosphonate oligonucleotides. (author)

  16. Further development of thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1995-03-01

    This issue is the collection of the papers presented thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma. Separate abstracts were prepared for 2 of the papers in this report. The remaining 32 papers were considered outside the subject scope of INIS. (J.P.N.)

  17. High power accelerator-based boron neutron capture with a liquid lithium target and new applications to treatment of infectious diseases

    Energy Technology Data Exchange (ETDEWEB)

    Halfon, S. [Soreq NRC, Yavne 81800 (Israel); Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel)], E-mail: halfon@phys.huji.ac.il; Paul, M. [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel); Steinberg, D. [Biofilm Laboratory, Institute of Dental Sciences, Faculty of Dentistry, Hebrew University-Hadassah (Israel); Nagler, A.; Arenshtam, A.; Kijel, D. [Soreq NRC, Yavne 81800 (Israel); Polacheck, I. [Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center (Israel); Srebnik, M. [Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Hebrew University, Jerusalem 91120 (Israel)

    2009-07-15

    A new conceptual design for an accelerator-based boron neutron capture therapy (ABNCT) facility based on the high-current low-energy proton beam driven by the linear accelerator at SARAF (Soreq Applied Research Accelerator Facility) incident on a windowless forced-flow liquid-lithium target, is described. The liquid-lithium target, currently in construction at Soreq NRC, will produce a neutron field suitable for the BNCT treatment of deep-seated tumor tissues, through the reaction {sup 7}Li(p,n){sup 7}Be. The liquid-lithium target is designed to overcome the major problem of solid lithium targets, namely to sustain and dissipate the power deposited by the high-intensity proton beam. Together with diseases conventionally targeted by BNCT, we propose to study the application of our setup to a novel approach in treatment of diseases associated with bacterial infections and biofilms, e.g. inflammations on implants and prosthetic devices, cystic fibrosis, infectious kidney stones. Feasibility experiments evaluating the boron neutron capture effectiveness on bacteria annihilation are taking place at the Soreq nuclear reactor.

  18. High power accelerator-based boron neutron capture with a liquid lithium target and new applications to treatment of infectious diseases

    International Nuclear Information System (INIS)

    Halfon, S.; Paul, M.; Steinberg, D.; Nagler, A.; Arenshtam, A.; Kijel, D.; Polacheck, I.; Srebnik, M.

    2009-01-01

    A new conceptual design for an accelerator-based boron neutron capture therapy (ABNCT) facility based on the high-current low-energy proton beam driven by the linear accelerator at SARAF (Soreq Applied Research Accelerator Facility) incident on a windowless forced-flow liquid-lithium target, is described. The liquid-lithium target, currently in construction at Soreq NRC, will produce a neutron field suitable for the BNCT treatment of deep-seated tumor tissues, through the reaction 7 Li(p,n) 7 Be. The liquid-lithium target is designed to overcome the major problem of solid lithium targets, namely to sustain and dissipate the power deposited by the high-intensity proton beam. Together with diseases conventionally targeted by BNCT, we propose to study the application of our setup to a novel approach in treatment of diseases associated with bacterial infections and biofilms, e.g. inflammations on implants and prosthetic devices, cystic fibrosis, infectious kidney stones. Feasibility experiments evaluating the boron neutron capture effectiveness on bacteria annihilation are taking place at the Soreq nuclear reactor.

  19. Hormone receptor densities in relation to 10B neutron capture therapy

    International Nuclear Information System (INIS)

    Hechter, O.; Schwartz, I.L.

    1982-01-01

    This presentation is a theoretical discussion of the possibility that appropriate steroid-carborane derivatives might be used to selectively deliver boron-10 ( 10 B) to tumor cells with sex-hormone receptors in sufficient concentration for effective neutron capture theory (NCT) of hormone-dependent mammary and prostatic cancer. The results indicate the concentrations of androgen receptors (AR) and progesterone receptors (PR) in malignant prostatic cells or of estrogen receptors (ER) in malignant mammary cells are two low to achieve nuclear 10 B concentrations of 1 + g per g of tumor by using a steroid ligand coupled to a single carborane cage

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

    International Nuclear Information System (INIS)

    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 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Application of neutron capture autoradiography to Boron Delivery seeking techniques for selective accumulation of boron compounds to tumor with intra-arterial administration of boron entrapped water-in-oil-in-water emulsion

    Science.gov (United States)

    Mikado, S.; Yanagie, H.; Yasuda, N.; Higashi, S.; Ikushima, I.; Mizumachi, R.; Murata, Y.; Morishita, Y.; Nishimura, R.; Shinohara, A.; Ogura, K.; Sugiyama, H.; Iikura, H.; Ando, H.; Ishimoto, M.; Takamoto, S.; Eriguchi, M.; Takahashi, H.; Kimura, M.

    2009-06-01

    It is necessary to accumulate the 10B atoms selectively to the tumor cells for effective Boron Neutron Capture Therapy (BNCT). In order to achieve an accurate measurement of 10B accumulations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of sliced samples of tumor tissues using CR-39 plastic track detectors. The CR-39 track detectors attached with the biological samples were exposed to thermal neutrons in the thermal column of the JRR3 of Japan Atomic Energy Agency (JAEA). We obtained quantitative NCAR images of the samples for VX-2 tumor in rabbit liver after injection of 10BSH entrapped water-in-oil-in-water (WOW) emulsion by intra-arterial injection via proper hepatic artery. The 10B accumulations and distributions in VX-2 tumor and normal liver of rabbit were investigated by means of alpha-track density measurements. In this study, we showed the selective accumulation of 10B atoms in the VX-2 tumor by intra-arterial injection of 10B entrapped WOW emulsion until 3 days after injection by using digitized NCAR images (i.e. alpha-track mapping).

  3. Application of neutron capture autoradiography to Boron Delivery seeking techniques for selective accumulation of boron compounds to tumor with intra-arterial administration of boron entrapped water-in-oil-in-water emulsion

    International Nuclear Information System (INIS)

    Mikado, S.; Yanagie, H.; Yasuda, N.; Higashi, S.; Ikushima, I.; Mizumachi, R.; Murata, Y.; Morishita, Y.; Nishimura, R.; Shinohara, A.; Ogura, K.; Sugiyama, H.; Iikura, H.; Ando, H.; Ishimoto, M.; Takamoto, S.; Eriguchi, M.; Takahashi, H.; Kimura, M.

    2009-01-01

    It is necessary to accumulate the 10 B atoms selectively to the tumor cells for effective Boron Neutron Capture Therapy (BNCT). In order to achieve an accurate measurement of 10 B accumulations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of sliced samples of tumor tissues using CR-39 plastic track detectors. The CR-39 track detectors attached with the biological samples were exposed to thermal neutrons in the thermal column of the JRR3 of Japan Atomic Energy Agency (JAEA). We obtained quantitative NCAR images of the samples for VX-2 tumor in rabbit liver after injection of 10 BSH entrapped water-in-oil-in-water (WOW) emulsion by intra-arterial injection via proper hepatic artery. The 10 B accumulations and distributions in VX-2 tumor and normal liver of rabbit were investigated by means of alpha-track density measurements. In this study, we showed the selective accumulation of 10 B atoms in the VX-2 tumor by intra-arterial injection of 10 B entrapped WOW emulsion until 3 days after injection by using digitized NCAR images (i.e. alpha-track mapping).

  4. Application of neutron capture autoradiography to Boron Delivery seeking techniques for selective accumulation of boron compounds to tumor with intra-arterial administration of boron entrapped water-in-oil-in-water emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Mikado, S. [Physical Science Laboratories, College of Industrial Technology, Nihon University, Chiba (Japan)], E-mail: mikado@cit.nihon-u.ac.jp; Yanagie, H. [Department of Nuclear Engineering and Management, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Yasuda, N. [Fundamental Technology Center, National Institute of Radiological Sciences, Chiba (Japan); Higashi, S.; Ikushima, I. [Miyakonojyo Metropolitan Hospital, Miyazaki (Japan); Mizumachi, R.; Murata, Y. [Department of Pharmacology, Kumamoto Institute Branch, Mitsubishi Chemical Safety Institute Ltd., Kumamoto (Japan); Morishita, Y. [Department of Human and Molecular Pathology, University of Tokyo, Tokyo (Japan); Nishimura, R. [Faculty of Agriculture, Laboratory of Veterinary Surgery, University of Tokyo (Japan); Shinohara, A. [Department of Humanities, The Graduate School of Seisen University, Tokyo (Japan); Ogura, K. [Physical Science Laboratories, College of Industrial Technology, Nihon University, Chiba (Japan); Sugiyama, H. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Iikura, H.; Ando, H. [Japan Atomic Energy Agency, Ibaraki (Japan); Ishimoto, M. [Department of Nuclear Professional School, University of Tokyo (Japan); Takamoto, S. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Cardiac Surgery, University of Tokyo Hospital, Tokyo (Japan); Eriguchi, M. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Microbiology, Syowa University School of Pharmaceutical Sciences, Tokyo (Japan); Takahashi, H. [Department of Nuclear Engineering and Management, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Kimura, M. [Department of Physics, Toho University, Chiba (Japan)

    2009-06-21

    It is necessary to accumulate the {sup 10}B atoms selectively to the tumor cells for effective Boron Neutron Capture Therapy (BNCT). In order to achieve an accurate measurement of {sup 10}B accumulations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of sliced samples of tumor tissues using CR-39 plastic track detectors. The CR-39 track detectors attached with the biological samples were exposed to thermal neutrons in the thermal column of the JRR3 of Japan Atomic Energy Agency (JAEA). We obtained quantitative NCAR images of the samples for VX-2 tumor in rabbit liver after injection of {sup 10}BSH entrapped water-in-oil-in-water (WOW) emulsion by intra-arterial injection via proper hepatic artery. The {sup 10}B accumulations and distributions in VX-2 tumor and normal liver of rabbit were investigated by means of alpha-track density measurements. In this study, we showed the selective accumulation of {sup 10}B atoms in the VX-2 tumor by intra-arterial injection of {sup 10}B entrapped WOW emulsion until 3 days after injection by using digitized NCAR images (i.e. alpha-track mapping)

  5. Boron neutron capture therapy: An interdisciplinary co-operation

    International Nuclear Information System (INIS)

    Sauerwein, W.; Hideghety, K.; Rassow, J.; Moss, R.L.; Stecher-Rasmussen, F.; Heimans, J.; Gabel, D.; Vries, M.J. de; Touw, D.J.

    2001-01-01

    The international (European) undertaking in BNCT in the Netherlands has required close scrutiny of the organisational structure required to establish BNCT facilities. The multidisciplinary co-operation and the tasks of the participants in the hospital (Radiation Oncologist, Medical Physicist, Pharmacist and other medical and paramedical staff) and those attached to the reactor) are described. The organisational structure and regulatory aspects required for the international functioning of the Petten treatment facility are provided for guidance to new projects in this field. (author)

  6. Final Report: 8th International Symposium on Neutron Capture Therapy (NCT) for Cancer, May 15, 1998 - May 15, 1999

    International Nuclear Information System (INIS)

    Hawthorne, M.F.

    1999-01-01

    The 8th International Symposium on Neutron Capture Therapy for Cancer (8th ISNCTC) was held in La Jolla, CA on Sept. 13-18, 1998. This biennial meeting of the International Society for Neutron Capture Therapy (ISNCT) was hosted by Society President M.F. Hawthorne (UCLA Dept. of Chemistry and Biochemistry). The Symposium brought together scientists (300 registrants from 21 countries) from diverse fields to report the latest developments in NCT. Topics of the 275 papers presented (30 plenary lectures, 81 oral presentations, and 164 posters) included the physics of neutron sources, chemistry of tumor-targeting agents, dosimetry, radiobiological studies, and clinical applications

  7. BINP pilot accelerator-based neutron source for neutron capture therapy

    International Nuclear Information System (INIS)

    Belchenko, Yuriy; Burdakov, Alexander; Davydenko, Vladimir; Ivanov, Alexander; Kobets, Valeriy; Kudryavtsev, Andrey; Savkin, Valeriy; Shirokov, Valeriy; Taskaev, Sergey

    2006-01-01

    Neutron source based on accelerator has been proposed for neutron capture therapy at hospital. Innovative approach is based upon tandem accelerator with vacuum insulation and near threshold 7 Li(p,n) 7 Be neutron generation. Pilot innovative accelerator based neutron source is under going to start operating now at BINP, Novosibirsk. Negative ion source with Penning geometry of electrodes has been manufactured and dc H - ion beam has been obtained. Study of beam transport was carried out using prototype of tandem accelerator. Tandem accelerator and ion optical channels have been manufactured and assembled. Neutron producing target has been manufactured, thermal regimes of target were studied, and lithium evaporation on target substrate was realized. In the report, the pilot facility design is given and design features of facility components are discussed. Current status of project realization, results of experiments and simulations are presented. (author)

  8. Dosimetric characteristics of the thermal neutron beam facility for neutron capture therapy at Hanaro reactor

    International Nuclear Information System (INIS)

    Lee, Dong Han; Suh, Soheigh; Ji, Young Hoon

    2006-01-01

    The thermal neutron beam facility utilizing a typical tangential beam port for Neutron Capture Therapy was installed at the Hanaro, 30 MW multi-purpose research reactor. In order to determine the different dose components in phantoms irradiated with a mixed thermal neutron beam and gamma-ray for clinical applications, various techniques were applied including the use of activation foils, TLDs and ionization chambers. The water phantom was utilized in the measurement. The results of the measurement were compared with MCNP4B calculations. The thermal neutron fluxes were 1.02E9 and 6.07E8/cm 2 ·s at 10 and 20 mm depth in water, respectively. The gamma-ray dose rate was 5.10 Gy/hr at 20 mm depth in water. The result of this study can be used as basic data for subsequent BNCT clinical application. (author)

  9. Phantom experiment of depth-dose distributions for gadolinium neutron capture therapy

    International Nuclear Information System (INIS)

    Matsumoto, T.; Kato, K.; Sakuma, Y.; Tsuruno, A.; Matsubayashi, M.

    1993-01-01

    Depth-dose distributions in a tumor simulated phantom were measured for thermal neutron flux, capture gamma-ray and internal conversion electron dose rates for gadolinium neutron capture therapy. The results show that (i) a significant dose enhancement can be achieved in the tumor by capture gamma-rays and internal conversion electrons but the dose is mainly due to capture gamma-rays from the Gd(n, γ) reactions, therefore, is not selective at the cellular level, (ii) the dose distribution was a function of strongly interrelated parameters such as gadolinium concentrations, tumor site and neutron beam size (collimator aperture size), and (iii) the Gd-NCT by thermal neutrons appears to be a potential for treatment of superficial tumor. (author)

  10. Synovectomy by Neutron capture

    International Nuclear Information System (INIS)

    Vega C, H.R.; Torres M, C.

    1998-01-01

    The Synovectomy by Neutron capture has as purpose the treatment of the rheumatoid arthritis, illness which at present does not have a definitive curing. This therapy requires a neutron source for irradiating the articulation affected. The energy spectra and the intensity of these neutrons are fundamental since these neutrons induce nuclear reactions of capture with Boron-10 inside the articulation and the freely energy of these reactions is transferred at the productive tissue of synovial liquid, annihilating it. In this work it is presented the neutron spectra results obtained with moderator packings of spherical geometry which contains in its center a Pu 239 Be source. The calculations were realized through Monte Carlo method. The moderators assayed were light water, heavy water base and the both combination of them. The spectra obtained, the average energy, the neutron total number by neutron emitted by source, the thermal neutron percentage and the dose equivalent allow us to suggest that the moderator packing more adequate is what has a light water thickness 0.5 cm (radius 2 cm) and 24.5 cm heavy water (radius 26.5 cm). (Author)

  11. A physical and engineering study on the irradiation techniques in neutron capture therapy aiming for wider application

    International Nuclear Information System (INIS)

    Sakurai, Y.; Ono, K.; Suzuki, M.; Katoh, I.; Miyatake, S.-I.; Yanagie, H.

    2003-01-01

    The solo-irradiation of thermal neutrons has been applied for brain cancer and malignant melanoma in the boron neutron capture therapy (BNCT) at the medical irradiation facility of Kyoto University Reactor (KUR), from the first clinical trial in 1974. In 1997, after the facility remodeling, the application of the mix-irradiation of thermal and epi-thermal neutrons was started, and the depth dose distribution for brain cancer has been improved in some degree. In 2001, the solo-irradiation of epi-thermal neutrons also started. It is specially mentioned that the application to oral cancers started at the same time. The BNCT clinical trial using epi-thermal neutron irradiation at KUR, amounts to twelve as of March 2003. The seven trials; more than a half of the total trials, are for oral cancers. From this fact, we think that the wider application to the other cancers is required for the future prosperity of BNCT. The cancers applied for BNCT in KUR at the present time, are brain cancer, melanoma and oral cancers, as mentioned above. The cancers, expected to be applied in near future, are liver cancer, pancreas cancer, lung cancer, tongue cancer, breast cancer, etc.. Any cancer is almost incurable by the other therapy including the other radiation therapy. In the wider application of BNCT to these cancers, the dose-distribution control suitable to each cancer and/or each part, is important. The introduction of multi-directional and/or multi-divisional irradiation is also needed. Here, a physical and engineering study using two-dimensional transport calculation and three-dimensional Monte-Carlo simulation for the irradiation techniques in BNCT aiming for wider application is reported

  12. Improvement of JCDS, a computational dosimetry system in JAEA for neutron capture therapy

    International Nuclear Information System (INIS)

    Kumada, Hiroaki; Yamamoto, Kazuyoshi; Matsumura, Akira; Yamamoto, Tetsuya; Nakagawa, Yoshinobu; Kageji, Teruyoshi

    2006-01-01

    JCDS, a computational dosimetry system for neutron capture therapy, was developed by Japan Atomic Energy Agency. The system has been sophisticated to facilitate dose planning so far. In dosimetry with JCDS for BNCT clinical trials at JRR-4, several absorbed doses and the dose distributions are determined by a voxel model consisted of 2x2x2mm 3 voxel cells. By using the detailed voxel model, accuracy of the dosimetry can be improved. Clinical trials for melanoma and head-and-neck cancer as well as brain tumor were started using hot version of JCDS in 2005. JCDS is also being of improved so as to enable a JCDS application to dosimetry by PHITS as well as dosimetry by MCNP. By using PHITS, total doses of a patient by a combined modality therapy, for example a combination of BNCT and proton therapy, can be estimated consistently. Moreover, PET images can be adopted in combination with CT and MRI images as a farsighted approach. JCDS became able to identify target regions by using the PET values. (author)

  13. Contemporary state of neutron capture therapy in the Czech Republic - (Part 2)

    Czech Academy of Sciences Publication Activity Database

    Dbalý, V.; Tovaryš, F.; Honová, H.; Petruželka, L.; Prokeš, K.; Burian, J.; Marek, M.; Honzátko, Jaroslav; Tomandl, Ivo; Kříž, O.; Janků, I.; Mareš, Vladislav

    2003-01-01

    Roč. 66, č. 1 (2003), s. 60-63 ISSN 1210-7859 Institutional research plan: CEZ:AV0Z5011922; CEZ:AV0Z1048901 Keywords : boron neutron therapy * radiotherapy Subject RIV: FH - Neurology Impact factor: 0.047, year: 2003

  14. A study on the utilization of hyper-thermal neutrons for neutron capture therapy

    International Nuclear Information System (INIS)

    Sakurai, Yoshinori; Kobayashi, Tooru; Kanda, Keiji

    1993-01-01

    The utilization of hyper-thermal neutrons, which have an energy spectrum of a Maxwellian distribution of a higher temperature than the room temperature of 300 K, was studied in order to improve the thermal neutron flux distribution at the deeper part in a living body for neutron capture therapy. Simulation calculations were carried out using MCNP-V3 in order to confirm the characteristics of hyper-thermal neutrons, i.e., (1) depth dependence of neutron energy spectrum, and (2) depth distribution of the reaction rate in a water phantom for materials with 1/v neutron absorption. It is confirmed that the hyper-thermal neutron irradiation can improve the thermal neutron flux distribution in the deeper and wider area in a living body compared with the thermal neutron irradiation. Practically, by the incidence of the hyper-thermal neutrons with a 3000 K Maxwellian distribution, the thermal neutron flux at 5 cm depth can be given about four times larger than by the incidence of the thermal neutrons of 300 K. (author)

  15. Comparison of doses delivered in clinical trials of neutron capture therapy in the USA

    International Nuclear Information System (INIS)

    Albritton, J.R.; Binns, P.J.; Riley, K.J.; Coderre, J.A.; Harling, O.K.; Kiger, W.S. III

    2006-01-01

    A combined 81 brain tumor patients have been treated in dose escalation trials of Neutron Capture Therapy (NCT) at Harvard-MIT and Brookhaven National Laboratory (BNL). Pooling the clinical outcomes from these trials will permit evaluation with more statistical rigor. However, differences in physical and computational dosimetry between the institutions make direct comparison of the clinical dosimetry difficult. This paper describes work performed to normalize the BNL clinical dosimetry to that of Harvard-MIT for combined dose response analysis. This normalization involved analysis of MIT measurements and calculations using the BNL treatment planning system (TPS), BNCT - Rtpe, for two different phantoms. The BNL TPS was calibrated to dose measurements made by MIT at the BMRR in the BNL calibration phantom, a Lucite cube, and then validated by MIT dose measurements at the BMMR in an ellipsoidal water phantom. Treatment plans for all BNL patients were recomputed using the newly determined TPS calibration, yielding reductions in reported mean brain doses of 19% on average in the initial 15 patients and 31% in the latter 38 patients. These reductions in reported doses have clinically significant implications for those relying on reported BNL doses as a basis for initial dose selection in clinical studies. (author)

  16. Development of reference problems for neutron capture therapy treatment planning systems

    International Nuclear Information System (INIS)

    Albritton, J.R.; Kiger, W.S. III

    2006-01-01

    Currently, 5 different treatment planning systems (TPSs) are or have been used in clinical trials of Neutron Capture Therapy (NCT): MacNCTPlan, NCTPlan, BNCT Rtpe, SERA, and JCDS. This paper describes work performed to comprehensively test and compare 4 of these NCT treatment planning systems in order to facilitate the pooling of patient data from the different clinical sites for analysis of the clinical results as well as to provide an important quality assurance tool for existing and future TPSs. Two different phantoms were used to evaluate the planning systems: the modified Snyder head phantom and a large water-filled box, similar to that used in the International Dosimetry Exchange for NCT. The comparison of the resulting dose profile, isodose contours, and dose volume histograms to reference calculations performed with the Monte Carlo radiation transport code MCNP5 yielded many interesting differences. Each of the planning systems deviated from the reference calculations, with the newer systems (i.e., SERA and NCTPlan) most often yielding better agreement than their predecessors (i.e., BNCT Rtpe and MacNCTPlan). The combination of simple phantoms and sources with more complicated and realistic planning conditions has produced a well-rounded and useful suite of test problems for NCT treatment planning system analysis. (author)

  17. Boron Neutron Capture Therapty (BNCT) in an Oral Precancer Model: Therapeutic Benefits and Potential Toxicity of a Double Application of BNCT with a Six-Week Interval

    Energy Technology Data Exchange (ETDEWEB)

    Andrea Monti Hughes; Emiliano C.C. Pozzi; Elisa M. Heber; Silvia Thorp; Marcelo Miller; Maria E. Itoiz; Romina F. Aromando; Ana J. Molinari; Marcela A. Garabalino; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2011-11-01

    Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10 + BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB- 10 + BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10 + BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.

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

    Science.gov (United States)

    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

  19. Boron neutron capture irradiation: setting up a clinical programme in Nice; Irradiation par capture de neutrons: mise en place d`un programme clinique a Nice

    Energy Technology Data Exchange (ETDEWEB)

    Pignol, J.P.; Chauvel, P.; Courdi, A.; Iborra-Brassart, N.; Frenay, M.; Herault, J.; Bensadoun, R.J.; Milano, G.; Demard, F. [Centre de Lutte Contre le Cancer Antoine Lacassagne, 06 - Nice (France); Paquis, P.; Lonjon, M.; Lebrun-Frenay, C.; Grellier, P.; Chatel, M. [Hopital Pasteur, 06 - Nice (France); Nepveu, F.; Patau, J.P. [Toulouse-3 Univ., 31 (France); Breteau, N. [Hopital de la Source, 45 - Orleans (France)

    1996-12-31

    Neutron capture irradiation aims to selectively destroy tumor tumor cell using {sup 10}B(n,{alpha}){sup 7}Li nuclear reactions produced within themselves. Following the capture reaction, an {alpha} particle and a, {sup 7}Li ion are emitted. Carrying an energy of 2.79 MeV, they destroy all molecular structures along their path close to 10 {mu}m. These captures, used exclusively with a `slow` neutron irradiation, provide a neutron capture therapy (BNCT). If they are used in addition to a fast neutron beam irradiation, they provide a neutron capture potentiation (NCP). The Centre Antoine-Lacassagne in Nice is actively involved in the European Demonstration project for BNCT of grade IV glioblastomas (GBM) after surgical excision and BSH administration. Taking into account the preliminary results obtained in Japan, work on an `epithermal` neutron target compatible with various cyclotron beams is in progress to facilitate further developments of this technique. For NCP, thermalized neutron yield has been measured in phantoms irradiated in the fast neutron beam of the biomedical cyclotron in Nice. A thermal peak appears after 5 cm depth in the tissues, delayed after the fast neutron peak at 1.8 cm depth. Thus, a physical overdosage of 10 % may be obtained if 100 ppm of {sup 10}B are assumed in the tissues. Our results using CAL 58 GBM cell line demonstrate a dose modification factor (DMF) of 1.19 when 100 ppm of boric acid are added to the growth medium. Thus for the particles, issued from neutron capture, a biological efficiency at least twice that of fast neutrons can be derived. These results, compared with historical data on fast neutron irradiation of glioblastoma, suggest that a therapeutic window may be obtained for GBM. (author). 26 refs.

  20. Applicability of thermoluminescent dosimeters in X-ray organ dose determination and in the dosimetry of systemic and boron neutron capture radiotherapy

    International Nuclear Information System (INIS)

    Aschan, C.

    1999-01-01

    The main detectors used for clinical dosimetry are ionisation chambers and semiconductors. Thermoluminescent (TL) dosimeters are also of interest because of their following advantages: (i) wide useful dose range, (ii) small physical size, (iii) no need for high voltage or cables, i.e. stand alone character, and (iv) tissue equivalence (LiF) for most radiation types. TL detectors can particularly be used for the absorbed dose measurements performed with the aim to investigate cases where dose prediction is difficult and not as part of a routine verification procedure. In this thesis, the applicability of TL detectors was studied in different clinical applications. Particularly, the major phenomena (e.g. energy dependence, sensitivity to high LET radiation, reproducibility) affecting on the precision and accuracy of TL detectors in the dose estimations were considered in this work. In organ dose determinations of diagnostic X-ray examinations, the TL detectors were found to be accurate within 5% (1 S.D.). For in viva studies using internal irradiation source, i.e. for systemic radiation therapy, a method for determining the absorbed doses to organs was introduced. The TL method developed was found to be able to estimate the absorbed doses to those critical organs near the body surface within 50%. In the mixed neutron-gamma field of boron neutron capture therapy (BNCT), TL detectors were used for gamma dose and neutron fluence measurements. They were found able to measure the neutron dose component with the accuracy of 16%, and therefore to be a useful addition to the activation foils in BNCT neutron dosimetry. The absorbed gamma doses can be measured with TL detectors within 20% in the mixed neutron-gamma field, which enables in viva measurements at BNCT beams with approximately the same accuracy. In this study, the uncertainties of TL dosimeters were found to be high but not essentially greater than those in other measurement techniques used for clinical dosimetry

  1. Development and in vitro testing of liposomal gadolinium-formulations for neutron capture therapy of glioblastoma multiforme

    International Nuclear Information System (INIS)

    Peters, Tanja

    2013-01-01

    For the improvement of current neutron capture therapy, several liposomal formulations of neutron capture agent gadolinium were developed and tested in a glioma cell model. Formulations were analyzed regarding physicochemical and biological parameters, such as size, zeta potential, uptake into cancer cells and performance under neutron irradiation. The neutron and photon dose derived from intracellular as well as extracellular Gd was calculated via Monte Carlo simulations and set in correlation with the reduction of cell survival after irradiation. To investigate the suitability of Gd as a radiosensitizer for photon radiation, cells were also irradiated with synchrotron radiation in addition to clinically used photons generated by linear accelerator. Irradiation with neutrons led to significantly lower survival for Gd-liposome-treated F98 and LN229 cells, compared to irradiated control cells and cells treated with non-liposomal Gd-DTPA. Correlation between Gd-content and -dose and respective cell survival displayed proportional relationship for most of the applied formulations. Photon irradiation experiments showed the proof-of-principle for the radiosensitizer approach, although the photon spectra currently used have to be optimized for higher efficiency of the radiosensitizer. In conclusion, the newly developed Gd-liposomes show great potential for the improvement of radiation treatment options for highly malignant glioblastoma.

  2. Promising cancer treatment modality: the University of California Davis/McClellan Nuclear Radiation Center neutron capture therapy program

    Science.gov (United States)

    Autry-Conwell, Susan A.; Boggan, James E.; Edwards, Benjamin F.; Hou, Yongjin; Vincente, Maria-Graca; Liu, Hungyuan; Richards, Wade J.

    2000-12-01

    Neutron capture therapy (NCT) is a promising new binary therapeutic modality for the treatment of localized tumors. It is accomplished by injection and localization within the tumor of a neutron capture agent (NCA) that alone, is non- toxic. Whenthe tumor is then exposed to neutrons, a relatively non-toxic form of radiation, crytotoxic products are produced that directly or indirectly cause tumor cell death, and yet preserves normal surrounding tissue not contain the NCA. The UC Davis NCT program is currently working to develop and test new compounds or NCA in vitro and in vivo. Many groups worldwide are also working to develop the next generation NCA, but less than five facilities internationally are currently capable to treating clinical brain tumor patients by NCT and only two US facilities, MIT and Brookhaven National Laboratory. In addition to compound development, the UC Davis NCT program is preparing the UC Davis McClellan Nuclear Radiation Center's 2 megawatt TRIGA reactor for NCT clinical trials which would make it the only such facility on the West Coast.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Proposal of a research and development program for cerebral tumor treatment by neutron capture

    International Nuclear Information System (INIS)

    Silva, M.M. da

    1992-01-01

    The researches related to the Boron Neutron Capture Therapy, that were developed at Nuclear Energetic Institute (IPEN/CNEN-SP) and the Coordination for Special Projects (COPESP) are described. A coordinate development program is presented for constructing of an installation, with the purpose of routine utilization of this technique. (C.G.C.)

  5. Induction of chromosomal aberrations by neutron capture reactions

    International Nuclear Information System (INIS)

    Ikushima, Takaji

    1993-01-01

    Boron neutron capture reaction (B-NCR) has been practiced in the treatment of malignancies of the central nervous system and melanoma using a thermal neutron beam from the KUR. Because of the very large neutron absorption cross-section and high kinetic energy released, gadolinium (Gd-157) has been expected to be an another promising element for neutron capture therapy. The dose-response relationship was determined for the induction of chromosomal aberrations by neutron capture reactions by B-10 and Gd-157 in cultured mammalian cells. The cells were exposed to thermal neutron beam with and without B-10 enriched (97 atom %) boric acid or Gd-DTPA, and chromosome-type aberrations were analysed in the first metaphases following irradiation. The frequency of dicentrics and rings increased linearly with neutron fluence either in the presence or absence of B-10 boric acid, while the yield of chromosomal aberrations induced by Gd-NCR increased in a linear quadratic fashion as a function of dose as in γ-rayed cells. Survival curves for the cells exposed to thermal neutrons showed no shoulder irrespective of the loading of B-10, but Gd-NCR produced the survival curve with a small shoulder. The differential chromosomal response to B-NCR and Gd-NCR might reflect the difference in radiation quality generated from the two types of thermal neutron capture reaction. (J.P.N.)

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

    International Nuclear Information System (INIS)

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

    2000-01-01

    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

  7. Radiosensitivity of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction.

    Science.gov (United States)

    Masunaga, S; Sakurai, Y; Tanaka, H; Hirayama, R; Matsumoto, Y; Uzawa, A; Suzuki, M; Kondo, N; Narabayashi, M; Maruhashi, A; Ono, K

    2013-01-01

    To detect the radiosensitivity of intratumour quiescent (Q) cells unlabelled with pimonidazole to accelerated carbon ion beams and the boron neutron capture reaction (BNCR). EL4 tumour-bearing C57BL/J mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumour proliferating (P) cells. After the administration of pimonidazole, tumours were irradiated with γ-rays, accelerated carbon ion beams or reactor neutron beams with the prior administration of a (10)B-carrier. Responses of intratumour Q and total (P+Q) cell populations were assessed based on frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of pimonidazole-unlabelled tumour cells was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. Following γ-ray irradiation, the pimonidazole-unlabelled tumour cell fraction showed significantly enhanced radiosensitivity compared with the whole tumour cell fraction, more remarkably in the Q than total cell populations. However, a significantly greater decrease in radiosensitivity in the pimonidazole-unlabelled cell fraction, evaluated using a delayed assay or a decrease in radiation dose rate, was more clearly observed among the Q than total cells. These changes in radiosensitivity were suppressed following carbon ion beam and neutron beam-only irradiaton. In the BNCR, the use of a (10)B-carrier, especially L-para-boronophenylalanine-(10)B, enhanced the sensitivity of the pimonidazole-unlabelled cells more clearly in the Q than total cells. The radiosensitivity of the pimonidazole-unlabelled cell fraction depends on the quality of radiation delivered and characteristics of the (10)B-carrier used in the BNCR. The pimonidazole-unlabelled subfraction of Q tumour cells may be a critical target in tumour control.

  8. A tool for preparation of voxel phantoms. Potentialities for planning of neutron capture therapy

    International Nuclear Information System (INIS)

    Borisov, Nikolay; Khokhlov, Vyacheslav; Kulakov, Viktor; Sheino, Igor; Carlan, L. de; Franck, Didier

    2006-01-01

    The tremendous development of voxel phantom techniques for computations in nuclear medicine and hygiene during the past decade led to the creation of special software packages designed for automatic preparation of voxel phantoms for subsequent radiation transport calculations. The package OEDIPE, which facilitates the MCNP (X) calculations, was originally designed for internal irradiation dosimetry. However, its flexibility and universality makes it attractive for radiation therapy planning, too. (author)

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

    Science.gov (United States)

    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.

  10. Quantitative analysis of proton boron fusion therapy (PBFT) in various conditions

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Joo-Young; Yoon, Do-Kun; Suh, Tae Suk [College of Medicine, Catholic University of Korea, Seoul (Korea, Republic of)

    2015-05-15

    From the theoretical point of view, the PBFT has some strong advantages over currently existing radiotherapy methods. First, boron-based tumor targeting is required prior to performing the treatments such as boron-neutron capture therapy (BNCT). Tumor targeting should be performed before the BNCT by injecting the boronate compound. If boron is not taken up by the normal tissue, the normal tissue can be spared the irradiation by alpha particles. When boron uptake occurs in the target region, selective therapy is possible by neutron capture reaction of labeled boron particles in the target region. Likewise, when boron is distributed in the tumor region for the PBFT, the proposed method can represent a more critical discriminative therapy than either the BNCT or conventional particle therapy. In the conventional proton therapy, in order to deliver a dose to a tumor, the proton beam energy has to be adjusted along the tumor region (e.g., shape and depth). The proton therapy aims at delivering the maximal dose to the tumor by using protons only. In this study, the effectiveness of the PBFT with respect to several physical parameters was evaluated quantitatively by using Monte Carlo simulations. We confirmed that the PBFT can be used to perform critical discriminative therapy. Also, the results of our studies can be used for constructing the PFBT dose database that can be utilized in treatment planning systems (TPSs)

  11. In vivo evaluation of the 3-carboranyl thymidine analogue (3-CTA), N5-2OH, for neutron capture therapy

    International Nuclear Information System (INIS)

    Barth, Rolf F.; Yang, Weilian; Wu, Gong; Byun, Youngjoo; Tjarks, Werner; Eriksson, Staffan; Binns, Peter J.; Riley, Kent J.

    2006-01-01

    The purpose of the present study was to evaluate a 3 CTA, designated N5-2OH, as a boron delivery agent for NCT. Target validation was established using the thymidine kinase 1 (+) wild type L929 cell line and its TK1(-) counterpart, which were implanted subcutaneously into NIH nu/nu mice. 10 B-enriched N5-2OH, solubilized in DMSO (50μg 10 B in 15μl), was administered by 2 intratumoral (i.t.) injections at 2 h intervals. Two hours later the animals were irradiated at the MITR-II Research Reactor, following which tumor volumes were determined over a period of 30 days. Mice bearing TK1(+) wild type tumors, which had received N5-2OH, had a 15 fold inhibition in tumor growth compared to TK1(-) controls (247 versus 3,603 mm 3 ). Based on these data, biodistribution and therapy studies were initiated in F98 glioma bearing rats. Animals received 500μg of N5-2OH, administered intracerebrally (i.c.) by convection enhanced delivery (CED) using ALZET pumps (8μl/h for 24 h). The tumor boron concentration was 17.3μg/g compared to undetectable amounts in normal brain and blood. BNCT was carried out 14 d following i.c. implantation of 10 3 F98 glioma cells and 24 h following CED of N5-2OH (500μg/200μl). The mean survival time (MST) of these animals was 38 d compared to 31 d and 25 d, respectively, for irradiated and untreated controls. Studies are planned to optimize the delivery and formulation of N5-2OH and additional therapy studies will be carried out using N5-2OH in combination with BPA and BSH. (author)

  12. Investigation for the extended application of melanoma Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1991-11-01

    This issue is the Part B of the Progress Report (III) which includes our latest research results focusing mainly on the successful treatment of the first human melanoma patient who had metastasis in the scalp region. We also include the subsequent clinical treatment of various types of human primary melanoma lesions and the additional basic investigations necessary to perform the treatment. (J.P.N.)

  13. Collimator and shielding design for boron neutron capture therapy (BNCT) facility at TRIGA MARK II reactor

    International Nuclear Information System (INIS)

    Mohd Rafi Mohd Solleh; Abdul Aziz Tajuddin; Abdul Aziz Mohamed; Eid Mahmoud Eid Abdel Munem; Mohamad Hairie Rabir; Julia Abdul Karim; Yoshiaki, Kiyanagi

    2011-01-01

    The geometry of reactor core, thermal column, collimator and shielding system for BNCT application of TRIGA MARK II Reactor were simulated with MCNP5 code. Neutron particle lethargy and dose were calculated with MCNPX code. Neutron flux in a sample located at the end of collimator after normalized to measured value (Eid Mahmoud Eid Abdel Munem, 2007) at 1 MW power was 1.06 x 10 8 n/ cm 2 / s. According to IAEA (2001) flux of 1.00 x 10 9 n/ cm 2 / s requires three hours of treatment. Few modifications were needed to get higher flux. (Author)

  14. Calculations of neutron source at the KYIV research reactor for the boron neutron capture therapy aims

    International Nuclear Information System (INIS)

    Gritzay, O.; Kalchenko, O.; Klimova, N.; Razbudey, V.; Sanzhur, A.

    2006-01-01

    Calculation results of an epithermal neutron source which can be created at the Kyiv Research Reactor (KRR) by means of placing of specially selected moderators, filters, collimators, and shielding into the 10-th horizontal experimental tube (so-called thermal column) are presented. The general Monte-Carlo radiation transport code MCNP4C [1], the Oak Ridge isotope generation code ORIGEN2 [2] and the NJOY99 [3] nuclear data processing system have been used for these calculations

  15. Boron neutron capture therapy for the treatment of oral cancer in the hamster cheek pouch model

    International Nuclear Information System (INIS)

    Kreimann, Erica L.; Itoiz, Maria E.; Schwint, Amanda E.; Longhino, Juan; Blaumann, Herman; Calzetta, Osvaldo

    2003-01-01

    We have proposed and validated the hamster cheek pouch model of oral cancer for BNCT studies separately. We herein report the first evidence of the usefulness of BNCT for the treatment of oral cancer in an experimental model. We assessed the response of hamster cheek pouch tumors, precancerous tissue and normal oral tissue to BPA-mediated BNCT employing the thermalized epithermal beam of the RA-6 Reactor at the Bariloche Atomic Center. BNCT leads to complete remission by 15 days post-treatment in 78% of tumors and partial remission in a further 13% of tumors with virtually no damage to normal tissue. (author)

  16. Feasibility study of SPECT system for online dosimetry imaging in boron neutron capture therapy.

    Science.gov (United States)

    Hales, B; Katabuchi, T; Hayashizaki, N; Terada, K; Igashira, M; Kobayashi, T

    2014-06-01

    A single collimator version of a proposed PG-SPECT system was manufactured and experimentally tested. Combining this experimental data with Monte Carlo simulation, the viability of Ge and CdTe semiconductors detectors was calculated. It was determined that the best detector of the ones compared would be a CdTe detector of 2-3mm, aided by the benefit of adding a Compton-suppression anti-coincidence timing detector. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Czech Academy of Sciences Publication Activity Database

    Binns, P. J.; Riley, K. J.; Harling, O. K.; Kiger III, 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.; Spurný, František

    2005-01-01

    Roč. 32, č. 12 (2005), s. 3729-3736 ISSN 0094-2405 R&D Projects: GA ČR GA202/04/0795 Institutional research plan: CEZ:AV0Z10480505 Keywords : BNCT * thermal neutrons * dosimetry intercomparison Subject RIV: BO - Biophysics Impact factor: 3.192, year: 2005

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

    Energy Technology Data Exchange (ETDEWEB)

    Chadha, M. [Beth Israel Medical Center, NY (United States). Dept. of Radiation Oncology; Coderre, J.A.; Chanana, A.D. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1996-12-31

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

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

    International Nuclear Information System (INIS)

    Chadha, M.

    1996-01-01

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

  20. Effects of secondary interactions on the dose calculation in treatments with Boron Neutron Capture Therapy (BNCT)

    International Nuclear Information System (INIS)

    Monteiro, E.

    2004-01-01

    The aimed of this work consists of evaluating the influence of the secondary contributions of dose (thermal neutrons dose, epithermal neutrons dose, fast neutrons dose and photon dose) in treatment planning with BNCT. MCNP4B Code was used to calculate RBE-Gy doses through the irradiation of the modified Snyder head head phantom.A reduction of the therapeutical gain of monoenergetic neutron beans was observed in non invasive treatments, provoked for the predominance of the fast neutron dose component in the skin, showing that the secondary contributions of dose can contribute more in the direction to raise the dose in the fabric healthy that in the tumor, thus reducing the treatment efficiency. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Ackermann, A.L. (ed.)

    1990-10-01

    This bulletin discusses activities during this reporting period in the areas of: supporting technology development; large animal model studies; melanoma project; human studies; stability, pharmacology, and toxicology of drugs; and PBF technical support. (FL)

  2. Development of a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

    Science.gov (United States)

    Kreiner, A J; Castell, W; Di Paolo, H; Baldo, M; Bergueiro, J; Burlon, A A; Cartelli, D; Vento, V Thatar; Kesque, J M; Erhardt, J; Ilardo, J C; Valda, A A; Debray, M E; Somacal, H R; Sandin, J C Suarez; Igarzabal, M; Huck, H; Estrada, L; Repetto, M; Obligado, M; Padulo, J; Minsky, D M; Herrera, M; Gonzalez, S J; Capoulat, M E

    2011-12-01

    We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Boron neutron capture therapy for an explanted organ: The logistical challenges

    International Nuclear Information System (INIS)

    Wittig, A.; Moss, R.; Kaiser, G.M.; Malago, M.; Nievaart, V.; Sauerwein, W.A.

    2009-01-01

    Single liver metastases of colorectal cancer can be cured by surgery; disseminated liver metastases are incurable. A research group in Pavia, Italy, used BNCT as an experimental method to irradiate in curative intention the explanted liver of patients suffering from disseminated hepatic metastases. The situation in Pavia, where a reactor with a specially adapted thermal column and the hospital are close by, is unique. For the purpose of the present study, it was necessary to investigate how the Pavia experience can be repeated with transplantation centers located at distance from a reactor. Some basic investigations of the logistics of such a procedure are reported.

  4. In vitro studies of the cellular response to boron neutron capture therapy (BNCT) in thyroid carcinoma

    International Nuclear Information System (INIS)

    Rodriguez, C; Carpano, M; Perona, M; Thorp, S; Curotto, P; Pozzi, E; Casal, M; Juvenal, G; Pisarev, M; Dagrosa, A

    2012-01-01

    Background: Previously, we have started to study the mechanisms of DNA damage and repair induced by BNCT in thyroid carcinoma some years ago. We have shown different genotoxic patterns for tumor cells irradiated with gamma rays, neutrons alone or neutrons plus different compounds, boronophenylalanine (BPA) or α, β - dihydroxyethyl)-deutero-porphyrin IX (BOPP). In the present study we analyzed the expression of Ku70, Rad51 and Rad54 components of non homologous end-joing (NHEJ) and homologous recombination repair (HRR) pathways, respectively, induced by BNCT in human cells of thyroid carcinoma. Methods: A human cell line of follicular thyroid carcinoma (WRO) in exponential growth phase was distributed into the following groups: 1) Gamma Radiation, 2) Radiation with neutrons beam (NCT), 3) Radiation with n th in presence of BPA (BNCT). A control group for each treatment was added. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux= 1.10 10 n/cm 2 sec) or with a source of 60 Co. The irradiations were performed during different lapses in order to obtain a total physical dose of 3 Gy (±10%). The mRNA expressions of Ku70, Rad 51 and Rad 54 were analysed by reverse transcription-polymerase chain reaction (RT-PCR) at different times post irradiation (2, 4, 6, 24 and 48 h). DNA damage was evaluated by immunofluorescence using an antibody against the phosphorylation of histone H2AX, which indicates double strand breaks in the DNA. Results: The expression of Rad51 increased at 2 h post-irradiation and it lasted until 6 h only in the neutron and neutron + BPA groups (p<0.05). Rad54 showed an up-regulation from 2 to 24 h in both groups irradiated with the neutron beam (with and without BPA) (p<0.05). On the other hand, Ku70 mRNA did not show a modification of its expression in the irradiated groups respect to the control group. Conclusion: these results would indicate an activation of the HRR pathway in the thyroid carcinoma cells treated by BNCT. Ku70 genetic expression was not modified suggesting an effect either at the translation or by inhibiting protein degradation. The knowledge of repair mechanisms will allow to manipulate the tumor response to the irradiation (author)

  5. Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: An assessment of clinical potential

    Energy Technology Data Exchange (ETDEWEB)

    Hopewell, J.W., E-mail: john.hopewell@gtc.ox.ac.uk [Green Templeton College and Particle Therapy Cancer Research Institute, University of Oxford, Oxford (United Kingdom); Gorlia, T. [Data Center, EORTC, Brussels (Belgium); Pellettieri, L. [Hammercap Medical AB, Stockholm (Sweden)] [Department of Neurosurgery, Goeteborg University, Goeteborg (Sweden); Giusti, V. [Hammercap Medical AB, Stockholm (Sweden)] [Department of Mechanical, Nuclear and Production Engineering, University of Pisa, Pisa (Italy); H-Stenstam, B. [Nykoeping Hospital, County of Sormland (Sweden); Skoeld, K. [Hammercap Medical AB, Stockholm (Sweden)

    2011-12-15

    The purpose of this analysis was to assess the potential of BNCT, with L-boronophenylalanine (L-BPA), as first line radiotherapy for glioblastoma multiforme (GBM). The survival of patients with newly diagnosed GBM from a phase II BNCT study was compared with those from the two arms of a phase III study with conventional radiotherapy (RT) vs. RT plus concomitant and adjuvant medication with temozolomide (TMZ). A small subgroup, for which the methylation status of the O{sup 6}-methylguanine-DNA methyltransferase (MGMT) DNA-repair gene was known, was also considered. The results indicated that the use of BNCT with BPA should be explored in a stratified randomized phase II trial in which patients with the unmethylated MGMT DNA-repair gene are offered BNCT vs. RT plus TMZ.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ackermann, A.L. (ed.); Dorn, R.V. III.

    1990-09-01

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

  7. Development of a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kreiner, A.J., E-mail: kreiner@tandar.cnea.gov.ar [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin (Argentina)] [CONICET, Buenos Aires (Argentina); Castell, W. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina); Di Paolo, H. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin (Argentina); Baldo, M. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina); Bergueiro, J. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina)] [CONICET, Buenos Aires (Argentina)

    2011-12-15

    We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the {sup 7}Li(p,n){sup 7}Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas.

  8. Direct thermal neutron capture

    International Nuclear Information System (INIS)

    Raman, S.; Kahane, S.; Lynn, J.E.

    1987-01-01

    We discuss the direct-capture theory pertaining to primary electric dipole (E1) transitions following slow-neutron capture. For light nuclides that we have studied (including 9 Be, 12 C, 13 C, 24 Mg, 25 Mg, 26 Mg, 32 S, 33 S, 34 S, 40 Ca, and 44 Ca), estimates of direct-capture cross sections using optical-model potentials with physically realistic parameters, are in reasonable agreement with the data. Minor disagreements that exist are consistent with extrapolations to light nuclides of generally accepted formulations of compound-nucleus capture. We also discuss the channel-capture approximation which is, in general, a good representation of these cross sections in heavier nuclei particularly if the scattering lengths are not different from the corresponding potential radii. We also draw attention to cases where the use of this formula leads to inaccurate predictions. 9 refs., 1 fig., 2 tab

  9. Biodistribution of BPA and BSH after single, repeated and simultaneous administrations for neutron-capture therapy of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ichikawa, H. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan)], E-mail: ichikawa@pharm.kobegakuin.ac.jp; Taniguchi, E. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fukumori, Y. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan)

    2009-07-15

    The effect of administration mode of L-BPA and BSH on the biodistribution in the melanoma-bearing hamsters was investigated. In single intravenous (i.v.) administration, BSH (100 mg BSH/kg) showed no significant retention of {sup 10}B in all the tissues, including tumors, while long-term retention of {sup 10}B in the tumor, muscle and brain was observed with L-BPA (500 mg BPA/kg). The dose escalation of L-BPA and the simultaneous single administration of L-BPA and BSH were not so effective at increasing boron accumulation in tumor after bolus i.v. injection. The boron concentration in tumor was 41 {mu}g B/g after single bolus i.v. injection even at the dose of 1000 mg BPA/kg. In contrast, two sequential bolus i.v. injections of L-BPA with the dose of 500 mg BPA/kg each was found to be effective at increasing {sup 10}B accumulation in the tumor; the maximum {sup 10}B concentration in the tumor reached 52 {mu}g B/g at 3 h after the second i.v. injection.

  10. A test-type hyper-thermal neutron generator for neutron capture therapy - estimation of neutron energy spectrum by simulation calculations and TOF experiments

    International Nuclear Information System (INIS)

    Sakurai, Yoshinori; Kobayashi, Tooru; Kobayashi, Katsuhei

    1999-01-01

    In order to clarify the irradiation characteristics of hyper-thermal neutrons and the feasibility of a hyper-thermal neutron irradiation field for neutron capture therapy, a 'test-type' hyper-thermal neutron generator was designed and made. Graphite of 6 cm thickness and 21 cm diameter was selected as the high temperature scatterer. The scatterer is heated up to 1200 deg. C maximum using molybdenum heaters. The radiation heat is shielded by reflectors of molybdenum and stainless steel. The temperature is measured using three R-type thermo-couples and controlled by a program controller. The total thickness of the generator is designed to be as thin as possible, 20 cm in maximum, in the standing point of the neutron beam intensity. The thermal stability, controllability and safety of the generator at high temperature employment were confirmed by the heating tests. As one of the experiments for the characteristics estimation, the neutron energy spectrum dependent on the scatterer temperature was measured by the TOF (time of flight) method using the LINAC neutron generator. The estimations by simulation calculations were also performed. From the experiment and calculation results, it was confirmed that the neutron temperature shifted higher as the scatterer temperature was higher. The prospect of the feasibility of the 'hyper-thermal neutron irradiation field for NCT' was opened from the estimation results of the generator characteristics by the simulation calculations and experiments

  11. Gd-C{sub 82} metallofullerenes for neutron capture therapy-fullerene solubilization by poly(ethylene glycol)-block-poly(2-(N, N-diethylamino)ethyl methacrylate) and resultant efficacy in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Yukichi; Kudo, Shinpei; Nagasaki, Yukio, E-mail: yukio@ims.tsukuba.ac.jp [Graduate School of Pure and Applied Sciences University of Tsukuba, Ten-noudai 1-1-1, Tsukuba, Ibaraki 305-8573 (Japan)

    2011-08-15

    Poly(ethylene glycol)-block-poly(2-(N,N-diethylamino)ethyl methacrylate) (PEG-b-PAMA) was found to solubilize fullerenes such as C{sub 60}, and this technique was applied to metallofullerenes. Gd-C{sub 82} was easily dissolved in water in the presence of PEG-b-PAMA without any covalent derivatization, forming a transparent complex about 20-30 nm in diameter. Low cytotoxicity was confirmed in vitro. Neutron irradiation of cultured cells (colon-26 adenocarcinoma) with Gd-C{sub 82}-PEG-b-PAMA-complexed nanoparticles showed effective cytotoxicity, indicating the effective emission of gamma rays and internal conversion electrons produced from the neutron capture reaction of Gd. This result suggests a potentially valuable approach to gadolinium-based neutron capture therapy.

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

    International Nuclear Information System (INIS)

    Holden, N.E.

    1981-01-01

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

  13. Monte Carlo simulation of proton boron fusion reaction for radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Mi; Yoon, Do Kun; Suh, Tae Suk [Catholic University of Korea, Seoul (Korea, Republic of)

    2016-05-15

    The principle of the proton boron fusion therapy (PBFT) is based on this reaction as the radiation therapy technique. First, because three alpha particles can contribute to the death of the tumor cell by the use of one proton, high therapy efficiency can be achieved by using smaller flux than conventional proton therapy or the boron neutron capture therapy (BNCT), after the thermal neutron was captured by the labeled boron in the tumor region, an alpha particle is emitted from the capture reaction point. An alpha particle induces the death of the tumor cell by the one capture reaction. However, three alpha particles are emitted from the point of the proton boron fusion reaction. If this reaction is applied to the radiation therapy, the therapy results could be more effective in inducing the death of tumor cells using a smaller flux. In addition, the proton's energy loss during its propagation through matter is described by the Bragg-peak. After the boron-labeled compound is accumulated in the tumor region, if the portion of the proton's maximum dose (Bragg-peak) is included at the tumor region, which is the boron uptake region (BUR), a dramatic therapy effect with less damage to normal tissue can be expected. This study was performed to introduce a therapy method using the proton boron fusion reaction and verify the theoretical validity of PBFT using Monte Carlo simulations. In this study, there are two parts of the simulation to confirm the validity of PBFT. First, the variation of the Bragg-peak of the proton depending on the location of the BUR was examined. The other simulation was performed to confirm the existence of the prompt gamma ray peak of 719 keV from energy spectrum simulation. PBFT method is still at the conceptual stage, the verification of its effectiveness is required for the use of a physical approach.

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

    Science.gov (United States)

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

    2010-11-01

    HeLa cells were incubated with neutron capture nuclei (boron-10 and gadolinium)-containing carbon nanoparticles, followed by irradiation of slow thermal neutron beam. Under a neutron flux of 6 x 10(11) n/cm(2) (or 10 min irradiation at a neutron flux of 1 x 10(9) n/cm(2) s), the percentages of acute cell death at 8 h after irradiation are 52, 55, and 28% for HeLa cells fed with BCo@CNPs, GdCo@CNPs, and Co@CNPs, respectively. The proliferation capability of the survived HeLa cells was also found to be significantly suppressed. At 48 h after neutron irradiation, the cell viability further decreases to 35 +/- 5% as compared to the control set receiving the same amount of neutron irradiation dose but in the absence of carbon nanoparticles. This work demonstrates "proof-of-concept" examples of neutron capture therapy using (10)B-, (157)Gd-, and (59)Co-containing carbon nanoparticles for effective destruction of cancer cells. It will also be reported the preparation and surface functionalization of boron or gadolinium doped core-shell cobalt/carbon nanoparticles (BCo@CNPs, GdCo@CNPs and Co@CNPs) using a modified DC pulsed arc discharge method, and their characterization by various spectroscopic measurements, including TEM, XRD, SQUID, FT-IR, etc. Tumor cell targeting ability was introduced by surface modification of these carbon nanoparticles with folate moieties. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  15. Complexion of Boric Acid with 2-Deoxy-D-glucose (DG) as a novel boron carrier for BNCT

    OpenAIRE

    Akan, Zafer; Demiroglu, Hasan; Avcibasi, Ugur; Oto, Gokhan; Ozdemir, Hulya; Deniz, Sabahattin; Basak, Ali Sadi

    2014-01-01

    Objective: Boron neutron capture therapy (BNCT) is an intensive research area for cancer researchers. Especially the side effects and inabilities of conventional therapies in some cases, directs researchers to find out a new cancer therapy methods such as BNCT. One of three important problem of BNCT is targeting of boron to tumor tissue. Borono Phenyl Alanine (BPA) and Borono Sodium Borocaptate (BSH) are already using in clinical studies as boron carriers. New boron carriers are searching fo...

  16. Synovectomy by Neutron capture; Sinovectomia por captura de neutrones

    Energy Technology Data Exchange (ETDEWEB)

    Vega C, H.R.; Torres M, C. [Centro Regional de Estudios Nucleares, Universidad Autonoma de Zacatecas, C. Cipres 10, Fracc. La Penuela, 98000 Zacatecas (Mexico)

    1998-12-31

    The Synovectomy by Neutron capture has as purpose the treatment of the rheumatoid arthritis, illness which at present does not have a definitive curing. This therapy requires a neutron source for irradiating the articulation affected. The energy spectra and the intensity of these neutrons are fundamental since these neutrons induce nuclear reactions of capture with Boron-10 inside the articulation and the freely energy of these reactions is transferred at the productive tissue of synovial liquid, annihilating it. In this work it is presented the neutron spectra results obtained with moderator packings of spherical geometry which contains in its center a Pu{sup 239} Be source. The calculations were realized through Monte Carlo method. The moderators assayed were light water, heavy water base and the both combination of them. The spectra obtained, the average energy, the neutron total number by neutron emitted by source, the thermal neutron percentage and the dose equivalent allow us to suggest that the moderator packing more adequate is what has a light water thickness 0.5 cm (radius 2 cm) and 24.5 cm heavy water (radius 26.5 cm). (Author)

  17. Application of 10B entrapped PEG-liposome to boron neutron-capture therapy for pancreatic cancer model in vivo

    International Nuclear Information System (INIS)

    Yanagie, H.; Eriguchi, M.; Maruyama, K.; Takizawa, T.; Ishida, O.; Ogura, K.; Matsumoto, T.; Sakurai, Y.; Kobayashi, T.; Ono, K.; Rant, J.; Skvarc, J.; Ilic, R.; Shinohara, A.; Chiba, M.; Kobayashi, H.

    1999-01-01

    The cytotoxic effects for tumor were evaluated with intravenous injection 10 B PEG-liposome (Stealth liposome) on human pancreatic carcinoma wenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with 10 B bare-liposome or 10 B PEG liposome, AsPC-1 tumour growth was suppressed relative to controls. Injection of 10 B PEG-liposome caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of 10 B PEG-liposome can increase the retention of 10 B atoms by tumor cells, causing tumor growth suppression in vivo upon thermal neutron irradiation.(author)

  18. Compact D-D Neutron Source-Driven Subcritical Multiplier and Beam-Shaping Assembly for Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Ganda, Francesco; Vujic, Jasmina; Greenspan, Ehud; Leung, Ka-Ngo

    2010-01-01

    This work assesses the feasibility of using a small, safe, and inexpensive keff 0.98 subcritical fission assembly [subcritical neutron multiplier (SCM)] to amplify the treatment neutron beam intensity attainable from a compact deuterium-deuterium (D-D) fusion neutron source delivering [approximately]1012 n/s. The objective is to reduce the treatment time for deep-seated brain tumors to [approximately]1 h. The paper describes the optimal SCM design and two optimal beam-shaping assemblies (BSAs) - one designed to maximize the dose rate and the other designed to maximize the total dose that can be delivered to a deep-seated tumor. The neutron beam intensity amplification achieved with the optimized SCM and BSA results in an increase in the treatment dose rate by a factor of 18: from 0.56 Gy/h without the SCM to 10.1 Gy/h. The entire SCM is encased in an aluminum structure. The total amount of 20% enriched uranium required for the SCM is 8.5 kg, and the cost (not including fabrication) is estimated to be less than $60,000. The SCM power level is estimated at 400 W when driven by a 1012 n/s D-D neutron source. This translates into consumption of only [approximately]0.6% of the initially loaded 235U atoms during 50 years of continuous operation and implies that the SCM could operate continuously for the entire lifetime of the facility without refueling. Cooling the SCM does not pose a challenge; it may be accomplished by natural circulation as the maximum heat flux is only 0.034 W/cm2.

  19. Dose Determination using alanine detectors in a Mixed Neutron and Gamma Field for Boron Neutron Capture Therapy of Liver Malignancies

    DEFF Research Database (Denmark)

    Schmitz, T.; Blaickner, M.; Ziegner, M.

    2011-01-01

    be suitable for measurements in mixed neutron and gamma fields. Materials and Methods Two experiments have been carried out in the thermal column of the TRIGA Mark II reactor at the University of Mainz. Alanine dosimeters have been irradiated in a phantom and in liver tissue. Results For the interpretation......, in combination with flux measurements and Monte Carlo calculations with FLUKA, suggest that it is possible to establish a system for monitoring the dose in a mixed neutron and gamma field for BNCT and other applications in radiotherapy....

  20. Application of 10BSH entrapped transferrin-PEG-liposome to boron neutron-capture therapy (BNCT) for solid tumor

    International Nuclear Information System (INIS)

    Maruyama, K.; Ishida, O.; Iwatsuru, M.; Yanagie, H.; Eriguchi, M.; Kobayashi, H.

    2000-01-01

    The successful treatment of cancer by BNCT requires the selective concentration of 10 B within malignant tumor cells. Intracellular targeting ability and cytotoxic effects of 10 B entrapped TF-PEG-liposomes, in which TF is covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes, were examined in Colon 26 tumor-bearing mice. TF-PEG-liposomes readily bound to tumor cells in vivo, and were internalized by receptor-mediated endocytosis. 10 B-PEG-liposomes and 10 B-TF-PEG-liposomes showed prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue and reached high level of 10 B content in tumor. After thermal neutron irradiation of mice injected with 10 B-PEG-liposomes or 10 B-TF-PEG-liposome, tumor growth was suppressed relative to controls. These results suggest that intravenous injection of 10 B TF-PEG-liposome can increase the intracellular retention of 10 B atoms, which were introduced by receptor mediated endocytosis after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. (author)

  1. Acute and late reactions following boron neutron capture epithermal-neutron therapy in dogs with spontaneous brain tumors

    International Nuclear Information System (INIS)

    Gavin, P.R.; DeHaan, C.E.; Kraft, S.L.; Moore, M.P.; Wendling, L.R.; Dorn, R.V. III.

    1992-01-01

    Dogs have a relatively high incidence of primary tumors of the central nervous system and have proven to be good models for new therapeutic investigation. The pharmacokinetics of borocaptate sodium have been well documented in the dog. Preliminary investigations of the normal tissue tolerance and was designed to ensure a therapeutic margin was present for the dogs with spontaneous tumors; i.e., a measurable effect could be had on the tumor at doses considered safe for the normal tissues

  2. Accelerator tube construction and characterization for a tandem-electrostatic-quadrupole for accelerator-based boron neutron capture therapy.

    Science.gov (United States)

    Cartelli, D; Vento, V Thatar; Castell, W; Di Paolo, H; Kesque, J M; Bergueiro, J; Valda, A A; Erhardt, J; Kreiner, A J

    2011-12-01

    The accelerator tubes are essential components of the accelerator. Their function is to transport and accelerate a very intense proton or deuteron beam through the machine, from the ion source to the neutron production target, without significant losses. In this contribution, we discuss materials selected for the tube construction, the procedures used for their assembly and the testing performed to meet the stringent requirements to which it is subjected. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Factors interfering with comparison of radiation doses to GBM patients treated with boron neutron capture therapy at Petten and Brookhaven

    International Nuclear Information System (INIS)

    Vliet-Vroegindeweij, Corine van; Huiskamp, Rene; Capala, Jacek; Diaz, A.Z.; Sauerwein, Wolfgang

    2000-01-01

    The current clinical trials on BNCT in Japan, Europe and the USA have adapted their own, individual set of definitions used for treatment planning. As a result the reported doses are not directly comparable and the differences should be considered separately. This article summarises the effects of these differences between the protocols used in Petten and at BNL. (author)

  4. B-decachloro-o-carborane derivatives as suitable boron carriers for the preparation of water-soluble boron-conjugated macromolecules

    International Nuclear Information System (INIS)

    Gabel, D.; Walczyna, R.; Wellmann, F.; Riesenberg, H.; Hocke, I.

    1982-01-01

    The preparation of boron-containing macromolecules, especially immunoglobulins, for boron neutron capture therapy, has so far been rather unsuccessful, because of the increased water insolubility of heavily substituted proteins. By using polar boron compounds, some of the difficulties previously encountered in the preparation of boron-conjugated immunoglobulins might be overcome. To this end, the authors have investigated the use of B-decachloro-o-carborane (B 10 Cl 10 C 2 H 2 ) for the preparation of water-soluble macromolecules

  5. Adjustment methodology for preliminary study on the distribution of bone tissue boron. Potential therapeutic applications

    International Nuclear Information System (INIS)

    Brandizzi, D; Dagrosa, A; Carpano, M.; Olivera, M. S.; Nievas, S; Cabrini, R.L.

    2013-01-01

    Boron is an element that has an affinity for bone tissue and represents a considered element in bone health . Other boron compounds are used in the Boron Neutron Capture Therapy (BNCT ) in the form of sodium borocaptate (BSH ) and borono phenylalanine (BPA). The results of clinical trials up to date are encouraging but not conclusive . At an experimental level , some groups have applied BNCT in osteosarcomas . We present preliminary methodological adjustments for the presence of boron in bone. (author)

  6. The coordination chemistry of boron porphyrin complexes B2OX2 ...

    Indian Academy of Sciences (India)

    Unknown

    therapeutic method that utilizes porphyrin deriva- tives localized in tumors, as in situ photosensitizers for the production of singlet oxygen on irradiation with red light.2 Candidate porphyrin derivatives that contain boron for boron neutron capture therapy (BNCT) ... in small animal glioma models.4,5 BNCT is a two-step.

  7. Neutron capture therapy (NCT) and in-hospital neutron irradiator (IHNI) a new technology on binary targeting radiation therapy of cancer

    International Nuclear Information System (INIS)

    Zhou Yongmao

    2009-01-01

    BNCT is finally becoming 'a new option against cancer'. The difficulties for its development progress of that firstly is to improve the performance of boron compounds,secondly, it is the requirements of quantification and accuracy upon radiation dosimetry evaluation in clinical trials. Furthermore, that is long anticipation on hospital base neutron sources. It includes dedicated new NCT reactor, accelerator based neutron sources, and isotope source facilities. In addition to reactors, so far, the technology of other types of sources for clinical trials is not yet completely proven. The In-Hospital Neutron Irradiator specially designed for NCT, based on the MNSR successfully developed by China, can be installed inside or near the hospital and operated directly by doctors. The Irradiator has two neutron beams for respective treatment of the shallow and deep tumors. It is expected to initiate operation in the end of this year. It would provide a safe, low cost, and effective treatment tool for the NCT routine application in near future. (authors)

  8. Neutron capture by hook or by crook

    Science.gov (United States)

    Mosby, Shea

    2016-03-01

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

  9. Use of neutron-capture plastic fibers for nondestructive assay

    Energy Technology Data Exchange (ETDEWEB)

    Heger, A.S.; Grazioso, R.F.; Mayo, D.R.; Ensslin, N.; Miller, M.C.; Huang, H.Y.; Russo, P.A.

    1998-12-31

    Neutron-capture plastic fibers can be used as a nondestructive assay tool. The detectors consist of an active region assembled from ribbons of boron-({sup 10}B) loaded optical fibers. The mixture of the moderator and thermal neutron absorber in the fiber yields a detector with high efficiency ({var_epsilon}) and a short die-away time ({tau}). The deposited energy of the resultant charged particles is converted to light that is collected by photomultiplier tubes mounted at both ends of the fiber. Thermal neutron coincidence counters (TNCC) made of these fibers can serve to verify fissile materials generated from the nuclear fuel cycle. This type of detector may extend the range of materials now accessible to assay by {sup 3}He detectors. Experiments with single fibers of diameters 0.25, 0.50, and 1.00 mm test their ability to distinguish between the signals generated from neutron interactions and those from gamma rays. These results are compared with those obtained from simulation analyses for the same purpose. Light output and attenuation, neutron detection efficiency, and the signal-to-noise ratios of these fibers have also been investigated. The experimental results for light attenuation and neutron detection efficiency are consistent with the values obtained from simulation studies. A comparison of the performance of various configurations of the plastic scintillating fibers with that of other neutron-capture devices such as {sup 3}He detectors is also discussed.

  10. Neutron capture cross sections of Kr

    Science.gov (United States)

    Fiebiger, Stefan; Baramsai, Bayarbadrakh; Couture, Aaron; Krtička, Milan; Mosby, Shea; Reifarth, René; O'Donnell, John; Rusev, Gencho; Ullmann, John; Weigand, Mario; Wolf, Clemens

    2018-01-01

    Neutron capture and β- -decay are competing branches of the s-process nucleosynthesis path at 85Kr [1], which makes it an important branching point. The knowledge of its neutron capture cross section is therefore essential to constrain stellar models of nucleosynthesis. Despite its importance for different fields, no direct measurement of the cross section of 85Kr in the keV-regime has been performed. The currently reported uncertainties are still in the order of 50% [2, 3]. Neutron capture cross section measurements on a 4% enriched 85Kr gas enclosed in a stainless steel cylinder were performed at Los Alamos National Laboratory (LANL) using the Detector for Advanced Neutron Capture Experiments (DANCE). 85Kr is radioactive isotope with a half life of 10.8 years. As this was a low-enrichment sample, the main contaminants, the stable krypton isotopes 83Kr and 86Kr, were also investigated. The material was highly enriched and contained in pressurized stainless steel spheres.

  11. Neutron capture cross sections of Kr

    Directory of Open Access Journals (Sweden)

    Fiebiger Stefan

    2017-01-01

    Full Text Available Neutron capture and β− -decay are competing branches of the s-process nucleosynthesis path at 85Kr [1], which makes it an important branching point. The knowledge of its neutron capture cross section is therefore essential to constrain stellar models of nucleosynthesis. Despite its importance for different fields, no direct measurement of the cross section of 85Kr in the keV-regime has been performed. The currently reported uncertainties are still in the order of 50% [2, 3]. Neutron capture cross section measurements on a 4% enriched 85Kr gas enclosed in a stainless steel cylinder were performed at Los Alamos National Laboratory (LANL using the Detector for Advanced Neutron Capture Experiments (DANCE. 85Kr is radioactive isotope with a half life of 10.8 years. As this was a low-enrichment sample, the main contaminants, the stable krypton isotopes 83Kr and 86Kr, were also investigated. The material was highly enriched and contained in pressurized stainless steel spheres.

  12. Subcellular boron and fluorine distributions with SIMS ion microscopy in BNCT and cancer research

    Energy Technology Data Exchange (ETDEWEB)

    Subhash Chandra

    2008-05-30

    The development of a secondary ion mass spectrometry (SIMS) based technique of Ion Microscopy in boron neutron capture therapy (BNCT) was the main goal of this project, so that one can study the subcellular location of boron-10 atoms and their partitioning between the normal and cancerous tissue. This information is fundamental for the screening of boronated drugs appropriate for neutron capture therapy of cancer. Our studies at Cornell concentrated mainly on studies of glioblastoma multiforme (GBM). The early years of the grant were dedicated to the development of cryogenic methods and correlative microscopic approaches so that a reliable subcellular analysis of boron-10 atoms can be made with SIMS. In later years SIMS was applied to animal models and human tissues of GBM for studying the efficacy of potential boronated agents in BNCT. Under this grant the SIMS program at Cornell attained a new level of excellence and collaborative SIMS studies were published with leading BNCT researchers in the U.S.

  13. Design of hyper-thermal neutron irradiation fields for neutron capture therapy in KUR-heavy water neutron irradiation facility. Mounting of hyper-thermal neutron converter in therapeutic collimator

    International Nuclear Information System (INIS)

    Sakurai, Y.; Kobayashi, T.

    2001-01-01

    Neutron capture therapy (NCP) using thermal neutron needs to improve of depth dose distribution in a living body. Epi-thermal neutron following moderation of fast neutron is usually used for improving of the depth dose distribution. The moderation method of fast neutron, however, gets mixed some of high energy neutron which give some of serious effects to a living body, and involves the difficulty for collimation of thermal neutron to the diseased part. Hyper-thermal neutrons, which are in an energy range of 0.1-3 eV at high temperature side of thermal neutron, are under consideration for application to the NCP. The hyper-thermal neutrons can be produced by up-scattering of thermal neutron in a high temperature material. Fast neutron components in collimator for the NCP reduce on application of the up-scattering method. Graphite at high temperature (>1000k) is used as a hyper-thermal neutron converter. The hyper-thermal neutron converter is planted to mount on therapeutic collimator which is located at the nearest side of patient for the NCP. Total neutron flux, ratio of hyper-thermal neutron to total neutron, and ratio of gamma-ray dose to neutron flux are calculated as a function of thickness of the graphite converter using monte carlo code MCNP-V4B. (M. Suetake)

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

    Energy Technology Data Exchange (ETDEWEB)

    Couture, Aaron Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-31

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

  15. Measurements of neutron capture cross sections

    International Nuclear Information System (INIS)

    Nakajima, Yutaka

    1984-01-01

    A review of measurement techniques for the neutron capture cross sections is presented. Sell transmission method, activation method, and prompt gamma-ray detection method are described using examples of capture cross section measurements. The capture cross section of 238 U measured by three different prompt gamma-ray detection methods (large liquid scintillator, Moxon-Rae detector, and pulse height weighting method) are compared and their discrepancies are resolved. A method how to derive the covariance is described. (author)

  16. Qualitative dose response of the normal canine head to epithermal neutron irradiation with and without boron capture

    International Nuclear Information System (INIS)

    DeHaan, C.E.; Gavin, P.R.; Kraft, S.L.; Wheeler, F.J.; Atkinson, C.A.

    1992-01-01

    Boron Neutron Capture Therapy is being re-evaluated for the treatment of intracranial tumors. Prior to human clinical trials, determination of normal tissue tolerance is critical. Dogs were chosen as a large animal model for the following reasons. Dogs can be evaluated with advanced imaging, diagnostic and therapeutic modalities. Dogs are amenable to detailed neurologic examination and subtle behavioral changes are easily detected. Specifically, Labrador retrievers were chosen for their large body and head size. The dogs received varying doses of epithermal neutron irradiation and boron neutron capture irradiation using an epithermal neutron source. The dogs were closely monitored for up to one year post irradiation

  17. Neutron capture cross section of $^{93}$Zr

    CERN Multimedia

    We propose to measure the neutron capture cross section of the radioactive isotope $^{93}$Zr. This project aims at the substantial improvement of existing results for applications in nuclear astrophysics and emerging nuclear technologies. In particular, the superior quality of the data that can be obtained at n_TOF will allow on one side a better characterization of s-process nucleosynthesis and on the other side a more accurate material balance in systems for transmutation of nuclear waste, given that this radioactive isotope is widely present in fission products.

  18. Measurement of thermal neutron capture cross section

    International Nuclear Information System (INIS)

    Huang Xiaolong; Han Xiaogang; Yu Weixiang; Lu Hanlin; Zhao Wenrong

    2001-01-01

    The thermal neutron capture cross sections of 71 Ga(n, γ) 72 Ga, 94 Zr(n, γ) 95 Zr and 191 Ir(n, γ) 192 Ir m1+g,m2 reactions were measured by using activation method and compared with other measured data. Meanwhile the half-life of 72 Ga was also measured. The samples were irradiated with the neutron in the thermal column of heavy water reactor of China Institute of Atomic Energy. The activities of the reaction products were measured by well-calibrated Ge(Li) detector

  19. Neutron Capture Cross Section of 239Pu

    Science.gov (United States)

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

    2014-09-01

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

  20. High lateral resolution, quantitative SIMS analysis of boron-10 in rat brain tissue

    International Nuclear Information System (INIS)

    Oyedepo, A.C.; Heard, P.J.; Allen, G.C.; Brooke, S.L.; Patel, H.

    2000-01-01

    A SIMS (Secondary Ion Mass Spectroscopy) instrument providing high-resolution imaging has been used to examine the relative amounts of boron-10 ( 10 B) taken up in tumour and normal areas of rat brain tissue. It was possible to identify regions of low and high 10 B concentrations. The information is useful to the advancement of BNCT (Boron Neutron Capture Therapy) clinical trials. (author)

  1. Determination of boron concentration in biopsy-sized tissue samples

    International Nuclear Information System (INIS)

    Hou, Yougjin; Fong, Katrina; Edwards, Benjamin; Autry-Conwell, Susan; Boggan, James

    2000-01-01

    Inductively coupled plasma mass spectrometry (ICP-MS) is the most sensitive analytical method for boron determination. However, because boron is volatile and ubiquitous in nature, low-concentration boron sample measurement remains a challenge. In this study, an improved ICP-MS method was developed for quantitation of tissue samples with low (less than 10 ppb) and high (100 ppb) boron concentrations. The addition of an ammonia-mannitol solution converts volatile boric acid to the non-volatile ammonium borate in the spray chamber and with the formation of a boron-mannitol complex, the boron memory effect and background are greatly reduced. This results in measurements that are more accurate, repeatable, and efficient. This improved analysis method has facilitated rapid and reliable tissue biodistribution analyses of newly developed boronated compounds for potential use in neutron capture therapy. (author)

  2. Use of ABAREX for neutron capture calculations

    International Nuclear Information System (INIS)

    Moldauer, P.A.

    1982-01-01

    ABAREX is an optical-statistical model program for the calculation of energy averaged neutron induced nuclear reaction cross sections. The program uses the optical model algorithm of ABACUS and the statistical model method of NEARREX with many improvements and modifications. The input and output are designed to be convenient for the user and the program utilizes dynamic storage allocation with avoids fixed limits on the sizes of the various arrays. The program requires 250K storage in the IBM 370 system in its present configuration. Additional storage can easily be made available. For optical model parameter fitting, the program uses the subroutine LMDIF1 of the MINPACK-1 package of subroutines for the solution of nonlinear least square problems. No detailed description of the program will be attempted here. The capabilities and uses of the program will be outlined with special reference to neutron capture cross sections

  3. Thermal neutron capture gamma-rays

    International Nuclear Information System (INIS)

    Tuli, J.K.

    1983-01-01

    The energy and intensity of gamma rays as seen in thermal neutron capture are presented. Only those (n,α), E = thermal, reactions for which the residual nucleus mass number is greater than or equal to 45 are included. These correspond to evaluations published in Nuclear Data Sheets. The publication source data are contained in the Evaluated Nuclear Structure Data File (ENSDF). The data presented here do not involve any additional evaluation. Appendix I lists all the residual nuclides for which the data are included here. Appendix II gives a cumulated index to A-chain evaluations including the year of publication. The capture gamma ray data are given in two tables - the Table 1 is the list of all gamma rays seen in (n,#betta#) reaction given in the order of increasing energy; the Table II lists the gamma rays according to the nuclide

  4. Boron isotopic enrichment by displacement chromatography

    International Nuclear Information System (INIS)

    Mohapatra, K.K.; Bose, Arun

    2014-01-01

    10 B enriched boron is used in applications requiring high volumetric neutron absorption (absorption cross section- 3837 barn for thermal and 1 barn for 1 MeV fast neutron). It is used in fast breeder reactor (as control rod material), in neutron counter, in Boron Neutron Capture Therapy etc. Owing to very small separation factor, boron isotopic enrichment is a complex process requiring large number of separation stages. Heavy Water Board has ventured in industrial scale production of 10 B enriched boron using Exchange Distillation Process as well as Ion Displacement Chromatography Process. Ion Displacement Chromatography process is used in Boron Enrichment Plant at HWP, Manuguru. It is based on isotopic exchange between borate ions (B(OH) 4 - ) on anion exchange resin and boric acid passing through resin. The isotopic exchange takes place due to difference in zero point energy of 10 B and 11 B

  5. Selected topics in thermal and resonance neutron capture

    International Nuclear Information System (INIS)

    Raman, S.

    1981-01-01

    Several topics of current interest are discussed including energy and intensity standards, direct thermal neutron capture, primary E2 transitions in (n,γ) reactions, nonstatistical effects in resonance neutron capture, transmission measurements of Sc employed in 2-keV facilities, and tests of Axel-Brink predictions of γ-ray strength functions via average resonance capture

  6. Inhibition of growth of human breast cancer cells in culture by neutron capture using liposomes containing 10B.

    Science.gov (United States)

    Yanagië, H; Kobayashi, H; Take