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Sample records for boron neutron-capture therapy

  1. Boron neutron capture therapy. What is next?

    International Nuclear Information System (INIS)

    BNCT (Boron Neutron Capture Therapy) will have difficulties establishing itself without efficient and conclusive clinical trials of glioma, without the expansion to other tumors, and without efficient programs for compound development and testing. (author)

  2. Clinical aspects of boron neutron capture therapy

    International Nuclear Information System (INIS)

    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. Microdosimetry for Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    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

  4. Considerations on boron neutron capture therapy

    International Nuclear Information System (INIS)

    This article reviews the radiotherapy technique called Boron Neutron Capture Therapy - BNCT. Herein, basic concepts in BNCT are addressed, particularly how BNCT has been used in the attempts of defeating multiform glioblastoma. The history of the BNCT trials in the 50's and 60's, including the previous trials at Brookhaven National Laboratory (BNL) and at the Massachusetts Institute of Technology (MIT) are presented. The Japanese experience in BNCT is discussed. Recently, clinical trials at the MIT and BNL have started, focusing multiform glioblastoma and peripheral and intracranial melanomas. Radiobiological and clinical data from Phase I trials on MIT are discussed. Considerations in how BNCT can be developed in Brazil are presented. It shows that Cf-252 Brachytherapy coupled with NCT may be a non-expensive, alternative way of addressing BNCT. (author)

  5. Considerations for boron neutron capture therapy studies

    International Nuclear Information System (INIS)

    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

  6. Anesthetic management of Boron Neutron Capture Therapy for glioblastoma

    International Nuclear Information System (INIS)

    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)

  7. Approach to boron neutron capture therapy in Europe: goals of a European Collaboration on Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    A European Collaboration on Boron Neutron Capture Therapy has been founded in 1989. This Collaboration wants to create all necessary conditions to establish neutron capture therapy as a clinical therapy in Europe. For this, two main goals are being pursued: to initiate, at the High Flux Reactor in Petten (The Netherlands) clinical trials of glioma and melanoma and to create conditions that other tumors can be treated at this and other sites. The approach towards clinical trials of gliomas with boron neutron capture therapy is detailed. The necessary development of an epithermal neutron beam, and the necessary healthy tissue tolerance studies are discussed in view of the particularities of the radiobiology of boron neutron capture therapy. (author) 5 refs.; 2 figs

  8. Proceedings of workshop on 'boron chemistry for neutron capture therapy'

    International Nuclear Information System (INIS)

    This volume contains the proceedings of the workshop on the chemistry of Boron Neutron Capture Therapy held on 1st of August in 1988 and on 22nd of January in 1990. In this workshop, our attention was mainly focused on the chemical reactions and chemical analyses of boron compounds used for the therapy. There is additionally shown the basic knowledge of immunology related with the neutron capture therapy. We do hope that this proceedings will contribute to the development of new boron carriers for the therapy. (J.P.N.)

  9. Role of gel dosimeters in boron neutron capture therapy

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

    2015-09-01

    Boron neutron capture therapy (BNCT) is a promising cancer therapy modality that utilizes the nuclear capture reaction of epithermal neutrons by boron-10 resulting in a localized nuclear fission reaction and subsequent cell death. Since cellular destruction is limited to approximately the diameter of a single cell, primarily only cells in the neutron field with significant boron accumulation will be damaged. However, the emergence of BNCT as a prominent therapy has in large part been hindered by a paucity of tumor selective boron containing agents. While L-boronophenylalanine and sodium borocaptate are the most commonly investigated clinical agents, new agents are desperately needed due to their suboptimal tumor selectivity. This review will highlight the various strategies to improve tumor boron delivery including: nucleoside and carbohydrate analogs, unnatural amino acids, porphyrins, antibody-dendrimer conjugates, cationic polymers, cell-membrane penetrating peptides, liposomes and nanoparticles. PMID:26033767

  11. Medical and biological requirements for boron neutron capture therapy

    International Nuclear Information System (INIS)

    In conventional radiation therapy, tumor doses applied to most solid tumors are limited by the tolerance of normal tissues. The promise of Boron Neutron Capture Therapy lies in its potential to deposit high doses of radiation very specifically to tumor tissue. Theoretically ratios of tumor to normal tissue doses can be achieved significantly higher than conventional radiotherapeutic techniques would allow. Effective dose distributions obtainable are a complex function of the neutron beam characteristics and the macro and micro distributions of boron in tumor and normal tissues. Effective RBE doses are calculated in tumors and normal tissue for thermal, epithermal and 2 keV neutrons

  12. Some progress in boron neutron capture therapy

    International Nuclear Information System (INIS)

    After a historical overview of the application of neutrons to cancer therapy, collaboration is suggested for the application of BNCT with relativistic nuclei in the fields of neutron sources, microdosimetry and tumor selection. The treatment of uveal melanoma is considered. (R.P.) 4 refs.; 1 fig

  13. Design study of facilities for boron neutron capture therapy

    International Nuclear Information System (INIS)

    One of the authors organized a research group on boron neutron capture therapy (BNCT) during 1975 to 1979. The results of the research were summarized in two Japanese reports. It was concluded in 1976 that a nuclear reactor facility was required for developing BNCT and related research. Conceptual design of the facility was performed according to consultation among the group members, and is reported here. The optimum neutron energy for BNCT is shown to be between 10eV and 500eV

  14. Experience of boron neutron capture therapy in Japan

    International Nuclear Information System (INIS)

    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. Goals of the European Collaboration on boron neutron capture therapy

    International Nuclear Information System (INIS)

    Since 1989, the Commission of the European Community (CEC) funds, through their program Europe against Cancer, a Concerted Action European Collaboration on Boron Neutron Capture Therapy. The European Collaboration has two main goals. Goal 1 is to initiate clinical trials of glioma at the High Flux Reactor Petten at the earliest possible time. Goal 2 is to create all necessary conditions to initiate clinical trials of other tumors and treatment at other facilities. In this overview the activities of European Collaboration towards the two goals are summarized

  16. Slow neutron capture therapy for malignant glioma (boron or lithium neutron capture therapy)

    International Nuclear Information System (INIS)

    In recurrent glioblastoma, the mean survival period is approx. 6 months by the routine methods of treatment, but is extended more than 3-fold by neutron capture therapy. This method and a routine method with 60Co or an accelerator were used for comparison in the clinical treatment of 26 patients with supratentorial malignant glioma. There were no significant differences as for prognostic factors of the group treated by this method and those of the control group; No. of cases 14 and 12, the mean age 46 and 53.5 yr, and the stage (TNM) 3.14 and 2.83, respectively. As of the end of Feb. 1980, this method showed a lifeprolonging effect 3 times that of the control, the mean survival period being 67 weeks for this method and 21 for the control. Although 100% improvement was observed in about one half of the cases by this method, the control group showed improvement of only 80% at maximum. It is also possible to treat any deep portion of the brain with thermal neutrons. As a Boron compound, mercaptoundecahydrododecarborate with a low toxicity has been put into practical use for brain tumors, and as Li, the use of 6LiCl for lung cancer is under examination. (Chiba, N.)

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

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is a promising technique for the treatment of selected types of brain tumor and potentially for other tumor types. In this therapy, a 10B-enriched species is administered to the bloodstream and selectively deposited in the tumor. The selective deposition in the tumor is due to either the breakdown of the blood-grain barrier or to the chemical nature of the boron-containing compounds. Once a sufficient concentration of boron is attained in the tumor (approximately 25 ppm), the tumor is irradiated with a controlled energy neutron beam (preferable epithermal, 1 eV to 10 keV), at which time neutrons are captured by the incorporated boron atoms. The capture results in the reaction, 10B(n, ) Li, which produces a localized nuclear reaction capable of destroying the tumor cell containing the boron. A variety of boron containing compounds have been evaluated for use in BNCT. This paper addresses some of the most promising of the compounds, the disodium salt of mercaptoundecahydrododecaborate (Na2B12H11SH), commonly referred to as BSH

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

    International Nuclear Information System (INIS)

    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)

  19. Recombination methods for boron neutron capture therapy dosimetry

    International Nuclear Information System (INIS)

    The radiation effects of boron neutron capture therapy (BNCT) are associated with four-dose-compartment radiation field - boron dose (from 10B(n,α)7Li) reaction), proton dose from 14N(n,p)14C reaction, neutron dose (mainly fast and epithermal neutrons) and gamma-ray dose (external and from capture reaction 1H(n,γ)2D). Because of this the relation between the absorbed dose and the biological effects is very complex and all the above mentioned absorbed dose components should be determined. From this point of view, the recombination chambers can be very useful instruments for characterization of the BNCT beams. They can be used for determination of gamma and high-LET dose components for the characterization of radiation quality of mixed radiation fields by recombination microdosimetric method (RMM). In present work, a graphite high-pressure recombination chamber filled with nitrogen, 10BF3 and tissue equivalent gas was used for studies on application of RMM for BNCT dosimetry. The use of these gases or their mixtures opens a possibility to design a recombination chamber for determination of the dose fractions due to gamma radiation, fast neutrons, neutron capture on nitrogen and high LET particles from (n,10B) reaction in simulated tissue with different content of 10B. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-04-01

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

  1. Boron Neutron Capture Therapy for Malignant Brain Tumors

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

    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., 109 n/cm2/sec) may be measured because of this potentially high count rate and the small diameter of the fiber

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

    International Nuclear Information System (INIS)

    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.)

  4. 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.)

  5. Towards epithermal boron neutron capture therapy for cancer

    International Nuclear Information System (INIS)

    Progress in the treatment of local disseminating cancer such as high grade brain tumours is poor, and the ability to kill individual cancer cells in the midst of normal cells has not been achieved. Binary therapies hold the most promise of this, and of these Boron Neutron Capture Therapy (BNCT) is the most advanced. Epithermal neutron beams are essential for outpatient treatment of high grade brain tumours and these are now installed and being characterised in Europe and the USA, and are at the design stage in Australia. These beams would allow the bilateral irradiation of the entire brain, and as such are ideally suited for the prophylactic therapy of subclinical metastases. When coupled with appropriate cancer affined boron compounds, therapeutic ratios of 2-3 should be achieved. At present the only source of an epithermal neutron beam is a nuclear reactor. The Euratom reactor at Petten and the Brookhaven Medical Reactor have been retrofitted with filters to produced an epithermal neutron beam. These beams have been characterised and used in dose escalation studies with dogs to study normal tissue tolerance using borocaptate (BSH). Another beam is available at the MIT medical research reactor. Clinical trails at Petten for glioblastoma with BSH and at MIT using boronophenylalanine for melanoma metastases to the extremities are expected to commence this year. The state of the art of reactor based BNCT is reviewed and the potential for a major change in the prognosis of local control of disseminating cancer is explored. 29 refs.,

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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 Na210B12H11SH 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)

  8. Quality Assurance of Patient Dosimetry in Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    The verification of the correctness of planned and executed treatments is imperative for safety in radiotherapy. The purpose of the present work is to describe and evaluate the quality assurance (QA) procedures for patient dosimetry implemented at the boron neutron capture therapy (BNCT) facility at Studsvik, Sweden. The dosimetric complexity of the mixed neutron-photon field during BNCT suggests a careful verification of routine procedures, specifically the treatment planning calculations. In the present study, two methods for QA of patient dosimetry are presented. The first is executed prior to radiotherapy and involves an independent check of the planned absorbed dose to be delivered to a point in the patient for each treatment field. The second QA procedure involves in vivo dosimetry measurements using post-treatment activation analysis. Absorbed dose conversion factors taking the difference in material composition and geometry of the patient and the PMMA phantom used for reference dosimetry were determined using the Monte Carlo method. The agreement of the QA procedure prior to radiotherapy reveals an acceptably small deviation for 60 treatment fields of ±4.2% (1 SD), while the in vivo dosimetry method presented may benefit from improvements, as the deviations observed were quite substantial (±12%, 1 SD), and were unlikely to be due to actual errors in the clinical dosimetry

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

    International Nuclear Information System (INIS)

    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.

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

    International Nuclear Information System (INIS)

    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. Boron neutron capture therapy for recurrent head and neck malignancies

    International Nuclear Information System (INIS)

    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) 10B 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)

  12. The Finnish Boron neutron capture therapy (BNCT) project

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is a new, binary radiotherapy, which has been developed especially for severe brain tumours, incurable by the present means. A suitable 10B containing carrier compound is injected into the blood circulation and taken up selectively by the cancer cells. When these cells are subjected to a thermal neutron field, the 10B atoms capture the neutrons and undergo fission reaction. The energy thereby released is killing the cancerous cell. The Finnish BNCT research and development project is in the situation where all the basic conditions exist to start clinical trials. An epithermal neutron irradiation facility has been constructed at the Finnish research reactor (FiR 1) operated by VTT in Otaniemi. This article is an overview over the developments within the Finnish BNCT project. A research project to carry out clinical application of BNCT was established in Finland in the early 1990's. It was motivated both by the need to create new uses for FiR 1 and by the ideas to start research and production of new boron carriers for BNCT in Finland. Soon also other medical, medical physics and chemistry disciplines joined the project. Now the project involves scientists from different departments of University of Helsinki (HU), Helsinki University Central Hospital (HUCH), Technical Research Centre of Finland (VTT), Finnish Radiation and Nuclear Safety Authority (STUK) and of the Helsinki University of Technology (HUT) and other Finnish universities. The aim of this project has been to start BNC-treatment of malignant brain tumours in Finland by the end of the century

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

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is a tumor-cell targeted radiotherapy. When 10B absorbs thermal neutrons, the alpha and 7Li particles generated by the 10B (n, α) 7Li 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 10B. 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. Physical engineering for boron neutron capture therapy in KUR

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Toru [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst

    2001-01-01

    Basic results of physical engineering study for neutron capture therapy in KUR have been reported since 1970, such as (1) development of thermal neutron fields for therapy following with low {gamma}-ray, (2) development of thermal neutron shield material ({sup 6}LiF) following with low secondary {gamma}-ray, (3) establishment of measurement techniques for B-10 concentration in tissue by using then (n,{gamma}) reaction, (4) evaluation of absorbed dose in a cell level during neutron capture therapy. It is difficult for many of thermal neutrons to reach to the depths in tissue. The thermal neutron irradiation, therefore, is suitable for the therapy of cancer on surface tissue, but not suitable for the therapy of cancer in the depths. Uses of epi-thermal (0.5 eV - 10 keV) or hyper-thermal (>0.5 eV) neutrons, instead of thermal neutron are considered for the neutron capture therapy to cancer in the depth. The depth dose distributions of thermal neutron are improved by increase of forward component of the epi-thermal or the hyper-thermal neutron. Thermal neutron fluxes have been measured by the activation method of Au-197. Thermo-luminescent detector (MgSiO4, or BeO) is used for the measurement of {gamma}-ray doses. Noninvasive dose estimation at cancer parts is developed with a prompt {gamma}-ray analysis method using HPGe and CdTe semiconductor detectors. (Suetake, M.)

  15. Beryllium Target for Accelerator - Based Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    This work is part of a project for developing Accelerator Based Boron Neutron Capture Therapy (AB- BNCT) for which the generation of neutrons through nuclear reactions like 9Be(d,n) is necessary. In this paper first results of the design and development of such neutron production targets are presented. For this purpose, the neutron production target has to be able to withstand the mechanical and thermal stresses produced by intense beams of deuterons (of 1.4 MeV with a total current of about 30mA). In particular, the target should be able to dissipate an energy density of up to 1 kW/cm2 and preserve its physical and mechanical properties for a sufficient length of time under irradiation conditions and hydrogen damage. The target is proposed to consist of a thin Be deposit (neutron producing material) on a thin W or Mo layer to stop the beam and a Cu backing to help carry away the heat load. To achieve the adhesion of the Be films on W, Mo and Cu substrates, a powder blasting technique was applied with quartz and alumina microspheres. On the other hand, Ag deposits were made on some of the substrates previously blasted to favor the chemical affinity between Beryllium and the substrate thus improving adhesion. Be deposits were characterized by means of different techniques including Electron Microscopy (Sem) and Xr Diffraction. Roughness and thickness measurements were also made. To satisfy the power dissipation requirements for the neutron production target, a microchannel system model is proposed. The simulation based on this model permits to determine the geometric parameters of the prototype complying with the requirements of a microchannel system. Results were compared with those in several publications and discrepancies lower than 10% were found in all cases. A prototype for model validation is designed here for which simulations of fluid and structural mechanics were carried out and discussed

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-05-01

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

  18. A suggestion for B-10 imaging during boron neutron capture therapy

    OpenAIRE

    Cortesi, M.

    2007-01-01

    Selective accumulation of B-10 compound in tumour tissue is a fundamental condition for the achievement of BNCT (Boron Neutron Capture Therapy), since the effectiveness of therapy irradiation derives just from neutron capture reaction of B-10. Hence, the determination of the B-10 concentration ratio, between tumour and healthy tissue, and a control of this ratio, during the therapy, are essential to optimise the effectiveness of the BNCT, which it is known to be based on the selective uptake ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Ackermann, A.L. (ed.); Dorn, R.V. III.

    1990-08-01

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

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

    Science.gov (United States)

    Liu, Hungyuan B.

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

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

    International Nuclear Information System (INIS)

    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)

  2. Inefficiency of high boron concentrations for cell killing in boron neutron capture therapy

    International Nuclear Information System (INIS)

    This study is to investigate the relationship between the cell-killing effect of the 10B(n, α)7Li capture reaction, intracellular boron concentration, and thermal neutron fluence in boron neutron capture therapy using in vitro cell survival based on a clonogenic assay, and biophysical analysis. Our results showed that the cell-killing yield of the 10B(n, α)7Li capture reaction per unit thermal neutron fluence declined with an increase in the intracellular boron concentration above 45 μg/ml 10B. The cell-killing effect was well described using an empirical power function of the intracellular boron concentration, with exponent 0.443. Knowledge of this effect will help in the optimization of BNCT. (author)

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

    International Nuclear Information System (INIS)

    We used synchrotron spectromicroscopy to study the microscopic distribution of boron in rat brain tumour and healthy tissue in the field of boron neutron capture therapy (BNCT). The success of this experimental cancer therapy depends on the preferential uptake of 10B in tumour cells after injection of a boron compound (in our case B12H11SH, or BSH). With the Mephisto (microscope a emission de photoelectrons par illumination synchrotronique de type onduleur) spectromicroscope, high-magnification imaging and chemical analysis was performed on brain tissue sections from a rat carrying an implanted brain tumour and the results were compared with inductively coupled plasma-atomic emission spectroscopy (ICP-AES) detection of boron in bulk tissue. Boron was found to have been taken up more favourably by regions of tumour rather than healthy tissue, but the resulting boron distribution in the tumour was inhomogeneous. The results demonstrate that Mephisto can perform microchemical analysis of tissue sections, detect and localize the presence of boron with submicron spatial resolution. The application of this technique to boron in brain tissue can therefore be used to evaluate the current efforts to optimize BNC therapy. (author)

  4. A novel method of boron delivery using sodium iodide symporter for boron neutron capture therapy

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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.)

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

    International Nuclear Information System (INIS)

    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.)

  7. Synthesis and evaluation of boron folates for Boron-Neutron-Capture-Therapy (BNCT)

    Energy Technology Data Exchange (ETDEWEB)

    Kettenbach, Kathrin; Schieferstein, Hanno; Grunewald, Catrin; Hampel, Gabriele; Schuetz, Christian L. [Mainz Univ. (Germany). Inst. of Nuclear Chemistry; Iffland, Dorothee; Bings, Nicolas H. [Mainz Univ. (Germany). Inst. of Inorganic Chemistry and Analytical Chemistry; Reffert, Laura M. [Hannover Medical School (Germany). Radiopharmaceutical Chemistry; Ross, Tobias L. [Mainz Univ. (Germany). Inst. of Nuclear Chemistry; Hannover Medical School (Germany). Radiopharmaceutical Chemistry

    2015-07-01

    Boron neutron capture therapy (BNCT) employs {sup 10}B-pharmaceuticals administered for the treatment of malignancies, and subsequently irradiated with thermal neutrons. So far, clinical established pharmaceuticals like boron phenylalanine (BPA) or sodium boron mercaptate (BSH) use imperfect (BPA) or passive (BSH) targeting for accumulation at target sites. Due to the need of a selective transportation of boron drugs into cancer cells and sparing healthy tissues, we combined the BNCT approach with the specific and effective folate receptor (FR) targeting concept. The FR is overexpressed on many human carcinomas and provides a selective and specific target for molecular imaging as well as for tumor therapy. We synthesized and characterized a carborane-folate as well as a BSH-folate to study their in vitro characteristics and their potential as new boron-carriers for BNCT. Uptake studies were carried out using human KB cells showing a significant increase of the boron content in cells and demonstrating the successful combination of active FR-targeting and BNCT.

  8. Commercial Clinical Application of Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    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 (Na2B10H10) as the first boron agent of interest. An Investigational New Drug (IND) application for GB-10 has been filed and approved by the FDA for a Phase I human biodistribution trial in patients with non-small cell lung cancer and glioblastoma multiforme at UW under the direction of Professor Keith Stelzer, Principal Investigator (PI). These trials are funded by NTL under a contract with the UW, Department of Radiation Oncology, and the initial phases are nearing completion. Initial results show that boron-10 concentrations on the order of 100 micrograms per gram (100 ppm) can be achieved and maintained in blood with no indication of toxicity

  9. Commercial Clinical Application of Boron Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    N/A

    1999-09-03

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

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    Osteosarcoma is a malignant tumor commonly found in human and animals. The ability of boric acid (BA) to accumulate in osteosarcoma due to the mechanism of the bone formation of cancer cells would make boron neutron capture therapy (BNCT) an alternative therapy for osteosarcoma. This study evaluated the feasibility of using BA as the boron drug for BNCT of bone cancer. The cytotoxicity of BA to L929 cells exceeded that of UMR-106 cells. With 25 μg 10B/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 10B/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.

  12. The three dimensional map of dose components in a head phantom for boron neutron capture therapy

    Directory of Open Access Journals (Sweden)

    Bavarnegin Elham

    2013-01-01

    Full Text Available The in-phantom measurement of physical dose distribution and construction of a convenient phantom is very important for boron neutron capture therapy planning validation. In this study we have simulated a head phantom, suggested for construction in boron neutron capture therapy facilities, and calculated all relevant dose components inside of it using the Monte Carlo code MCNPX. A “generic” epithermal neutron beam with a broad neutron spectrum, similar to beams used for neutron capture therapy clinical trials, was used. The calculated distributions of all relevant dose components in brain tissue equivalent were compared with those in water. The results show that water is a suitable dosimetry material and that the simulated head phantom is a suitable design for producing accurate three-dimensional maps of dose components at enough points inside of the phantom for boron neutron capture therapy dosimetry measurements and the use of these dose maps in beam development and benchmarking of computer-based treatment codes.

  13. Formulation and preliminary evaluation of delivery vehicles for the boron neutron capture therapy of cancer

    OpenAIRE

    Olusanya, Temidayo; Stich, Theresia; Higgins, Samantha Caroline; Lloyd, Rhiannon Eleanor Iris; Smith, James Richard; Fatouros, Dimitrios; Calabrese, Gianpiero; Pilkington, Geoffrey John; Tsibouklis, John

    2015-01-01

    Boron neutron capture therapy (BNCT) is a method for selectively destroying malignant (normally glioma) cells whilst sparing normal tissue1. Irradiation of 10B (large neutron capture cross-section) with thermal neutrons effects the nuclear fission reaction: 10B + 1n → → 7Li+ + α + γ; where the penetration of α-particles and 7Li+ is only 8 and 5 µm, respectively, i.e., within a single cell thickness, assuming 10B can be preferentially located within glioma cells2. Poor selectivity is the main ...

  14. Formulation and preliminary evaluation of delivery vehicles for the boron neutron capture therapy of cancer

    OpenAIRE

    Olusanya, Temidayo Olajumoke Bolanle

    2015-01-01

    Boron neutron capture therapy (BNCT) is a method for selectively destroying malignant (normally glioma) cells whilst sparing normal tissue. Irradiation of 10B (large neutron capture cross-section) with thermal neutrons effects the nuclear fission reaction: 10B + 1n → → 7Li+ + α + γ; where the penetration of -particles and 7Li+ is only 8 and 5 μm, respectively, i.e., within a single cell thickness, assuming 10B can be preferentially located within glioma cells. Poor selectivity is the main r...

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

    International Nuclear Information System (INIS)

    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 (1H-NMR, 13C-NMR) and matrix assisted laser desorption/ionization techniques. The synthesized dendrimer presented low dispersion in molecular weights (Mw/Mn = 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 10B-PGLD dendrimer indicate lower cytotoxicity, suggesting that the macromolecule is a biocompatible material. (author)

  16. Antitumor potential induction and free radicals production in melanoma cells by Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Antiproliferative and oxidative damage effects occurring in Boron Neutron Capture Therapy (BNCT) in normal fibroblasts and melanoma cell lines were analyzed. Melanoma cells and normal fibroblasts were treated with different concentrations of Boronophenylalanine and irradiated with thermal neutron flux. The cellular viability and the oxidative stress were determined. BNCT induced free radicals production and proliferative potential inhibition in melanoma cells. Therefore, this therapeutic technique could be considered efficient to inhibit growth of melanoma with minimal effects on normal tissues. - Highlights: ► Boron Neutron Capture Therapy (BNCT) induces melanoma cell death. ► BNCT stimulates free radicals production and proliferative inhibition in melanoma cells. ► It produces tumor membrane degeneration and destruction with apoptotic bodies formation. ► This therapy damages tumor cells selectively, with minimum effects on normal adjacent tissue.

  17. Antitumor potential induction and free radicals production in melanoma cells by Boron Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Faiao-Flores, F. [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)] [Faculty of Medicine, University of Sao Paulo, 455 Doutor Arnaldo Avenue, Sao Paulo (Brazil); Coelho, P.R.P.; Muniz, R.O.R.; Souza, G.S. [Institute for Nuclear and Energy Research, 2242 Lineu Prestes Avenue, Sao Paulo (Brazil); Arruda-Neto, J. [Physics Institute, University of Sao Paulo, 187 Matao Street, Sao Paulo (Brazil)] [FESP, Sao Paulo Engineering School, 5520 Nove de Julho Avenue, Sao Paulo (Brazil); Maria, Durvanei A., E-mail: durvaneiaugusto@yahoo.com.br [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)

    2011-12-15

    Antiproliferative and oxidative damage effects occurring in Boron Neutron Capture Therapy (BNCT) in normal fibroblasts and melanoma cell lines were analyzed. Melanoma cells and normal fibroblasts were treated with different concentrations of Boronophenylalanine and irradiated with thermal neutron flux. The cellular viability and the oxidative stress were determined. BNCT induced free radicals production and proliferative potential inhibition in melanoma cells. Therefore, this therapeutic technique could be considered efficient to inhibit growth of melanoma with minimal effects on normal tissues. - Highlights: Black-Right-Pointing-Pointer Boron Neutron Capture Therapy (BNCT) induces melanoma cell death. Black-Right-Pointing-Pointer BNCT stimulates free radicals production and proliferative inhibition in melanoma cells. Black-Right-Pointing-Pointer It produces tumor membrane degeneration and destruction with apoptotic bodies formation. Black-Right-Pointing-Pointer This therapy damages tumor cells selectively, with minimum effects on normal adjacent tissue.

  18. Tumor growth suppression by boron neutron capture therapy using PEG-liposomal boron delivery in vivo

    International Nuclear Information System (INIS)

    The tumor cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10B and thermal neutrons. We prepare a polyethylene glycol (PEG) binding liposome (DPPC/cholesterol/DSPC-PEG2000) entrapped 10B compound for the delivery system. We evaluated the cytotoxic effects of intravenously injected 10B-PEG-liposome on human pancreatic carcinoma (AsPC-1) xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with 10B-bare liposome or 10B-PEG-liposome, AsPC-1 tumour growth was suppressed relative to controls. Injection of 10B-PEG-liposome caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggests that intravenous injection of 10B-PEG-liposome can increase the retention of 10B atoms by tumor cells, causing tumor growth suppression in vivo upon thermal neutron irradiation. (author)

  19. Boron-11 NMR spectroscopy of excised mouse tissues after infusion of boron compound used in neutron capture therapy

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is based on selective boron uptake by the tumor and in situ activation by neutron beam. The authors propose the use of B-11 MR spectroscopy to noninvasively study boron uptake in animal tumor models. Sodium mercaptoundeca-hydrododecaborate was infused into female BALB/cJ mice and liver, brain, spleen, kidney, and tumor tissues were excised for MR (27.4MHz) and total boron content measurements. Boron-11 was easily detectable in tumor, liver, spleen, and skin. The results gave a very good correlation (correlation coefficient of .997) between B-11 MR measurements and total boron content of excised mouse tissues

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

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

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

    International Nuclear Information System (INIS)

    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 18F-BPA·PET and discuss several advantages to the application of BNCT to head and neck malignancies. (author)

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

    International Nuclear Information System (INIS)

    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

  3. 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...

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

    International Nuclear Information System (INIS)

    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. 10B, to sensitize tumor cells to irradiation by low energy (thermal) neutrons. The interaction of the 10B with a thermal neutron (neutron capture) causes the 10B nucleus to split, releasing an alpha particle and a lithium nucleus. These products of the 10B(n, α)7Li 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 10B-loaded cells

  5. 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.

  6. Medical aspects of boron-slow neutron capture therapy

    International Nuclear Information System (INIS)

    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 Na2 B12 H11 SH, number2 has yet to be achieved, and number3 has been solved by the measurement of the 478-keV gamma ray when the 10B 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 Na2 B12 H11SH 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

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

    International Nuclear Information System (INIS)

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

  8. Gene transfer-applied cancer boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mishima, Yutaka [ed.] [Mishima Institute for Dermatological Research, Kobe (Japan)

    1999-02-01

    On the basis of research progress made in basic investigations to clinical treatment in melanoma BNCT, we have advanced the present project through the application of the latest in melanogenesis research as well as cancer gene therapy. The multiple findings obtained during the fiscal years of 1997 and 1998 and contained in this current volume. (J.P.N.)

  9. Gene transfer-applied cancer boron neutron capture therapy

    International Nuclear Information System (INIS)

    On the basis of research progress made in basic investigations to clinical treatment in melanoma BNCT, we have advanced the present project through the application of the latest in melanogenesis research as well as cancer gene therapy. The multiple findings obtained during the fiscal years of 1997 and 1998 and contained in this current volume. (J.P.N.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhonglu

    2006-08-01

    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 cm{sup 2} treatment beam. The calculated boron dose enhancement at 5.7-cm depth in a water-filled head phantom in the assembly with a 5x5 cm{sup 2} collimation was 21.9% per 100-ppm {sup 10}B 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 cm{sup 2} fast neutron treatment beam. To validate the design calculations, a simplified BNCEFNT assembly was built using four lead bricks to form a 5x5 cm{sup 2} collimator. Five 1.0-cm thick 20x20 cm{sup 2} 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 {sup 10}B) to measure dose due to boron neutron capture. The measured dose enhancement at 5.0-cm depth

  11. 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.

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

    International Nuclear Information System (INIS)

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

  13. Proton nuclear magnetic resonance measurement of p-boronophenylalanine (BPA): A therapeutic agent for boron neutron capture therapy

    OpenAIRE

    Zuo, C. S.; Prasad, P V; Busse, Paul; L. Tang; Zamenhof, R. G.

    1999-01-01

    Noninvasive in vivo quantitation of boron is necessary for obtaining pharmacokinetic data on candidate boronated delivery agents developed for boron neutron capture therapy (BNCT). Such data, in turn, would facilitate the optimization of the temporal sequence of boronated drug infusion and neutron irradiation. Current approaches to obtaining such pharmacokinetic data include: positron emission tomography employing F-18 labeled boronated delivery agents (e.g., p-boronophenylalanine), ex vivo n...

  14. Biological Tests for Boron Neutron Capture Therapy Research at the TRIGA Mark II Reactor in Pavia

    International Nuclear Information System (INIS)

    The thermal column of the TRIGA Mark II reactor of the Pavia University is used as an irradiation facility to perform biological tests and irradiations of living systems for Boron Neutron Capture Therapy (BNCT) research. The suitability of the facility has been ensured by studying the neutron flux and the photon background in the irradiation chamber inside the thermal column. This characterization has been realized both by flux and dose measurements as well as by Monte Carlo simulations. The routine irradiations concern in vitro cells cultures and different tumor animal models to test the efficacy of the BNCT treatment. Some results about these experiments will be described. (author)

  15. Biological Tests for Boron Neutron Capture Therapy Research at the TRIGA Mark II Reactor in Pavia

    Energy Technology Data Exchange (ETDEWEB)

    Protti, N.; Ballarini, F.; Bortolussi, S.; De Bari, A.; Stella, S.; Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Nuclear Physics National Institute (INFN), Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Bakeine, J.G.; Cansolino, L.; Clerici, A.M. [Laboratory of Experimental Surgery, Department of Surgery, University of Pavia, Pavia (Italy)

    2011-07-01

    The thermal column of the TRIGA Mark II reactor of the Pavia University is used as an irradiation facility to perform biological tests and irradiations of living systems for Boron Neutron Capture Therapy (BNCT) research. The suitability of the facility has been ensured by studying the neutron flux and the photon background in the irradiation chamber inside the thermal column. This characterization has been realized both by flux and dose measurements as well as by Monte Carlo simulations. The routine irradiations concern in vitro cells cultures and different tumor animal models to test the efficacy of the BNCT treatment. Some results about these experiments will be described. (author)

  16. Incorporation and characterization of boron neutron capture therapy agents into mesoporous silicon and silicon nanowires

    International Nuclear Information System (INIS)

    The tunable pore size, biodegradability, and surface chemistry of mesoporous silicon (BioSilicon trademark) are important to a broad spectrum of uses for drug delivery. For the case of Boron Neutron Capture Therapy (BNCT), encapsulation of a given boron-containing drug molecule within a porous BioSilicon trademark microparticle provides a vehicle for a brachytherapy method that avoids the necessity of drug modification. In this work, the loading and characterization of three clinically approved BNCT drugs into mesoporous Si is demonstrated. Because of difficulties associated with light element detection, a method based on a Beer's Law analysis of selected FTIR vibrational bands has been developed to estimate boron-containing drug loading in these materials. As a complementary nanostructural platform, a cathodic deposition process for the surface enriched growth of selected drugs onto the surface of silicon nanowires is also described. (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  17. Incorporation and characterization of boron neutron capture therapy agents into mesoporous silicon and silicon nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Ke; Coffer, Jeffery L. [Department of Chemistry, Texas Christian University, Fort Worth, TX 76129 (United States); Loni, Armando; Canham, Leigh T. [PSi Medica Ltd., Malvern, Worcestershire, WR14 3SZ (United Kingdom); Intrinsiq Materials Ltd., Malvern, Worcestershire, WR14 3SZ (United Kingdom)

    2009-06-15

    The tunable pore size, biodegradability, and surface chemistry of mesoporous silicon (BioSilicon trademark) are important to a broad spectrum of uses for drug delivery. For the case of Boron Neutron Capture Therapy (BNCT), encapsulation of a given boron-containing drug molecule within a porous BioSilicon trademark microparticle provides a vehicle for a brachytherapy method that avoids the necessity of drug modification. In this work, the loading and characterization of three clinically approved BNCT drugs into mesoporous Si is demonstrated. Because of difficulties associated with light element detection, a method based on a Beer's Law analysis of selected FTIR vibrational bands has been developed to estimate boron-containing drug loading in these materials. As a complementary nanostructural platform, a cathodic deposition process for the surface enriched growth of selected drugs onto the surface of silicon nanowires is also described. (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

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

    International Nuclear Information System (INIS)

    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)

  19. Development of boronated tumor-seeking materials for application in neutron capture therapy of cancer

    International Nuclear Information System (INIS)

    Full text: At the present time the main field of application of boron compounds in medicine is Boron Neutron Capture Therapy (BNCT) of cancer. In this presentation the main principles of BNCT and main types of polyhedral boron compounds used for BNCT will be shown. The successful treatment of tumors by BNCT requires selective delivery of the boron moiety into the tumor cells. One of ways to solve this problem is attachment of boron fragment to different tumor-specific targeting molecules. Literature and our recent results on the preparation of novel boronated amino acids, carboranecarboxylic acids, a design of different conjugates of polyhedral boron compounds with tumor-seeking molecules, like porphyrins, phthalocyanines, nucleosides, carbohydrates, and lipids will be presented. Conjugates of natural porphyrins and phthalocyanines with carborane, closo-dodecaborate and cobalt bis(dicarbollide) were synthesized. The combination of these two fragments in one molecule makes these compounds potentially useful for both fluorescence diagnostics (FD) and BNCT of tumours. Boronated nucleosides are considered to be potential BNCT candidates because they can accumulate in the tumor cells. Thus, we have succeeded in preparation of the very first conjugates of closo-dodecaborate anion with one canonic nucleoside (thymidine)

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

    International Nuclear Information System (INIS)

    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 10B-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-g1-2-AEPB-g2-PEG was synthesized. -2-AEPB compound were bound to poly(acrylic acid) polymer at different three mole ratio.Then, the selected Poli(Ac)-g1-2-AEPB polymer was

  1. Single photon emission tomography approach for online patient dose assessment in boron neutron capture therapy

    International Nuclear Information System (INIS)

    A tomographic imaging system for the measurement of the spatial distribution of the absorbed dose during a Boron Neutron Capture Therapy (BNCT) session is presented. The 10B(n,α)7Li boron neutron capture reaction produces a 478 keV gamma ray in 94% of the cases. Therefore its detection can serve as a basis for a non-invasive online absorbed dose determination since the dose absorbed by the tumor and healthy tissue strongly depends on the boron uptake and the neutron flux. For this purpose, a dedicated tomographic imaging system based on Single Photon Emission Computed Tomography is proposed. Monte Carlo numerical simulations are used for the system design aimed to have a spatial resolution of 1 cm. Prototypes based on CdZnTe semiconductor detectors and LaBr3(Ce) scintillators with optimized shielding were designed with Monte Carlo simulations. They were built and tested in reactor and accelerator based BNCT facilities. A projection of a phantom with two tumors with 400 ppm of 10B was successfully measured at the accelerator facility of the University of Birmingham. (author)

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

    International Nuclear Information System (INIS)

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

  3. Research related to boron neutron capture therapy at The Ohio State University

    International Nuclear Information System (INIS)

    Research in the area of boron neutron capture therapy (BNCT) at The Ohio State University is a highly multidisciplinary effort involving approximately twenty investigators in nine different departments. Major areas of interest include: (1) Boronation of monoclonal antibodies directed against tumor-associated antigens for the delivery of 10B; (2) Synthesis of 10B-containing derivatives of promazines and porphyrins that possess tumor-localizing properties; (3) Development of a rat model for the treatment of glioblastoma by BNCT; (4) Quantitation and microdistribution of 10B in tissues by means of a solid state nuclear track detector. The ultimate goal of this research is to carry out the extensive preclinical studies that are required to bring BNCT to the point of a clinical trial. 13 references

  4. 72 MeV proton cyclotron for boron neutron capture therapy in Slovakia

    International Nuclear Information System (INIS)

    A cyclotron complex named CYLAB is being built at the Slovak Institute of Metrology. The main equipment, a cyclotron producing 72 MeV protons and light and heavy ions up to 129Xe20+, will be manufactured by the Joint Institute for Nuclear Research in Dubna. Medicine, physics, and metrology will be the main CYLAB application fields. The 66 MeV p-Be reaction will be used for fast neutron therapy, the spallation reactions of 72 MeV p on a tungsten target will be used in neutron capture therapy, and 72 MeV, 100 nA protons will be used in eye therapy. The medical applications of CYLAB are described with emphasis on boron neutron capture therapy (BNCT) and the gantry built for it, based on the 72 MeV/50 μA proton cyclotron. Theoretical calculations showed that in comparison with the equipment with a conventional configuration of moderators, reflectors, filters and shielding, significant improvements in epithermal neutron production will emerge, leading to a higher RBE dose rate at a 7 cm depth of the brain. (P.A.)

  5. A suggestion for B-10 imaging during boron neutron capture therapy

    CERN Document Server

    Cortesi, M

    2007-01-01

    Selective accumulation of B-10 compound in tumour tissue is a fundamental condition for the achievement of BNCT (Boron Neutron Capture Therapy), since the effectiveness of therapy irradiation derives just from neutron capture reaction of B-10. Hence, the determination of the B-10 concentration ratio, between tumour and healthy tissue, and a control of this ratio, during the therapy, are essential to optimise the effectiveness of the BNCT, which it is known to be based on the selective uptake of B-10 compound. In this work, experimental methods are proposed and evaluated for the determination in vivo of B-10 compound in biological samples, in particular based on neutron radiography and gammaray spectroscopy by telescopic system. Measures and Monte Carlo calculations have been performed to investigate the possibility of executing imaging of the 10B distribution, both by radiography with thermal neutrons, using 6LiF/ZnS:Ag scintillator screen and a CCD camera, and by spectroscopy, based on the revelation of gamm...

  6. High-current electrostatic accelerator-tandem for neutron generation for boron-neutron capture therapy

    International Nuclear Information System (INIS)

    The proton beam tandem accelerator project on the energy of 2.5 MeV and direct current up to 40 mA for solving the problems of boron-neutron capture therapy (BNCT) and fast neutron therapy is presented. The sectional high-voltage rectifier of the electron accelerator of the series EhLV is chosen as a high-voltage source. The rectifier voltage should be stabilized with accuracy of 0.1%. The recharge target and cryogenic vacuum discharge system are disposed inside high-voltage electrode. The problems on developing the reliable source of negative hydrogen ions, capable of maintaining the direct current up to 40 mA, are discussed

  7. Study of characteristics for heavy water photoneutron source in boron neutron capture therapy

    CERN Document Server

    Salehi, Danial; Sardari, Dariush

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS. - Highlights: • BNCT with the use of L-BPA was applied for three human clear cell sarcoma (CCS) cell lines. • BNCT trial was performed on a newly established intramuscularly CCS-bearing animal model. • A significant decrease of the tumor-volume was seen by single BNCT with the use of L-BPA. • A multiple BNCT application would be required for controlling the growth of any residual tumors

  9. Boron neutron capture therapy for advanced and/or recurrent cancers in the oral cavity

    International Nuclear Information System (INIS)

    This preliminary study of 5 patients with advanced and/or recurrent cancer in the oral cavity was performed to evaluate the effectiveness of Boron Neutron Capture Therapy (BNCT). The patients received therapy with the 10B-carrier p-boronophenylalanine (BPA) with or without borocaptate sodium (BSH) and irradiation thereafter with epithermal neutrons. All underwent 18F-BPA PET studies before receiving BNCT to determine the accumulation ratios of BPA in tumor and normal tissues. The tumor mass was decreased in size and at minimum a transient partial response was achieved in all cases, though rapid tumor re-growth was observed in 2. Although tentative clinical responses and improvements in quality of life were recognized, obliteration of the tumor was not obtained in any of the cases. Additional studies are required to determine the utility and indication of BNCT for oral cancer. (author)

  10. Micro-dosimetric study for interpretation of outcomes from boron neutron capture therapy clinical trials

    International Nuclear Information System (INIS)

    Boron neutron capture therapy is a brachy-radiotherapy utilizing the 10B(n,α)7Li reaction that has been used to treat glioblastoma multiforme (GBM), melanoma and colon carcinoma liver metastases. GBM clinical trials resulted in modestly improved life expectancies compared with conventional therapies. Early results trials focused on malignant melanoma and colon carcinoma provide dramatically better results. Macro-dosimetry cannot explain these apparent differences. The dichotomy can only be understood using Micro-dosimetry techniques. A computer program has been created to provide an improved tissue model. This model permits the dose in each cell's cytoplasm, nucleus, and the interstitium to be calculated for ellipsoidal cells placed in either random or ordered locations. The nuclei can be centered or eccentric. The new model provides insight into the micro level for differences in the trials. The differences arise from the tissue's cellular geometry and the effects of neighboring cells. These results help to explain the observed clinical outcomes. (authors)

  11. 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

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

    International Nuclear Information System (INIS)

    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)

  13. Neutron capture therapy

    International Nuclear Information System (INIS)

    The overall state of the art related with neutron capture therapy(NCT) is surveyed. Since the field related with NCT is very wide, it is not intended to survey all related subjects in depth. The primary objective of this report is to help those working for the installation of a NCT facility and a PGNAA(prompt gamma ray neutron activation analysis) system for the boron analysis understand overall NCT at Hanaro. Therefore, while the parts of reactor neutron source and PGNAA are dealt in detail, other parts are limited to the level necessary to understand related fields. For example, the subject of chemical compound which requires intensive knowledge on chemistry, is not dealt as a separated item. However, the requirement of a compound for NCT, currently available compounds, their characteristics, etc. could be understood through this report. Although the subject of cancer treated by NCT is out of the capability of the author, it is dealt focussing its characteristics related with the success of NCT. Each detailed subject is expected to be dealt more detail by specialists in future. This report would be helpful for the researchers working for the NCT to understand related fields. (author). 128 refs., 3 tabs., 12 figs

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

    International Nuclear Information System (INIS)

    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 10B 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 10B/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)

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

    International Nuclear Information System (INIS)

    Two new target concepts, NIFTI and DISCOS, that enable a large reduction in the proton beam current needed to produce epithermal neutrons for BNCT (Boron Neutron Capture Therapy) are described. In the NIFTI concept, high energy neutrons produced by (p, n) reactions of 2.5 MeV protons on Li are down scattered to treatment energies (∼ 20 keV) by relatively thin layers of PbF2 and iron. In the DISCOS concept, treatment energy neutrons are produced directly in a succession of thin (∼ 1 micron) liquid Li films on rotating Be foils. These foils interact with a proton beam that operates just above threshold for the (p, n) reaction, with an applied DC field to re-accelerate the proton beam between the target foils

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

    International Nuclear Information System (INIS)

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Hampel, G.; Grunewald, C.; Schutz, C.; Schmitz, T.; Kratz, J.V. [Nuclear Chemistry, University of Mainz, D-55099 Mainz (Germany); Brochhausen, C.; Kirkpatrick, J. [Department of Pathology, University of Mainz, D-55099 Mainz (Germany); Bortulussi, S.; Altieri, S. [Department of Nuclear and Theoretical Physics University of Pavia, Pavia (Italy); National Institute of Nuclear Physics (INFN) Pavia Section, Pavia (Italy); Kudejova, P. [Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Universitaet Muenchen, D-85748 Garching (Germany); Appelman, K.; Moss, R. [Joint Research Centre (JRC) of the European Commission, NL-1755 ZG Petten (Netherlands); Bassler, N. [University of Aarhus, Norde Ringade, DK-8000, Aarhus C (Denmark); Blaickner, M.; Ziegner, M. [Molecular Medicine, Health and Environment Department, AIT Austrian Institute of Technology GmbH (Austria); Sharpe, P.; Palmans, H. [National Physical Laboratory, Teddington TW11 0LW, Middlesex (United Kingdom); Otto, G. [Department of Hepatobiliary, Pancreatic and Transplantation Surgery, University of Mainz, D-55099 Mainz (Germany)

    2011-07-01

    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 in Pavia (Italy) a few years ago, where patients with liver metastases were treated by combining BNCT with auto-transplantation of the organ. Here, in Mainz, a preclinical trial has been started on patients suffering from liver metastases of colorectal carcinoma. In vitro experiments and the first animal tests have also been initiated to investigate radiobiological effects of radiation generated during BNCT. For both experiments and the treatment, a reliable dosimetry system is necessary. From work elsewhere, the use of alanine detectors appears to be an appropriate dosimetry technique. (author)

  19. 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.

  20. A case of radiation-induced osteosarcoma treated effectively by boron neutron capture therapy

    International Nuclear Information System (INIS)

    We treated a 54-year-old Japanese female with a recurrent radiation-induced osteosarcoma arising from left occipital skull, by reactor-based boron neutron capture therapy (BNCT). Her tumor grew rapidly with subcutaneous and epidural extension. She eventually could not walk because of cerebellar ataxia. The tumor was inoperable and radioresistant. BNCT showed a marked initial therapeutic effect: the subcutaneous/epidural tumor reduced without radiation damage of the scalp except hair loss and the patient could walk again only 3 weeks after BNCT. BNCT seems to be a safe and very effective modality in the management of radiation-induced osteosarcomas that are not eligible for operation and other treatment modalities

  1. FiR 1 Reactor in Service for Boron Neutron Capture Therapy (BNCT) and Isotope Production

    International Nuclear Information System (INIS)

    The FiR 1 reactor, a 250 kW Triga reactor, has been in operation since 1962. The main purpose to run the reactor is now the Boron Neutron Capture Therapy (BNCT). Although BNCT dominates the current utilization of the reactor, it also has an important national role in providing local enterprises and research institutions in the fields of industrial measurements, pharmaceuticals, electronics, etc. with isotope produc- tion and activation analysis services. The whole reactor building has been renovated, creating a dedicated clinical BNCT facility at the reactor. Close to 30 patients have been treated since May 1999, when the licence for patient treatment was granted to the responsible BNCT treatment organization. The treatment organization has a close connection to the Helsinki University Central Hospital. (author)

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

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) with Na2B12H11SH (BSH) or p-dihydroxyborylphenylalanine (BPA), and with a combination of both, was compared to radiotherapy with temozolomide, and the number of patients required to show statistically significant differences between the treatments was calculated. Whereas arms using BPA require excessive number of patients in each arm, a two-armed clinical trial with BSH and radiotherapy plus temozolomide is feasible. - Highlights: • BNCT of Glioblastoma with BPA is not more effective than RT+TMZ. • BNCT of Glioblastoma with BSH is probably more effective than RT+TMZ. • A clinical trial with patients of class V and an unmethylated MGMT gene should be conducted

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-04-30

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Gambarini, G.; Valente, M. [Department of Physics of the University and INFN, Via Celoria 16, I-20133 Milan (Italy); Moss, R.L.; Daquino, G.G.; Nievaart, V.A. [Joint Research Centre, Institute for Energy, P.O. Box 2, NL-1755ZG Petten, The Netherlands (Netherlands); Mariani, M.; Vanossi, E. [Department of Nuclear Engineering of Polytechnic, CESNEF, Via Ponzio, 34/3 - I-20133 Milan (Italy); Carrara, M. [Medical Physics Department, National Cancer Institute, Via Venezian 1, I-20131, Milan (Italy)

    2006-07-01

    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)

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

    Science.gov (United States)

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

    2009-12-10

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

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

    International Nuclear Information System (INIS)

    Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10B and thermal neutrons (10B+1n → 7Li+4He (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 (Na210B12H11SH; BSH) and borono-phenylalanine (10BPA) 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 10B 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 10B 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 10B carrier to obviate phagocytosis by reticuloendotherial systems. We had prepared 10BSH entrapped Water-in-Oil-in-Water (WOW) emulsion. The 10B concentration in VX-2 tumour after intra-arterial injection of 10BSH entrapped WOW emulsion was superior to the groups of 10BSH entrapped conventional Lipiodol mix emulsion. 10Boron entrapped WOW emulsion is one of the most useful for intra-arterial boron delivery carrier on BNCT to hepatocellular carcinoma. (author)

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

    International Nuclear Information System (INIS)

    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 ED50 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 ED50 to 14.7 ± 0.2 Gy and 15.5 ± 0.4 Gy, respectively. Thermal neutron irradiation in the presence of BPA resulted in an ED50 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 ED50 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

  8. Boron microquantification in oral mucosa and skin following administration of a neutron capture therapy agent

    Energy Technology Data Exchange (ETDEWEB)

    Kiger, S.W. III; Micca, P.L.; Morris, G.M.; Coderre, J.A

    2002-07-01

    Clinical trials of boron neutron capture therapy (BNCT) for intracranial tumours using boronphenylalanine-fructose undertaken at Harvard-MIT and Brookhaven National Laboratory have observed acute normal tissue reactions in the skin and oral mucosa. Because the range of the {sup 10}B(n,a){sup 7}Li reaction products is very short, 10-14 {mu}m combined, knowledge of the 10B microdistribution in tissue is critical for understanding the microdosimetry and radiobiology of BNCT. This paper reports measurements of the microdistribution of {sup 10}B in an animal model, rat skin and tongue, using high resolution quantitative autoradiography (HRQAR), a neutron-induced track etch autoradiographic technique. The steep spatial gradient and high absolute value relative to blood of the {sup 10}B concentration observed in some strata of the rat tongue epithelium and skin are important for properly evaluating the radiobiology and the biological effectiveness factors for normal tissue reactions such as oral mucositis, which are generally assessed using the blood boron concentration rather than the tissue boron concentration. (author)

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

    International Nuclear Information System (INIS)

    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

  10. 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

  11. Can epithermal boron neutron capture therapy treat primary and metastatic liver cancer?

    International Nuclear Information System (INIS)

    Full text: The poor prognosis of metastatic cancer to the liver calls for the investigation of alternative treatment modalities. This paper analyses the possible use of epithermal boron neutron capture therapy for the palliative treatment of these cancers. We examine possible treatment planning scenarios for selected tumour to liver boron ratios, and specifically for the epithermal beam at the HFR, Petten. It is required that a therapeutic ratio> 1 be achieved over the entire organ. Monte Carlo calculations were performed using the radiation transport code MCNP. The geometrical model used a 'variable voxel' technique to reconstruct an anthropomorphic phantom from CT scans. Regions of interest such as the liver were modelled to a resolution of a few millimetres, whereas surrounding regions were modelled with lesser detail thereby facilitating faster computation time. Three dimensional dose distributions were calculated for a frontal beam directed at the liver, and found to be in satisfactory agreement with measurements using bare and cadmium covered gold foils, PIN and MOSFET dosimeters for fast neutron and gamma measurements respectively. Dose distributions were calculated for orthogonal epithermal neutron beams to the front and side, using the parameters of the epithermal beam at Petten, and assumed tumour and normal tissue boron-10 concentrations of 30 ppm and 7.5 ppm boron-10 respectively. The therapeutic ratio (i e the dose to the tumour relative to the maximum dose to normal tissue) was found to be about 1.8, reducing to unity for the limiting condition of a tumour in the posterior liver. This result opens up the possibility of palliative therapy for the management of primary and metastatic liver cancer

  12. Design of a medical reactor generating high quality neutron beams for boron neutron capture therapy

    International Nuclear Information System (INIS)

    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, B-10, that are capable of preferentially accumulating in the tumor, which is then irradiated with thermal neutrons. The interaction of the B-10 with a thermal neutron causes the B-10 nucleus to split, releasing an alpha particle and a lithium nucleus. These products of the boron neutron capture reaction are very damaging to cells but have a path length in tissue of approximately 14 micrometers, or roughly the diameter of one or two cells. Thus, most of the ionizing energy imparted to tissue is localized to B-10-loaded cells. Since the early 1980s, there have been considerable improvements in boron compounds and neutron beams. More is known now about the radiation biology of BNCT, which has reemerged as a potentially useful method for preferential irradiation of tumors. Clinical trials have been initiated at BNL and MIT, with an improved boron compound and epithermal neutrons. At this time, nuclear reactors are the only demonstrated satisfactory sources of epithermal neutrons. While some reactors are available and within reach of cancer treatment centers, a question arises as to the feasibility and practicality of placing new epithermal neutron sources in hospitals. In this thesis, we design a square reactor (that can easily be reconfigured into polygonal reactors as the need arises) with four slab type assemblies to produce two epithermal neutron beams and two thermal neutron beams for use in neutron capture therapy. This square reactor with four large-area faces consists of 1056 U3Si-Al fuel elements and 36 B4C control rods. The proposed facility, based on this square reactor core with a maximum operating power of 300kW, provides an epithermal neutron beam of 3.2x109 nepi/cm2 · s intensity with low contamination by fast neutrons (<1.6x10-13 Gy · cm2/nepi) and gamma rays (<1.0x10-13 Gy · cm2/nepi

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

    International Nuclear Information System (INIS)

    The resulting neutron captures in 10B are used for radiation therapy. The occurrence point of the characteristic 478 keV prompt gamma rays agrees with the neutron capture point. If these prompt gamma rays are detected by external instruments such as a gamma camera or single photon emission computed tomography (SPECT), the therapy region can be monitored during the treatment using images. A feasibility study and analysis of a reconstructed image using many projections (128) were conducted. The optimization of the detection system and a detailed neutron generator simulation were beyond the scope of this study. The possibility of extracting a 3D BNCT-SPECT image was confirmed using the Monte Carlo simulation and OSEM algorithm. The quality of the prompt gamma ray SPECT image obtained from BNCT was evaluated quantitatively using three different boron uptake regions and was shown to depend on the location and size relations. The prospects for obtaining an actual BNCT-SPECT image were also estimated from the quality of the simulated image and the simulation conditions. When multi tumor regions should be treated using the BNCT method, a reasonable model to determine how many useful images can be obtained from SPECT can be provided to the BNCT facilities based on the preceding imaging research. However, because the scope of this research was limited to checking the feasibility of 3D BNCT-SPECT image reconstruction using multiple projections, along with an evaluation of the image, some simulation conditions were taken from previous studies. In the future, a simulation will be conducted that includes optimized conditions for an actual BNCT facility, along with an imaging process for motion correction in BNCT. Although an excessively long simulation time was required to obtain enough events for image reconstruction, the feasibility of acquiring a 3D BNCT-SPECT image using multiple projections was confirmed using a Monte Carlo simulation, and a quantitative image analysis was

  14. Gadolinium neutron capture therapy

    International Nuclear Information System (INIS)

    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. 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)

  16. 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.)

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Bortolussi, S; Altieri, S

    2007-12-01

    The selective uptake of boron by tumors compared to that by healthy tissue makes boron neutron capture therapy (BNCT) an extremely advantageous technique for the treatment of tumors that affect a whole vital organ. An example is represented by colon adenocarcinoma metastases invading the liver, often resulting in a fatal outcome, even if surgical resection of the primary tumor is successful. BNCT can be performed by irradiating the explanted organ in a suitable neutron field. In the thermal column of the Triga Mark II reactor at Pavia University, a facility was created for this purpose and used for the irradiation of explanted human livers. The neutron field distribution inside the organ was studied both experimentally and by means of the Monte Carlo N-particle transport code (MCNP). The liver was modeled as a spherical segment in MCNP and a hepatic-equivalent solution was used as an experimental phantom. In the as-built facility, the ratio between maximum and minimum flux values inside the phantom ((phi(max)/phi(min)) was 3.8; this value can be lowered to 2.3 by rotating the liver during the irradiation. In this study, the authors proposed a new facility configuration to achieve a uniform thermal neutron flux distribution in the liver. They showed that a phi(max)/phi(min) ratio of 1.4 could be obtained without the need for organ rotation. Flux distributions and dose volume histograms were reported for different graphite configurations. PMID:18196797

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

    International Nuclear Information System (INIS)

    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

  20. The effects of boron neutron capture therapy on liver tumors and normal hepatocytes in mice

    International Nuclear Information System (INIS)

    To explore the feasibility of employing boron neutron capture therapy (BNCT) to treat liver tumors, the effects of BNCT were investigated by using liver tumor models and normal hepatocytes in mice. Liver tumor models in C3H mice were developed by intrasplenic injection of SCCVII tumor cells. After borocaptate sodium (BSH) and boronophenylalanine (BPA) administration, 10B concentrations were measured in tumors and liver and the liver was irradiated with thermal neutrons. The effects of BNCT on the tumor and normal hepatocytes were studied by using colony formation assay and micronucleus assay, respectively. To compare the effects of BSH-BNCT and BPA-BNCT, the compound biological effectiveness (CBE) factor was determined. The CBE factors for BSH on the tumor were 4.22 and 2.29 using D10 and D0 as endpoints, respectively. Those for BPA were 9.94 and 5.64. In the case of hepatocytes, the CBE factors for BSH and BPA were 0.94 and 4.25, respectively. Tumor-to-liver ratios of boron concentration following BSH and BPA administration were 0.3 and 2.8, respectively. Considering the accumulation ratios of 10B, the therapeutic gain factors for BSH and BPA were 0.7-1.3 and 3.8-6.6, respectively. Therefore, it may be feasible to treat liver tumors with BPA-BNCT. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Do-Kun; Jung, Joo-Young; Suk Suh, Tae, E-mail: suhsanta@catholic.ac.kr [Department of Biomedical Engineering and Research Institute of Biomedical Engineering, College of Medicine, Catholic University of Korea, Seoul 505 137-701 (Korea, Republic of); Jo Hong, Key [Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, California 94305 (United States); Sil Lee, Keum [Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States)

    2015-01-15

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

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, H.E.

    1996-04-01

    Boron neutron capture therapy is an experimental binary cancer radiotherapy modality in which a boronated pharmaceutical that preferentially accumulates in malignant tissue is first administered, followed by exposing the tissue in the treatment volume to a thermal neutron field. Current usable beams are reactor-based but a viable alternative is the production of an epithermal neutron beam from an accelerator. Current literature cites various proposed accelerator-based designs, most of which are based on proton beams with beryllium or lithium targets. This dissertation examines the efficacy of a novel approach to BNCT treatments that incorporates an electron linear accelerator in the production of a photoneutron source. This source may help to resolve some of the present concerns associated with accelerator sources, including that of target cooling. The photoneutron production process is discussed as a possible alternate source of neutrons for eventual BNCT treatments for cancer. A conceptual design to produce epithermal photoneutrons by high photons (due to bremsstrahlung) impinging on deuterium targets is presented along with computational and experimental neutron production data. A clinically acceptable filtered epithermal neutron flux on the order of 10{sup 7} neutrons per second per milliampere of electron current is shown to be obtainable. Additionally, the neutron beam is modified and characterized for BNCT applications by employing two unique moderating materials (an Al/AlF{sub 3} composite and a stacked Al/Teflon design) at various incident electron energies.

  4. Epithermal neutron beam adoption for liver cancer treatment by boron and gadolinium neutron capture therapy

    International Nuclear Information System (INIS)

    Comparative evaluation was made on depth-dose distribution in boron neutron capture therapy (B-NCT) and gadolinium one (Gd-NCT) for the treatments of liver cancers. At present, epithermal neutron beam is expected to be applicable to the treatment of deep and widespread tumors. ICRU computational model of ADAM and EVA was used as a liver phantom loading a tumor at depth of 6 cm in its central region. Epithermal neutron beam of Musashi reactor was used as the primary neutron beam for the depth-dose calculation. Calculation was conducted using the three-dimensional continuous-energy Monte Carlo code MCNP4A. The doses observed in both NCTs were bumped over the tumor region but the dose for Gd-NCT was not so tumor-specific compared with that for BNCT because radiation in Gd-NCT was due to γ-ray. The mean physical dose was 4 Gy/h for boron 30 ppm and 5 Gy/h for Gd 1000 ppm when exposed to an epithermal neutron flux of 5x108 n/cm-2/sec and the dose ratio of tumor-to normal tissue was 2.7 for boron and 2.5 for Gd. The lethal dose of 50 Gy for the liver can be accomplished under conditions where the dose has not reached 25 Gy, the tolerance dose of the normal tissue. This seems very encouraging and indicating that both B-NCT and Gd-NCT are applicable for the treatment for liver cancer. However, if normal tissue contain 1/4 of the tumor concentration of boron or Gd, the BNCT would still possible when considering a large RBE value for 10B(n, α) reaction but the Gd-NCT would impossible for deep liver treatment. (M.N.)

  5. 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.

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

    International Nuclear Information System (INIS)

    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 10B, 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 10B 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 10B 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.

  7. Neutron capture therapy for melanoma

    International Nuclear Information System (INIS)

    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

  8. Enhanced therapeutic effect on murine melanoma and angiosarcoma cells by boron neutron capture therapy using a boronated metalloporphyrin

    International Nuclear Information System (INIS)

    We have already achieved successful treatment of several human patients with malignant melanoma by boron neutron capture therapy (BNCT) using 10B1-paraboronophenylalanine (10B1-BPA·HCl). In this study we used a new compound, a manganese boronated protoporphyrin (Mn-10BOPP), and compared it to 10B1-BPA·HCl with respect to uptake in murine melanoma and angiosarcoma cells as well as to their cell killing effect. 10B uptake was measured in a new method, and the new compound was much more incorporated into both cells than 10B1-BPA·HCl. Furthermore, melanoma and angiosarcoma cells preincubated with the new compound were 15 to 20 times more efficiently killed by BNCT than cells preincubated with 10B1-BPA·HCl. (author)

  9. Physical and tumor biological aspects and calculation model of dosage in boron neutron capture therapy (BNCT)

    Energy Technology Data Exchange (ETDEWEB)

    Rassow, J.; Poeller, F.; Meissner, P. (Essen Univ. (Gesamthochschule) (Germany). Abt. fuer Medizinische Strahlenphysik); Steinberg, F. (Essen Univ. (Gesamthochschule) (Germany). Inst. fuer Medizinische Strahlenbiologie)

    1993-01-01

    Fundamentally different aspects apply to dosage in boron neutron capture therapy (BNCT) compared to that in the case of normal radiotherapy with photons, electrons or heavy particles such as neutrons. The reason is that the latter only requires a knowledge of the stochastic distribution of the absorbed dose within cells, radiation quality and atomic composition of tissue in the regions of interest, whereas for the former the absolute concentration and microscopic distribution of [sup 10]B atoms in inter- and intracellular spaces of tumor and healthy cells is additionally of equal importance. The effects of radiation without [sup 10]B must always be superimposed on those of heavy particles resulting from neutron capture reactions on [sup 10]B atoms. Complex geometrical calculaations are necessary with respect to ranges of the heavy particles smaller than a cell diameter. Apart from the direct effects of radiation without [sup 10]B, the dosage therefore depends on thermal neutron fluence, [sup 10]B concentration, its extreme inhomogeneous macroscopic distribution in the tumor tissue, the cellular localization of the [sup 10]B atoms in the large intercellular space, the cell membrane, within cytoplasm or the cell nucleus, the geometrical probability of hitting the cell nucleus, and that such a hit finally results in a cell killing, and a Poisson statistical enhancement factor, which describes the dose-effect relation for cell survival. The calculations necessary are demonstrated in the case of a normal and a tumor cell type, each with representative cell diameter and nucleus size. It is evident that the microscopic distribution of [sup 10]B atoms is one of the most critical parameters which is still insufficiently known. (orig.).

  10. Design of neutron beams for boron neutron capture therapy in a fast reactor

    International Nuclear Information System (INIS)

    The BNCT (Boron Neutron Capture Therapy) technique makes use of thermal or epithermal neutrons to irradiate tumours previously loaded with 10B. Reactors are currently seen as a suitable neutron source for BNCT implementation, due to the high intensity of the flux they can provide. The TAPIRO reactor, that is located at the ENEA Casaccia Centre near Rome, is a low-power fast-flux research reactor that can be usefully employed for this application. In this work computer simulations were carried out on this reactor to obtain epithermal and thermal neutron beams for the application of BNCT in Italy in the framework of a specific research program. Comparisons with measurements are also reported. Using the MCNP-4B code, Monte Carlo calculations were carried out to determine the materials suitable for the design of the thermal and epithermal columns. Various arrangements of reflector and moderator materials have been investigated to achieve the desired experimental constraints. On the basis of these calculations, a thermal column was designed and installed in the TAPIRO reactor to perform preliminary experiments on small laboratory animals. For the planning of a therapy treatment of gliomas on larger size animals, several material configurations were investigated in the search for an optimal epithermal facility. The aim of the present study is to indicate how a fast research reactor can be successfully modified for generating neutron beams suitable for BNCT applications. (author)

  11. Indication and possibility of boron neutron capture therapy in head and neck cancer

    International Nuclear Information System (INIS)

    Background: Boron neutron capture therapy (BNCT) is a targeted type of radiotherapy that has a number of significant advantages over conventional external beam photon irradiation, especially in that radiation can be selectively delivered to tumor cells. We had, first in the world, treated with BNCT for a patient with recurrent head and neck cancer (HNC) in 2001. Methods : From December, 2001 to February, 2013, we had treated 37 patients with recurrent HNC by means of 54 applications of BNCT at Kyoto University Research Reactor Institute (KURRI) and Japan Atomic Energy Agency (JAEA). All of them had received standard therapy and subsequently developed recurrent disease for which there were no other treatment options. Results : All of the (1) Regression rates were complete response (CR) : 19 patients (51%), partial response (PR) : 14(38%), progressive disease (PD) : 3(8%), and not evaluated (NE) : 1(3%) patient. (2) The overall patient response rate was 91%, though all the patients had advanced disease. The 4-year and 7-year OS rates were 42% and 36%, respectively. (3) BNCT improved quality of life (QOL), performance status (PS) and survival times. (4) The primary adverse events were brain necrosis, osteomyelitis and transient mucositis and alopecia. Conclusions : Our results indicate that we could make sure that safety and effectiveness of BNCT, and BNCT represents a new and promising treatment modality in patients for whom there are no other treatment options. (author)

  12. Boron neutron capture therapy for advanced salivary gland carcinoma in head and neck

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is a among the radiation treatments known to have a selective lethal effect on tumor cells. This study summarizes the tumor responses and the acute and late adverse effects of BNCT in the treatment of patients with both recurrent and newly diagnosed T4 salivary gland carcinoma. Two patients with recurrent cancer and 3 with newly diagnosed T4 advanced malignancy were registered between October 2003 and September 2007, with the approval of the medical ethics committees of Kawasaki Medical School and Kyoto University. BNCT was performed, in a single fraction using an epithermal beam, at Japan Research Reactor 4. All patients achieved a complete response within 6 months of treatment. The median duration of the complete response was 24.0 months; the median overall survival time was 32.0 months. Three of the 5 patients are still alive; the other 2 died of distant metastatic disease. Open biopsy of the parotid gland after BNCT was performed in 1 patient and revealed no residual viable cancer cells and no serious damage to the normal glandular system. Although mild alopecia, xerostomia, and fatigue occurred in all patients, there were no severe adverse effects of grade 3 or greater. Our preliminary results demonstrate that BNCT is a potential curative therapy for patients with salivary gland carcinoma. The treatment does not cause any serious adverse effects, and may be used regardless of whether the primary tumor has been previously treated. (author)

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

    International Nuclear Information System (INIS)

    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)

  14. Insights into the use of gadolinium and gadolinium/boron-based agents in imaging-guided neutron capture therapy applications.

    Science.gov (United States)

    Deagostino, Annamaria; Protti, Nicoletta; Alberti, Diego; Boggio, Paolo; Bortolussi, Silva; Altieri, Saverio; Crich, Simonetta Geninatti

    2016-05-01

    Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with (10)B, known as boron neutron capture therapy (BNCT), a binary treatment combining neutron irradiation with the delivery of boron-containing compounds to tumors. Currently, the use of Gd for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd- and B-Gd-containing compounds with the task of finding the best systems able to improve the NCT clinical outcome. PMID:27195428

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

    International Nuclear Information System (INIS)

    Alpha-particle and recoil Li atom yielded by the reaction (10B, 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, and

  16. Medical chemistry of boron neutron capture agents having pharmacological activity

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is a cancer treatment that selectively destroys cancer cells following administering a cancer-selective drug containing stable isotope boron-10 and neutron irradiation. In clinical trial of BNCT, disodium mercaptoundecahydro-closo-dodecaborate (BSH) and p-boronophenylalanine (BPA) have been used, however, development of a new drugs with high cancer selectivity and therapeutic efficiency is expected. Therefore, we review boron-containing drugs as a boron neutron capture agents having pharmacological activity, BNCT research on boron-modified porphyrin derivatives which have photosensitivity and neutron capture activity and our proposed neutron sensitizing agent. (author)

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

    Science.gov (United States)

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

    2016-03-01

    Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4-/- p53-/- and Lig4+/+ p53-/- to irradiation using a thermal neutron beam in the presence or absence of (10)B-para-boronophenylalanine (BPA). The Lig4-/- p53-/- cell line had a higher sensitivity than the Lig4+/+ p53-/-cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that (10)B uptake was higher in the Lig4+/+ p53-/- than in the Lig4-/- p53-/- cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV. PMID:26573366

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

    International Nuclear Information System (INIS)

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

  19. 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.

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

    International Nuclear Information System (INIS)

    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 39mm3 in BNCT-treated group, and 138 mm3 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)

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

    Science.gov (United States)

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

    2009-08-01

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

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

    International Nuclear Information System (INIS)

    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) 10B 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.

  3. Epithermal neutron formation for boron neutron capture therapy by adiabatic resonance crossing concept

    International Nuclear Information System (INIS)

    Low-energy protons from the cyclotron in the range of 15–30 MeV and low current have been simulated on beryllium (Be) target with a lead moderator around the target. This research was accomplished to design an epithermal neutron beam for Boron Neutron Capture Therapy (BNCT) using the moderated neutron on the average produced from 9Be target via (p, xn) reaction in Adiabatic Resonance Crossing (ARC) concept. Generation of neutron to proton ratio, energy distribution, flux and dose components in head phantom have been simulated by MCNP5 code. The reflector and collimator were designed in prevention and collimation of derivation neutrons from proton bombarding. The scalp-skull-brain phantom consisting of bone and brain equivalent material has been simulated in order to evaluate the dosimetric effect on the brain. Results of this analysis demonstrated while the proton energy decreased, the dose factor altered according to filters thickness. The maximum epithermal flux revealed using fluental, Fe and bismuth (Bi) filters with thicknesses of 9.4, 3 and 2 cm, respectively and also the epithermal to thermal neutron flux ratio was 103.85. The potential of the ARC method to replace or complement the current reactor-based supply sources of BNCT purposes. (author)

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

    International Nuclear Information System (INIS)

    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 FluentalTM (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)

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

    International Nuclear Information System (INIS)

    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 10B 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)

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

    International Nuclear Information System (INIS)

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

  7. Boron Neutron Capture Therapy at IRT -Sofia Research Reactor. Basics and activities

    International Nuclear Information System (INIS)

    The Boron Neutron Capture Therapy (BNCT) proved itself to be vital option for severe cancer treatment during the last 20 years. The building of BNCT facility was a main task of the reconstruction of the IRT-Sofia research reactor at the Institute for Nuclear Research and Nuclear Energy of the Bulgarian Academy of Sciences. A number of activities in the development of appropriate infrastructure including accumulation of the existing experience, and creation of a multidisciplinary team and infrastructure, collecting BNCT oriented information in the IT-system was done. The technical design of the BNCT irradiation channel followed the beam tube configuration of the reactor at the Massachusetts Institute of Technology, USA, and took also into account the limits of the reactor construction geometry. The results of neutron and gamma transport calculations performed for the reactor model showed that the facility would be able to supply epithermal neutron flux with quality, equal to the best values reached in the world until now. The BNCT will play a significant role in the sustainable utilization of the reactor for cancer treatment of patients from the Balkan region. (authors)

  8. 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...

  9. Whole-body dose evaluation with an adaptive treatment planning system for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Dose evaluation for out-of-field organs during radiotherapy has gained interest in recent years. A team led by University of Tsukuba is currently implementing a project for advancing boron neutron capture therapy (BNCT), along with a radiation treatment planning system (RTPS). In this study, the authors used the RTPS (the 'Tsukuba-Plan') to evaluate the dose to out-of-field organs during BNCT. Computed tomography images of a whole-body phantom were imported into the RTPS, and a voxel model was constructed for the Monte Carlo calculations, which used the Particle and Heavy Ion Transport Code System. The results indicate that the thoraco-abdominal organ dose during BNCT for a brain tumour and maxillary sinus tumour was 50-360 and 120-1160 mGy-Eq, respectively. These calculations required ∼29.6 h of computational time. This system can evaluate the out-of-field organ dose for BNCT irradiation during treatment planning with patient-specific irradiation conditions. (authors)

  10. A novel reactor concept for boron neutron capture therapy: annular low-low power reactor (ALLPR)

    Energy Technology Data Exchange (ETDEWEB)

    Petrovic, B.; Levine, S.H. [Department of Nuclear Engineering, Pennsylvania State University, University Park, PA 16802 (United States)

    1998-07-01

    Boron Neutron Capture Therapy (BNC), originally proposed in 50's, has been getting renewed attention over the last {approx}10 years. This is in particular due to its potential for treating deep-seated brain tumors by employing epithermal neutron beams. Large (several MW) research reactors are currently used to obtain epithermal beams for BNCT, but because of cost and licensing issues it is not likely that such high-power reactors can be placed in regular medical centers. This paper describes a novel reactor concept for BNCT devised to overcome this obstacle. The design objective was to produce a beam of epithermal neutrons of sufficient intensity for BNCT at <50 kW using low enriched uranium. It is achieved by the annular reactor design, which is called Annular Low-Low Power Reactor (ALLPR). Preliminary studies using Monte Carlo simulations are summarized in this paper. The ALLPR should be relatively economical to build, and safe and easy to operate. This novel concept may increase the viability of using BNCT in medical centers worldwide. (author)

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    Full text: Introduction: Boron neutron capture therapy (BNCT) is an experimental radiotherapy where a compound having 10B is administered to cancer patients and is accumulated in tumor tissues. Thus, the tumor is irradiated with thermal neutrons, 10B 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 reduction

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

    Science.gov (United States)

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

    2005-12-01

    An international collaboration was organized to undertake a dosimetry exchange to enable the future combination of clinical data from different centers conducting neutron capture therapy trials. As a first step (Part I) the dosimetry group from the Americas, represented by MIT, visited the clinical centers at Studsvik (Sweden), VTT Espoo (Finland), and the Nuclear Research Institute (NRI) at Rez (Czech Republic). A combined VTT/NRI group reciprocated with a visit to MIT. Each participant performed a series of dosimetry measurements under equivalent irradiation conditions using methods appropriate to their clinical protocols. This entailed in-air measurements and dose versus depth measurements in a large water phantom. Thermal neutron flux as well as fast neutron and photon absorbed dose rates were measured. Satisfactory agreement in determining absorbed dose within the experimental uncertainties was obtained between the different groups although the measurement uncertainties are large, ranging between 3% and 30% depending upon the dose component and the depth of measurement. To improve the precision in the specification of absorbed dose amongst the participants, the individually measured dose components were normalized to the results from a single method. Assuming a boron concentration of 15 microg g(-1) that is typical of concentrations realized clinically with the boron delivery compound boronophenylalanine-fructose, systematic discrepancies in the specification of the total biologically weighted dose of up to 10% were apparent between the different groups. The results from these measurements will be used in future to normalize treatment plan calculations between the different clinical dosimetry protocols as Part II of this study. PMID:16475772

  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. Tumor cell killing effect of boronated dipeptide. Boromethylglycylphenylalanine on boron neutron capture therapy for malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Takagaki, Masao; Ono, Koji; Masunaga, Shinichiro; Kinashi, Yuko; Kobayashi, Toru [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.; Oda, Yoshifumi; Kikuchi, Haruhiko; Spielvogel, B.F.

    1994-03-01

    The killing effect of Boron Neutron Capture Therapy; BNCT, is dependant on the boron concentration ratio of tumor to normal brain (T/N ratio), and also that of tumor to blood (T/B ratio). The clinical boron carrier of boro-captate (BSH) showed the large T/N ratio of ca. 8, however the T/B ratio was around 1, which indicated nonselective accumulation into tumor. Indeed high boron concentration of blood restrict the neutron irradiation dose in order to circumvent the normal endothelial damage, especially in the case of deeply seated tumor. Phenylalanine analogue of para borono-phenylalanine (BPA) is an effective boron carrier on BNCT for malignant melanoma. For the BNCT on brain tumors, however, BPA concentration in normal brain was reported to be intolerably high. In order to improve the T/N ratio of BPA in brain, therefore, a dipeptide of boromethylglycylphenylalanine (BMGP) was synthesized deriving from trimethylglycine conjugated with BPA. It is expected to be selectively accumulated into tumor with little uptake into normal brain. Because a dipeptide might not pass through the normal blood brain barrier (BBB). Its killing effect on cultured glioma cell, T98G, and its distribution in rat brain bearing 9L glioma have been investigated in this paper. The BNCT effect of BMGP on cultured cells was nearly triple in comparison with DL-BPA. The neutron dose yielding 1% survival ratio were 7x10{sup 12}nvt for BMGP and 2x10{sup 13}nvt for BPA respectively on BNCT after boron loading for 16 hrs in the same B-10 concentration of 20ppm. Quantitative study of boron concentration via the {alpha}-auto radiography and the prompt gamma ray assay on 9L brain tumor rats revealed that T/N ratio and T/B ratio are 12.0 and 3.0 respectively. Those values are excellent for BNCT use. (author).

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    The radiobiology of the dose components in a BNCT exposure is examined. The effect of exposure time in determining the biological effectiveness of γ-rays, due to the repair of sublethal damage, has been largely overlooked in the application of BNCT. Recoil protons from fast neutrons vary in their relative biological effectiveness (RBE) as a function of energy and tissue endpoint. Thus the energy spectrum of a beam will influence the RBE of this dose component. Protons from the neutron capture reaction in nitrogen have not been studied but in practice protons from nitrogen capture have been combined with the recoil proton contribution into a total proton dose. The relative biological effectiveness of the products of the neutron capture reaction in boron is derived from two factors, the RBE of the short range particles and the bio-distribution of boron, referred to collectively as the compound biological effectiveness factor. Caution is needed in the application of these factors for different normal tissues and tumors. - Highlights: ► Radiobiological properties of different dose components in BNCT are considered. ► Effectiveness of γ-ray dose depends strongly on exposure time due to sublethal damage repair. ► Effectiveness of fast neutron dose depends on neutron energy spectrum. ► γ-ray and fast neutron characteristics vary between beams and thus weighting factors will differ. ► Weighing factors for boron dose depend on the carrier, the tissue and its mode of administration.

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

    International Nuclear Information System (INIS)

    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

  19. 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.

  20. Three-dimensional radiation dose distribution analysis for boron neutron capture therapy

    International Nuclear Information System (INIS)

    This paper reports that calculation of physically realistic radiation dose distributions for boron neutron capture therapy (BNCT) is a complex, three-dimensional problem. Traditional one-dimensional (slab) and two-dimensional (cylindrical) models, while useful for neutron beam design and performance analysis, do not provide sufficient accuracy for actual clinical use because the assumed symmetries inherent in such models do not ordinarily exist in the real world. Fortunately, however, it is no longer necessary to make these types of simplifying assumptions. Recent dramatic advances in computing technology have brought full three-dimensional dose distribution calculations for BNCT into the realm of practicality for a wide variety of routine applications. Once a geometric model and the appropriate material compositions have been determined, either stochastic (Monte Carlo) or deterministic calculations of all dose components of interest can now be performed more rapidly and inexpensively for the true three-dimensional geometries typical of actual clinical applications of BNCT. Demonstrations of both Monte Carlo and Deterministic techniques for performing three-dimensional dose distribution analysis for BNCT are provided. Calculated results are presented for a three-dimensional Lucite canine-head phantom irradiated in the epithermal neutron beam available at the Brookhaven Medical Research Reactor. The deterministic calculations are performed using the three-dimensional discrete ordinates method. The Monte Carlo calculations employ a novel method for obtaining spatially detailed radiation flux and dose distributions without the use of flux-at-a-point estimators. The calculated results are in good agreement with each other and with thermal neutron flux measurements taken using copper-gold flux wires placed at various locations in the phantom

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

    International Nuclear Information System (INIS)

    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 252Cf 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 252Cf 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 252Cf brachytherapy are presented in this paper. (author)

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

    International Nuclear Information System (INIS)

    Background: 7Li (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 7Li(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 7Li(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 7Li(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)

  3. 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)

  4. Growth inhibition of human pancreatic cancer grafts in nude mice by boron neutron capture therapy

    International Nuclear Information System (INIS)

    Cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between 10B and thermal neutrons to release alpha-particles (4He) and lithium-7 ions (7Li). The 4He kills cells in the range of 10 μm from the site of 4He generation. Therefore, it is theoretically possible to kill tumor cells without affecting adjacent healthy tissues, if 10B-compounds could be selectively delivered. We have described that 10B atoms delivered by immunoliposomes exerted cytotoxic effect on human pancreatic carcinoma cells (AsPC-1) in a dose-dependent manner by thermal neutron irradiation in vitro as reported previously. In the present study, the cytotoxic effect of a locally injected 10B compound solution or multilamellar liposomes containing a 10B compound to human pancreatic carcinoma xenograft in nude mice was evaluated after thermal neutron irradiation. AsPC-1 cells (1 x 107) injected subcutaneously into a nude mouse grew to a tumor weighing 100-300 mg after 2 weeks. At this time 200 μg 10B compounds was locally injected in the tumor and irradiated with 2 x 1012 n/cm2 thermal neutron. Tumor growth of 10B-treated groups was suppressed as compared with control group. Histopathologically, hyalinization and necrosis were found in the tumor tissues. For effective tumor destruction, 10B dose more than 60 μg was necessary. The tumor tissue injected with saline only and irradiated showed neither destruction nor necrosis. These data indicate that the accumulation of 10B atoms to the tumor site is mandatory for the cytotoxic effect by thermal neutron irradiation. (author)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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)

  8. 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.

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

    International Nuclear Information System (INIS)

    10B-Enriched borocaptate (BSH) was administered intraperitoneally to SCCVII tumor-bearing C3H/He mice. Electroporation (EP) was conducted by using a tweezers-type electrode. The 10B contents in tumors were measured by prompt γ-ray spectrometry. The colony formation assay was applied to investigate the antitumor effects of boron neutron capture therapy (BNCT) and thereby to estimate the intratumor localization of BSH. The 10B concentrations in tumors decreased with time following BSH administration, falling to 5.4(±0.1) ppm at 3 h, whereas EP treatment (3 repetitions) 15 min after BSH injection delayed the clearance of BSH from tumors, and the 10B level remained at 19.4(±0.9) ppm at 3 h. The effect of BNCT increased with the 10B concentration in tumors, and the combination with EP showed a remarkably large cell killing effect even at 3 h after BSH injection. The effect of BNCT, i.e., slope coefficient of the cell survival curve of tumors, without EP was proportional to tumor 10B level (r=0.982), and that of BSH-BNCT combined with EP lay close to the same correlation line. However, tumors subjected to EP after BSH injection did not show high radiosensitivity when irradiated after conversion to a single cell suspension by enzymatic digestion. This indicates that the increase of the BNCT effect by EP was a consequence of enclosure of BSH in the interstitial space of tumor tissue and not within tumor cells. This is different from a previous in vitro study. The combination of EP and BNCT may be clinically useful, if a procedure to limit EP to the tumor region becomes available or if an alternative similar method is employed. (author)

  10. 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)

    Purpose: A cooperative study in Europe and Japan was conducted to determine the pharmacokinetics and boron uptake of sodium borocaptate (BSH: Na2B12H11SH), 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 Tadj and the interval from BSH infusion to tumor tissue sampling. About 12-19 h after infusion, the actual values for Tadj 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

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

    International Nuclear Information System (INIS)

    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)

  12. {sup 1}H and {sup 10}B NMR and MRI investigation of boron- and gadolinium-boron compounds in boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bonora, M., E-mail: marco.bonora@unipv.it [Physics Department ' A. Volta' , University of Pavia, Via Bassi 6, 27100 Pavia (Italy)] [CNISM Unit (Italy); Corti, M.; Borsa, F. [Physics Department ' A. Volta' , University of Pavia, Via Bassi 6, 27100 Pavia (Italy)] [CNISM Unit (Italy); Bortolussi, S.; Protti, N.; Santoro, D.; Stella, S.; Altieri, S. [Nuclear and Theoretical Physics Department, University of Pavia, Via Bassi 6, 27100 Pavia (Italy)] [INFN Pavia (Italy); Zonta, C.; Clerici, A.M.; Cansolino, L.; Ferrari, C.; Dionigi, P. [Surgical Sciences Department, Experimental Surgery Laboratory, University of Pavia, Pavia (Italy); Porta, A.; Zanoni, G.; Vidari, G. [Organic Chemistry Department, University of Pavia, Via Taramelli 10, 27100 Pavia (Italy)

    2011-12-15

    {sup 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 {sup 1}H and {sup 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.

  13. 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.

  14. Workshop on neutron capture therapy

    International Nuclear Information System (INIS)

    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. Modelling collimator of radial beam port Kartini reactor for boron neutron capture therapy

    International Nuclear Information System (INIS)

    One of the cancer therapy methods is BNCT (Boron Neutron Capture Therapy). BNCT utilizes neutron nature by 10B deposited on cancer cells. The superiority of BNCT compared to the radiation therapy is the high level of selectivity since its level is within cell. This study was carried out on collimator modelling in radial beam port of reactor Kartini for BNCT. The modelling was conducted by simulation using software of Monte Carlo N-Particle version 5 (MCNP 5). MCNP5 is a package of the programs for both simulating and calculating the problem of particle transport by following the life cycle of a neutron since its birth from fission reaction, transport on materials, until eventually lost due to the absorption reaction or out from the system. The collimator modelling used materials which varied in size in order to generate the value of each of the parameters in accordance with the recommendation of the IAEA, the epithermal neutron flux (ϕepi) > 1.0 x 109n.cm-2s-1, the ratio between the neutron dose rate fast and epithermal neutron flux (Df/ϕepi) < 2.0 x 10-13 Gy.cm2.n-1, the ratio of gamma dose rate and epithermal neutron flux (Dγ/ϕepi) < 2.0 X10-13 Gy.cm2.n-1, the ratio between the thermal and epithermal neutron flux (ϕTh/ϕepi)< 0.05 and the ratio between the current and flux of the epithermal neutron (J/ϕepi) > 0.7. Based on the results of the optimization of the modeling, the materials and sizes of the collimator construction obtained were 0.75 cm Ni as collimator wall, 22 cm Al as a moderator and 4.5 cm Bi as a gamma shield. The outputs of the radiation beam generated from collimator modeling of the radial beam port were ϕepi = 5.25 x 106 n.cm-2.s-1, Df/ϕepi = 1.17 x 10-13Gy.cm2.n-1, Dγ/ϕepi = 1.70 x 10-12 Gy.cm2.n-1, ϕTh/ϕepi = 1.51 and J/ϕepi = 0.731. Based on this study, the result of the beam radiation coming out of the radial beam port dis not fully meet the criteria recommended by IAEA so need to continue this study to get the criteria of IAEA

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

    International Nuclear Information System (INIS)

    Full text: 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). The BNCT work dominates the current utilization of the reactor: three or four days per week are reserved for BNCT purposes and the rest for other purposes such as isotope production and neutron activation analysis. In the 1990's a BNCT treatment facility was build at the FiR1 reactor located at Technical Research Centre of Finland. A special new neutron moderator material FluentalTM (Al+AlF3+Li) developed at VTT ensures the superior quality of the neutron beam. Also the treatment environment is of world top quality. The ground floor of the reactor hall was provided with a new entrance, easily accessible by any patient vehicle, a radio therapy control room and rooms for patient preparation and laboratories. The top of the reactor tank was separated from the reactor hall in order to confine contamination in case of a leakage from irradiation samples or fuel elements. The ventilation of the building, emergency power supply system, heat exchangers and the secondary cooling circuit of the reactor including cooling towers were completely redesigned and rebuilt. The expenditure of designing and accomplishing the construction work described was about 4 million euros. The costs were partly financed with venture capital via Radtek Ltd., particularly established for this enterprise. Close to 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. VTT as the reactor operator has a long term contract with the Boneca Corp. to provide the facility and irradiation services for the patient treatments. The BNCT facility has been licensed for clinical use and is being surveyed by several national public health authorities including the Finnish Nuclear and Radiation Safety

  17. Potential of para-boronophenylalaninol as a boron carrier in boron neutron capture therapy, referring to that of its enantiomers

    International Nuclear Information System (INIS)

    We evaluated the potential of a newly developed 10B-containing alpha-amino alcohol of para-boronophenylalanine-10B (BPA), para-boronophenylalaninol (BPAol), as a boron carrier in boron neutron capture therapy. C57BL mice bearing EL4 tumors and C3H/He mice bearing SCC VII tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously via implanted mini-osmotic pumps to label all proliferating (P) cells. After oral administration of L-BPA or D-BPA, or intraperitoneal injection of L-BPAol or D-BPAol, the tumors were irradiated with reactor thermal neutron beams. For the combination with mild temperature hyperthermia (MTH) and/or tirapazamine (TPZ), the tumors were heated at 40 degrees centigrade for 30 minutes right before neutron exposure, and/or TPZ was intraperitoneally injected 30 minutes before irradiation. The tumors were then excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling ( = quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 hours after irradiation, tumor cell suspensions obtained in the same manner were used for determining the apoptosis frequency in Q cells. The apoptosis and MN frequency in total (P + Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Without TPZ or MTH, L- and D-BPAol increased both frequencies markedly, especially for total cells. Although not significantly, L-BPA and D-BPAol increased both frequencies slightly more remarkably than D-BPA and L-BPAol, respectively. On combined treatment with both MTH and TPZ, the sensitivity difference between total and Q cells was markedly reduced. MTH increased the 10B uptake of all 10B-carriers into both tumor cells to some degree. Both L- and D-BPAol have potential as 10B-carriers in neutron capture therapy, especially when combined with both MTH and TPZ

  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. Dynamic infrared imaging of the skin reaction in melanoma patients treated with boron neutron capture therapy

    International Nuclear Information System (INIS)

    As part of the Boron Neutron Capture Therapy (BNCT) project conducted jointly by the Comision Nacional de Energia Atomica and the oncology institute A. Roffo, Argentina, we have recently started a program designed to investigate the ability of dynamic infrared imaging for following-up our cutaneous melanoma patients. BNCT offers a unique opportunity to study the response of the integumentary system to single fractions and high doses of neutrons and heavy ions, providing information that could be potentially important in radiation accidents for people exposed to these kinds of radiation fields. Medical infrared thermography is a non-invasive and functional imaging method, that provides information on the normal and abnormal status and response of the nervous and vascular systems, as well as the local metabolic rate and inflammatory processes that appear as differences in the skin infrared emission. Although it is highly sensitive, it is unspecific, like other conventional imaging techniques. For this reason, infrared thermography must be employed as an adjunct method to other diagnostic procedures and the clinical observation. An infrared camera is employed, with an uncooled ferroelectric focal plane array of 320x240 detector elements, providing a video signal of the infrared emission in the 8-14 μm wavelength band. After patient preparation and acclimation, a basal study of the irradiated region is performed, including high and low dose areas, as well as normal and tumor tissues, and eventually other detectable structures (e.g. scars and veins). Thereafter, a provocation test (a cold stimulus) is applied and the temperature recovery is registered as a function of time. In addition, a 3D computational dosimetry of the irradiated region is performed, which allows a complete representation of the isodose contours mapped onto the 3D reconstruction representing the skin. This reconstruction permits selecting regions of different doses for studying the local response

  20. Development of a Tandem-ElectroStatic-Quadrupole accelerator facility for Boron Neutron Capture Therapy (BNCT)

    International Nuclear Information System (INIS)

    There is a generalized perception that the availability of suitable particle accelerators installed in hospitals, as neutron sources, may be crucial for the advancement of Boron Neutron Capture Therapy (BNCT). An ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT is described here. The project goal is a machine capable of delivering 30 mA of 2.4-2.5 MeV protons to be used in conjunction with a neutron production target based on the 7Li(p,n)7Be reaction slightly beyond its resonance at 2.25 MeV. A folded tandem, with 1.20-1.25 MV terminal voltage, combined with an ESQ chain is being designed and constructed. This machine is conceptually shown to be capable of accelerating a 30 mA proton beam to 2.5 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the 7Li(p,n)7Be reaction, to perform BNCT treatment for deep-seated tumors in less than an hour. This electrostatic machine is one of the technologically simplest and cheapest solutions for optimized AB-BNCT. At present there is no BNCT facility in the world with the characteristics presented in this work. For the accelerator, results on its design, construction and beam transport calculations are discussed. Taking into account the peculiarities of the expected irradiation field, the project also considers a specific study of the treatment room. This study aims at the design of the treatment room emphasizing aspects related to patient, personnel and public radiation protection; dose monitoring; patient positioning and room construction. The design considers both thermal (for the treatment of shallow tumors) and epithermal (for deep-seated tumors) neutron beams entering the room through a port connected to the accelerator via a moderation and neutron beam shaping assembly. Preliminary results of dose calculations for the treatment room design, using the MCNP program, are presented

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

    International Nuclear Information System (INIS)

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

  2. Dosimetry of the low fouence fast neutron beams for boron neutron capture therapy

    International Nuclear Information System (INIS)

    For the research of Boron Neutron Capture Therapy (BNCT), fast neutrons generated from the MC-50 cyclotron with maximum energy of 34.4 MeV in Korea Cancer Center Hospital were moderated by 70 cm paraffin and then the dose characteristics were investigated. Using these results, we hope to establish the protocol about dose measurement of epi-thermal neutron, to make a basis of dose characteristic of epi-thermal neutron emitted from nuclear reactor, and to find feasibility about accelerator-based BNCT. For measuring the absorbed dose and dose distribution of fast neutron beams, we used Unidos 10005 (PTW, Germany) electrometer and IC-17 (Far West, USA), IC-18, EIC-1 ion chambers manufactured by A-150 plastic and used IC-17M ion chamber manufactured by magnesium for gamma dose. There chambers were flushed with tissue equivalent gas and argon gas and then the flow rate was 5 cc per minute. Using Monte Carlo N-Particle (MCNP) code, transport program in mixed field with neutron, photon, electron, two dimensional dose and energy fluence distribution was calculated and, there results were compared with measured results. The absorbed dose of fast neutron beams was 6.47 x 10-3 cGy per 1 MU at the 4 cm depth of the water phantom, which is assumed to be effective depth for BNCT. The magnitude of gamma contamination intermingled with fast neutron beams was 65.2±0.9% at the same depth. In the dose distribution according to the depth or water, the neutron dose decreased linearly and the gamma dose decreased exponentially as the depth was deepened. The factor expressed energy level, D20/DI0, of the total dose was 0.718. Through the direct measurement using the two ion chambers, which is made different wall materials, and computer calculation of isodose distribution using MCNP simulation method, we have found the dose characteristics of low fluence fast neutron beams. If the power supply and the target material, which generate high voltage and current, will be developed and gamma

  3. Dosimetry and dose planning in boron neutron capture therapy : Monte Carlo studies

    Energy Technology Data Exchange (ETDEWEB)

    Koivunoro, H.

    2012-07-01

    Boron neutron capture therapy (BNCT) is a biologically targeted radiotherapy modality. So far, 249 cancer patients have received BNCT at the Finnish Research Reactor 1 (FiR 1) in Finland. The effectiveness and safety of radiotherapy are dependent on the radiation dose delivered to the tumor and healthy tissues, and on the accuracy of the doses. At FiR 1, patient dose calculations are performed with the Monte Carlo (MC) -based treatmentplanning system (TPS), Simulation Environment for Radiotherapy Applications (SERA). Initially, BNCT was applied to head and neck cancer, brain tumors, and malignant melanoma. To evaluate the applicability of the new target tumors for BNCT, calculation dosimetry studies are needed. So far, clinical BNCT has been performed with the neutrons from a nuclear reactor, while an accelerator based neutron sources applicable for hospital operation would be preferable. In this thesis, BNCT patient dose calculation practice in Finland was evaluated against reference calculations and experimental data in several cases. Calculations with two TPSs applied in clinical BNCT were compared. The suitability of the deuterium-deuterium (DD) and deuterium-tritium (D-T) fusion reaction-based compact neutron sources for BNCT were evaluated. In addition, feasibility of BNCT for noninvasive liver tumor treatments was examined. The deviation between SERA and the reference calculations was within 4% in the phantoms studied and in a brain cancer patient model elsewhere, except on the phantom or skin surface, for the boron, nitrogen, and photon dose components. These dose components produce 99% of the tumor dose and > 90% of the healthy tissue dose at points of relevance for treatment at the FiR 1 facility. The reduced voxel cell size ({<=} 0.5 cm) in the SERA edit mesh improved calculation accuracy on the surface. The erratic biased fastneutron run option in SERA led to significant underestimation (up to 30-60%) of the fastneutron dose, while more accurate fast

  4. Determination of boron in biological samples for the needs of neutron capture therapy

    International Nuclear Information System (INIS)

    Monitoring the actual concentration of 10B in a patient's blood is a prerequisite for determining the start and length of patient irradiation. The Prompt Gamma Ray Analysis (PGRA) method enables this nuclide to be determined rapidly and reliably within the region of 1 to 100 ppm. In this method, the characteristic line at 478 keV from the nuclear reaction 10B+n → 7Li+α+γ during sample exposure to thermal neutrons is used to determine boron. The facility which has been built up for this purpose comprises, in particular, a large-volume semiconductor detector for recording gamma rays emerging from the radiative neutron capture on the target

  5. Transport calculations in the influence of physical factors on depth-dose distributions in boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, T. (Musashi Inst. of Tech., Kawasaki, Kanagawa (Japan). Atomic Energy Research Lab.)

    1990-07-01

    Distributions of thermal neutron fluence and capture {gamma} ray absorbed dose rates were evaluated, taking into consideration various physical factors relevant to boron neutron capture therapy. The use of a larger neutron irradiation aperture was associated with an increase in thermal neutron fluence and capture {gamma} ray absorbed dose rates. Radiation leakage was more significant with smaller phantoms. Attenuation of thermal neutron fluence rates by {sup 10}B suggested that there was an optimal {sup 10}B concentration (<100 PPM) for a given tumour. Deuteration of water allowed better penetration of thermal neutrons with less capture {gamma} rays and is potentially applicable for the treatment of deep-seated brain tumours. (author).

  6. In-phantom dosimetry using the 13C(d,n)14N reaction for BNCT (boron neutron capture therapy)

    International Nuclear Information System (INIS)

    The use of the 13 C(d,n)14 N reaction at Ed =1.5 MeV for accelerator-based boron neutron capture therapy is investigated. The 13 C(d,n)14 N reaction presents the advantages of carbon as a target material and its large cross section. The deuteron beam was produced by a tandem accelerator at MIT's Laboratory for Accelerator Beam Applications. The resulting neutron spectra were evaluated in terms of RBE-dose rates at different depths inside a water-filled brain phantom using a heavy water moderator and lead reflector assembly. All results were simulated using the code MCNP. (author)

  7. 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.

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

    International Nuclear Information System (INIS)

    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

  9. Boron determination in biological samples - Intercomparison of three analytical methods to assist development of a treatment protocol for neoplastic diseases of the liver with Boron Neutron Capture Therapy

    OpenAIRE

    Schütz, Christian L.

    2012-01-01

    Die Bor-Neuroneneinfang-Therapie (engl.: Boron Neutron Capture Therapy, BNCT) ist eine indirekte Strahlentherapie, welche durch die gezielte Freisetzung von dicht ionisierender Strahlung Tumorzellen zerstört. Die freigesetzten Ionen sind Spaltfragmente einer Kernreaktion, bei welcher das Isotop 10B ein niederenergetisches (thermisches) Neutron einfängt. Das 10B wird durch ein spezielles Borpräparat in den Tumorzellen angereichert, welches selbst nicht radioaktiv ist. rnAn der Johannes Gutenbe...

  10. Intracellular boron localization and uptake in cell cultures using imaging secondary ion mass spectrometry (ion microscopy) for neutron capture therapy for cancer.

    Science.gov (United States)

    Bennett, B D; Zha, X; Gay, I; Morrison, G H

    1992-01-01

    Quantitative ion microscopy of freeze-fractured, freeze-dried cultured cells is a technique for single cell and subcellular elemental analysis. This review describes the technique and its usefulness in determining the uptake and subcellular distribution of the boron from boron neutron capture therapy drugs. PMID:1511239

  11. The relationship between boron neutron capture therapy (BNCT) and positron emission tomography (PET) for malignant brain tumors

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is a particle irradiation therapy that is theoretically available for selective radiation of tumor cells. Boronophenylalanine-positron emission tomography (18F-BPA-PET) was used in this study. Boron is used as a tracer compound for the neutron capture reaction and has been particularly useful for the recent noncraniotomy BNCT. In this report, we introduce this type of PET as a principal axis in BNCT and relationship with PET. We calculated the drug accumulation to the tumor before neutron irradiation to individualize the treatment. We decided the indication for BNCT on the basis of a PET study and are now expanding the indications to other systemic cancers, including head and neck, lung, and liver cancers. In addition, other irradiation modalities have developed a radiation plan on the basis of a PET study, and several studies attempted improving the results; however, the lesion is exposed to high radiation doses and appear as high accumulation on BPA-PET during BNCT. We determined the neutron exposure time from the dosage for normal tissue in the actual treatment, but the lesion/normal tissue ratio obtained from BPA-PET is for evaluating the tumor dose and following the treatment plan. We also found that a PET study was useful in the follow-up stage to aid in diagnosis of pathologic conditions such as increase in tumor volume, recurrence, or radiation necrosis and for patients who had already been treated for malignant brain tumor. (author)

  12. [Principles of therapy with fission neutrons and boron neutron capture therapy for radioresistant head-neck malignancies].

    Science.gov (United States)

    Clasen, B

    1990-08-01

    Neutron therapy has proven to be clinically useful in cases of advanced, slow-growing radioresistant head and neck carcinoma. Therapeutic effects might be based on direct DNA damaging and thus immediate cell-killing, on the generation of free oxygen radicals and, among others, on the fact that heavy particle radiation is said to be less dependent on the presence of oxygen than gamma rays, i.e. on a lower oxygen enhancement ratio (OER). The smaller difference in reaction between oxygenated and nonoxygenated cells could entail advantages as well as disadvantages, depending on the characteristics of the tumor cell population and of the normal tissue. It is therefore essential to select patients and tumours with an expectedly high therapeutic gain factor. Fission neutrons for tumour therapy: As evaluated by several in vitro and in vivo studies (11/13) the biological efficiency (RBE) of the RENT (Reactor Neutron Therapy) beam in Munich seems to be among the highest of all clinically used neutron beams. For a single dose range between 2 and 8 Gy the RBE for chronic radiation damage is relatively small (2). Consequently, patients with recurrent or metastatic carcinomas of the head and neck are treated with a single dose of 200-250 cGy after previous surgery and/or combined radiochemotherapy. The main limitation of fission neutrons is the small penetration depth. Possibilities of clinical implementation of boron neutron capture therapy (BNCT) in otorhinolaryngology: In near surface tumours it is possible to administer high doses of 10boron not selectively, i.e. no selective tumour-seeking compound is needed. Animal experiments with intratumoural injection of 10boron glycine have shown a strong effect on tumour growth delay (18).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2222692

  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

    Science.gov (United States)

    2009-01-01

    Boron neutron capture therapy (BNCT) is increasingly being used in the treatment of several aggressive cancers, including cerebral glioblastoma multiforme. The main requirement for this therapy is selective targeting of tumor cells by sufficient quantities of10B atoms required for their capture/irradiation with low-energy thermal neutrons. The low content of boron targeting species in glioblastoma multiforme accounts for the difficulty in selective targeting of this very malignant cerebral tumor by this radiation modality. In the present study, we have used for the first time boron nitride nanotubes as carriers of boron atoms to overcome this problem and enhance the selective targeting and ablative efficacy of BNCT for these tumors. Following their dispersion in aqueous solution by noncovalent coating with biocompatible poly-l-lysine solutions, boron nitride nanotubes were functionalized with a fluorescent probe (quantum dots) to enable their tracking and with folic acid as selective tumor targeting ligand. Initial in vitro studies have confirmed substantive and selective uptake of these nanovectors by glioblastoma multiforme cells, an observation which confirms their potential clinical application for BNCT therapy for these malignant cerebral tumors. PMID:20596476

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

    International Nuclear Information System (INIS)

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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)

  16. Boron concentrations in brain during boron neutron capture therapy: in vivo measurements from the Phase I trial EORTC 11961 using a gamma-ray telescope

    International Nuclear Information System (INIS)

    Purpose: Gamma-ray spectroscopic scans to measure boron concentrations in the irradiated volume were performed during treatment of 5 patients suffering from brain tumors with boron neutron capture therapy (BNCT). In BNCT, the dose that is meant to be targeted primarily to the tumor is the dose coming from the reaction 10B(n,α)7Li, which is determined by the boron concentration in tissue and the thermal neutron fluence rate. The boron distribution throughout the head of the patient during the treatment is therefore of major interest. The detection of the boron distribution during the irradiation was until now not possible. Methods and Materials: Five patients suffering from glioblastoma multiforme and treated with BNCT in a dose escalation study were administered the boron compound, boron sulfhydryl (BSH; Na2B12H11SH). Boron concentrations were reconstructed from measurements performed with the gamma-ray telescope which detects locally the specific gamma rays produced by neutron capture in 10B and 1H. Results: For all patients, at a 10B concentration in blood of 30 ppm, the boron concentration in nonoperated areas of the brain was very low, between 1 and 2.5 ppm. In the target volume, which included the area where the tumor had been removed and where remaining tumor cells have to be assumed, much higher boron concentrations were measured with large variations from one patient to another. Superficial tissue contained a higher concentration of 10B than the nonoperated areas of the brain, ranging between 8 and 15 ppm. Conclusions: The measured results correspond with previous tissue uptake studies, confirming that normal brain tissue hardly absorbs the boron compound BSH. Gamma-ray telescope measurements seem to be a promising method to provide information on the biodistribution of boron during therapy. Furthermore, it also opens the possibility of in vivo dosimetry

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

    International Nuclear Information System (INIS)

    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, 1H 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

  18. Design of an epi-thermal neutron flux intensity monitor with GaN wafer for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is a promising cancer therapy. Epi-thermal neutron (0.5 eV < En < 10 keV) flux intensity is one of the basic characteristics for modern BNCT. In this work, based on the 71Ga(n, γ)72Ga reaction, a new simple monitor with gallium nitride (GaN) wafer as activation material was designed by Monte Carlo simulations to precisely measure the absolute integral flux intensity of epi-thermal neutrons especially for practical BNCT. In the monitor, a GaN wafer was positioned in the center of a polyethylene sphere as neutron moderator covered with cadmium (Cd) layer as thermal neutron absorber outside. The simulation results and related analysis indicated that the epi-thermal neutron flux intensity could be precisely measured by the presently designed monitor. (author)

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

    Science.gov (United States)

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

    2015-07-01

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

  20. 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 and prediction of the dose for each pellet, beside the results of the measurements, calculations with the Monte Carlo code FLUKA are presented here. For the phantom, as well as for the liver tissue, the measured and calculated dose and flux values are in good agreement. Discussion Alanine......Introduction Boron Neutron Capture Therapy for liver malignancies is being investigated at the University of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and may...

  1. Design of a plate type fuel based - low power medical reactor for boron neutron capture therapy

    International Nuclear Information System (INIS)

    The interest in the boron neutron capture therapy (BNCT) has been renewed for cancer therapy with some indication of its potential efficacy in recent years. To solve the most important problem that thermal neutrons are attenuated rapidly in tissue due to absorption and scattering, thermal neutron beams are replaced by epithermal neutron beams. Thus, epithermal neutron beams are directed towards a patient's head, during their passage through tissue these neutrons rapidly lose energy by elastic scattering until they end up as thermal neutrons in target tumor volume. The thermal neutrons thus formed, are captured by the 10B atoms which become 11B atoms in the excited state for a very short time 10-12 sec. The 11B atoms then decay producing alpha particles, 7Li recoil nuclei and gamma rays. Tumor cells are killed selectively by the energetic alpha particles and 7Li fission products. We propose a 300kW slab type reactor core having thin and large surface areas so that most of the neutrons emerging from the faces and entering moderator region are fission spectrum neutrons to acquire high intense epithermal neutron beam with high quality. All faces of the slab core, East-West region and North-South region, were considered for epithermal neutron beam collimators. Plate-type U3Si2-Al dispersion fuel having high uranium density is very compatible with composing of a slab type core. The reactor core is loaded with 3.89kg U235 and has the dimension of about 23.46cm width, 31.28cm length and 64.8cm height, with 216 locations to place 204 fuel elements, eight control plates and four safety plates. The general-purpose MCNP 4B code was used to carry out the neutron and photon transport computations. Both keff criticality and fixed source problems were computed. We could reduce at least 7 times long computer time (105 to 140 h in a run) needed to initiate enough neutrons in a run ( 6000 to 8000 cycles in a run with 3000 neutrons per cycle) using the PVM (Parallel Virtual

  2. Gadolinium as a Neutron Capture Therapy Agent

    Science.gov (United States)

    Shih, Jing-Luen Allen

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

  3. Nine-year interval recurrence after treatment of boron neutron capture therapy in a patient with glioblastoma: A case report

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) has been reported to be effective in the patients with glioblastoma multiforme (GBM). Median survival time (MST) of GBM patients treated with BNCT is approximately two years. GBM patients surviving 2 or 3 years are considered long-term survivors. In general, most recurrences are local and dissemination is rare. We report an unusual patient with three recurrences; the first and the second recurrences were local, and the third recurrence was dissemination nine years after BNCT. - Highlights: • A patients with glioblastoma mutliforme could be alive more than 9 years after BNCT. • BNCT may be effective for the local control of GBM. • The following TMZ and conventional radiation may be effective for prevention of CSF dissemination

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

    International Nuclear Information System (INIS)

    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

  5. Correlation between radiation dose and histopathological findings in patients with gliblastoma treated with boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    The purpose of this study was to clarify the correlation between the radiation dose and histopathological findings in patients with glioblastoma multiforme (GBM) treated with boron neutron capture therapy (BNCT). Histopathological studies were performed on specimens from 8 patients, 3 had undergone salvage surgery and 5 were autopsied. For histopathological cure of GBM at the primary site, the optimal minimal dose to the gross tumor volume (GTV) and the clinical target volume (CTV) were 68 Gy(w) and 44 Gy(w), respectively. - Highlights: • It is very important to determine the curable BNCT radiation dose on histopathological aspect in BNCT. • Of 23 patients with GBM treated with BNCT, autopsy was performed in 5, salvage surgery in 3, and histopathological study in 8. • To achieve the histopathological cure of GBM at the primary site, the optimal minimal dose to the GTV and CTV was 68 Gy(w) and 44 Gy(w), respectively

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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.

  8. P13.09ADVANCES IN CLINICAL APPLICATION OF BORON NEUTRON CAPTURE THERAPY (BNCT) IN GLIOBLASTOMA

    OpenAIRE

    Detta, A.; Cruickshank, G.C.; Green, S.; Lockyer, N.P.; Ngoga, D.; Ghani, Z.; Phoenix, B

    2014-01-01

    BNCT is a biologically targeted form of enhanced cellular radiotherapy where preferential accumulation of boron in the cancerous as opposed to adjacent normal cells is able to interact with incident neutrons to cause irreversible alpha particle DNA damage. The key to the implementation of this potentially powerful and selective therapy is the delivery of at least 30ppm 10B within the tumour tissue while minimising superfluous 10B in healthy tissue. It is thus an elegant technique for treating...

  9. Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent

    International Nuclear Information System (INIS)

    Cetuximab (IMC-C225) is a monoclonal antibody directed against both the wild-type and mutant vIII isoform of the epidermal growth factor receptor (EGFR). The purpose of the present study was to evaluate the monoclonal antibody (MoAb), cetuximab, as a boron delivery agent for neutron capture therapy (NCT) of brain tumors. Twenty-four hours following intratumoral (i.t.) administration of boronated cetuximab (C225-G5-B1100), the mean boron concentration in rats bearing either F98EGFR or F98WT gliomas were 92.3±23.3 μg/g and 36.5±18.8 μg/g, respectively. In contrast, the uptake of boronated dendrimer (G5-B1000) was 6.7±3.6 μg/g. Based on its favorable in vivo uptake, C225-G5-B1100 was evaluated as a delivery agent for BNCT in F98EGFR glioma bearing rats. The mean survival time (MST) of rats that received C225-G5-B1100, administered by convection enhanced delivery (CED), was 45±3 d compared to 25±3 d for untreated control animals. A further enhancement in MST to >59 d was obtained by administering C225-G5-B1100 in combination with i.v. boronophenylalanine (BPA). These data are the first to demonstrate the efficacy of a boronated MoAb for BNCT of an intracerebral (i.c.) glioma and are paradigmatic for future studies using a combination of boronated MoAbs and low molecular weight delivery agents

  10. Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent

    Energy Technology Data Exchange (ETDEWEB)

    Barth, Rolf F. E-mail: barth.1@osu.edu; Wu Gong; Yang Weilian; Binns, Peter J.; Riley, Kent J.; Patel, Hemant; Coderre, Jeffrey A.; Tjarks, Werner; Bandyopadhyaya, A.K.; Thirumamagal, B.T.S.; Ciesielski, Michael J.; Fenstermaker, Robert A

    2004-11-01

    Cetuximab (IMC-C225) is a monoclonal antibody directed against both the wild-type and mutant vIII isoform of the epidermal growth factor receptor (EGFR). The purpose of the present study was to evaluate the monoclonal antibody (MoAb), cetuximab, as a boron delivery agent for neutron capture therapy (NCT) of brain tumors. Twenty-four hours following intratumoral (i.t.) administration of boronated cetuximab (C225-G5-B{sub 1100}), the mean boron concentration in rats bearing either F98{sub EGFR} or F98{sub WT} gliomas were 92.3{+-}23.3 {mu}g/g and 36.5{+-}18.8 {mu}g/g, respectively. In contrast, the uptake of boronated dendrimer (G5-B{sub 1000}) was 6.7{+-}3.6 {mu}g/g. Based on its favorable in vivo uptake, C225-G5-B{sub 1100} was evaluated as a delivery agent for BNCT in F98{sub EGFR} glioma bearing rats. The mean survival time (MST) of rats that received C225-G5-B{sub 1100}, administered by convection enhanced delivery (CED), was 45{+-}3 d compared to 25{+-}3 d for untreated control animals. A further enhancement in MST to >59 d was obtained by administering C225-G5-B{sub 1100} in combination with i.v. boronophenylalanine (BPA). These data are the first to demonstrate the efficacy of a boronated MoAb for BNCT of an intracerebral (i.c.) glioma and are paradigmatic for future studies using a combination of boronated MoAbs and low molecular weight delivery agents.

  11. 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.

  12. P13.09ADVANCES IN CLINICAL APPLICATION OF BORON NEUTRON CAPTURE THERAPY (BNCT) IN GLIOBLASTOMA

    Science.gov (United States)

    Detta, A.; Cruickshank, G.C.; Green, S.; Lockyer, N.P.; Ngoga, D.; Ghani, Z.; Phoenix, B.

    2014-01-01

    BNCT is a biologically targeted form of enhanced cellular radiotherapy where preferential accumulation of boron in the cancerous as opposed to adjacent normal cells is able to interact with incident neutrons to cause irreversible alpha particle DNA damage. The key to the implementation of this potentially powerful and selective therapy is the delivery of at least 30ppm 10B within the tumour tissue while minimising superfluous 10B in healthy tissue. It is thus an elegant technique for treating infiltrating tumours such as diffuse gliomas. In order to assess its clinical potential we carried out a pharmacokinetic study in glioblastoma patients where we sought to determine the optimal route of delivering a new formulation of the boronated drug (p-boronophenylalanine, BPA), its pharmacokinetic behaviour, toxicity profile, and cellular uptake. Using a number of analytical techniques, including inductively-coupled plasma mass spectrometry, secondary ion mass spectrometry (SIMS) and immunohistochemistry (IHC), boron was measured at various times in blood, urine, cerebrospinal fluid, extracellular fluid (ECF), and tumour-related solid tissue spanning 0.5 h pre- and up to 48 h post-BPA infusion in newly-diagnosed patients (n = 10). Blood was sampled through a central catheter whilst the ECF was sampled by parenchymal microdialysis catheters, placed remotely from the tumour site. Urine was collected over the same time period. Tumour and brain-around tumour (BAT) tissue was sampled stereotactically at 2.5 h and 3.5 h post-infusion. IHC expression levels of the BPA transporter molecule, L-amino acid transporter 1 (LAT-1), were recorded as % LAT-1 positive cells, and cellular boron levels were estimated as spatially resolved pixels in normalised-to-C+ isotopic SIMS images of the biopsies. There were no toxicity-related issues with this new formulation of BPA given at 375 mg/kg as a 2 h intravenous or intracarotid infusion with or without pre-infusion mannitol-induced BBB

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

    International Nuclear Information System (INIS)

    This reaction can be applied to the therapy and diagnosis about the tumor simultaneously. After the compound labeled with the boron is accumulated at the tumor site, the alpha particle induced by the reaction between the thermal neutron and the boron induces tumor cell death. Also, the 478 keV prompt gamma ray is emitted from the same reaction point. If this single prompt photon is detected by single photon emission computed tomography (SPECT), the tomographic image of the therapy region can be monitored during the radiation treatment. However, in order to confirm the therapy region using the image during the treatment, the image needs to be provided promptly. Due to a relatively long acquisition time required to get SPECT images, both reduced number of projections and the fast image reconstruction schemes are needed to provide the images during radiation treatment. The computation time for image reconstruction using the GPU with the modified OSEM algorithm was measured and compared with the computation time using CPU. Through the results, we confirmed the feasibility of the image reconstruction for prompt gamma ray image using GPU for the BNCT. In the further study, the development of the algorithm for faster reconstruction of the prompt gamma ray image during the BNCT using the GPU computation will be conducted. Also, the analysis of the target to background level about the reconstructed image will be performed using the extracted image profile

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

    Science.gov (United States)

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

    2011-02-01

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

  15. Summary of dose plan system for boron neutron capture therapy 'SERA' and it's application at Kyoto University Reactor (KUR)

    International Nuclear Information System (INIS)

    It is difficult for epithermal neutron irradiation to measure doses of thermal and fast neutron at near the surface of body in boron neutron capture therapy (BNCT). Dose plan system for the BNCT, 'SERA' (Simulation Environment for Radiotherapy Applications) was developed by the groups of INEEL (Idaho National Engineering and Environment Laboratory) and MSU (Montana State University) in USA. The SERA system consists of seven modules in which contain image data of CT or MRI, three dimensional image data, two or three dimensional calculation, Monte Carlo simulation calculation, plan of irradiation conditions including boron concentration, one dimensional dose distribution and dose-volume histogram, and two dimensional dose distribution each. The BNCT using epithermal neutron irradiation and the SERA system was carried out to eight patients of tumor, six persons of oral tumor and two persons of brain tumor, in the KUR during Dec. 2001 - Oct. 2002. Thermal neutron flux, epithermal neutron flux and gamma ray doses are measured by phantom experiments. The calculated results of the SERA system give good agreement with the values obtained by the phantom experiments, within accuracy of 10%. (M. Suetake)

  16. Synthesis of conjugates of polyhedral boron compounds with tumor-seeking molecules for neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bregadze, V., E-mail: bre@ineos.ac.ru [A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov Str. 28, Moscow 119991 (Russian Federation); Semioshkin, A.; Sivaev, I. [A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov Str. 28, Moscow 119991 (Russian Federation)

    2011-12-15

    Recent achievements in design and synthesis of boronated acids, amino acids, glycerols as well as conjugates of polyhedral boron hydrides (ortho-carborane, closo-dodecaborate and cobalt bis(dicarbollide)) with natural porphyrins, carbohydrates and nucleosides are described.

  17. 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

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

    International Nuclear Information System (INIS)

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

  19. Neutron capture therapy at Brookhaven National Laboratory

    International Nuclear Information System (INIS)

    Application of the 10B(n,α)7Li 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

  20. Dose determination using alanine detectors in a mixed neutron and gamma field for boron neutron capture therapy of liver malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, Tobias (Inst. for Nuclear Chemistry, Univ. of Mainz, Mainz (Germany); Dept. of Pharmacy and Toxicology, Univ. of Mainz, Mainz (Germany)), e-mail: schmito@uni-mainz.de; Blaickner, Matthias (AIT Austrian Inst. of Technology GmbH, Vienna (Austria)); Ziegner, Markus (AIT Austrian Inst. of Technology GmbH, Vienna (Austria); TU Wien, Vienna Univ. of Technology, Vienna (Austria)) (and others)

    2011-08-15

    Boron Neutron Capture Therapy for liver malignancies is being investigated at the Univ. of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and may be suitable for measurements in mixed neutron and gamma fields. Material and methods. Two experiments have been carried out in the thermal column of the TRIGA Mark II reactor at the Univ. of Mainz. Alanine dosimeters have been irradiated in a phantom and in liver tissue. Results. For the interpretation and prediction of the dose for each pellet, beside the results of the measurements, calculations with the Monte Carlo code FLUKA are presented here. For the phantom, as well as for the liver tissue, the measured and calculated dose and flux values are in good agreement. Discussion. Alanine dosimeters, 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

  1. Dose determination using alanine detectors in a mixed neutron and gamma field for boron neutron capture therapy of liver malignancies

    International Nuclear Information System (INIS)

    Boron Neutron Capture Therapy for liver malignancies is being investigated at the Univ. of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and may be suitable for measurements in mixed neutron and gamma fields. Material and methods. Two experiments have been carried out in the thermal column of the TRIGA Mark II reactor at the Univ. of Mainz. Alanine dosimeters have been irradiated in a phantom and in liver tissue. Results. For the interpretation and prediction of the dose for each pellet, beside the results of the measurements, calculations with the Monte Carlo code FLUKA are presented here. For the phantom, as well as for the liver tissue, the measured and calculated dose and flux values are in good agreement. Discussion. Alanine dosimeters, 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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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

  5. The boron neutron capture therapy facility of the ETRR-2: a promising opportunity for cancer research and treatment

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is a binary modality that can selectively irradiate tumor tissue using drugs containing 10B that are capable of preferntially accumulating in the tumor, which is then irradiated with thermal neutrins. This casuses the 10B nucleus to split, releasing an alpha particle and a lithium nucleus. These products are very damaging to cells but have ranges of the order of cell diameters. The technique is minly used for the treatment of Glioblastoma, a highly malignant tumor whose treatment is not statisfactory using conventional techniques. Other types of cancer, like melanoma, are also considered. Since early nineties, the area of BNCT is witnessing active developments in the USA, Japan, and Europe. the Egyptian second experimental and training research reactor (ETRR-2) is a pool-type MPR. It has four neutron beam and a thermal column as the main experimental devices. One of the main reactor facilities is the BNCT unit. The paper highlights the basics of the BNCT, its development, and status around the world. A brief description of the reactor, the BNCt uint as well as the preliminary analysis done for the facility is presented. The BNCT offers a unique opportunity for coordinated efforts by the arab nuclear organizations and medical institutions similar to the on going efforts at Petten, the netherlands

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

    International Nuclear Information System (INIS)

    Purpose: To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. Methods and Materials: The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The 1B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumors and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D05 and D95, were adopted as the representative dose for the maximum and minimum dose, respectively. Results: When the D05 to the normal ipsilateral lung was 5 Gy-Eq, the D95 and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D05 and D95 doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. Conclusions: From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses

  7. Gamma/neutron dose evaluation using Fricke gel and alanine gel dosimeters to be applied in boron neutron capture therapy

    International Nuclear Information System (INIS)

    Full text: Radiosurgery is a non-invasive surgery carried out by means of directed beams of ionizing radiation. This procedure was developed since there are many diseases for which conventional surgical treatment can not be applied, due to difficult or vital structures being damaged. Neutron radiation from nuclear reactors is used in a kind of radiosurgery called Boron Neutron Capture Therapy (BNCT) for the treatment of brain tumours which depends on the interaction of slow neutrons with 10B isotope injected in the tumour to produce alpha particles. Gel Dosimetry allows three-dimensional (3D) measurement of absorbed dose in tissueequivalent dosimeter phantoms. The measure technique is based on the transformation of ferrous ions (Fe2+) and ferric ions (Fe3+). The ferric ions concentration can be measured by spectrophotometry technique comparing the two wavelengths, 457 nm band that corresponds to ferrous ions concentration and 588 nm band that corresponds to ferric ions concentration. This work aims to study the gamma/neutron reactor dose relationship to be applied in BNCT using gel dosimeters. The Fricke Xylenol Gel (FXG) and Alanine Gel (AG) gel solutions produced at IPEN using gelatine 300 bloom were mixed with Na2B4O7 salt containing 19,9% of 10B isotope. This solutions were used to evaluate thermal and epithermal neutrons and gamma doses at an irradiation cell on BH3 of the IEA-R1 research reactor of IPEN

  8. 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 ...

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

    Science.gov (United States)

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

    2015-07-15

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

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

    International Nuclear Information System (INIS)

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

  11. 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.

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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 10B to malignant tumor tissue. In this study, we focused on a tumor-targeting 10B delivery system (BDS) for BNCT that uses transferrin-conjugated polyethylene-glycol liposome encapsulating BSH (TF-PEG liposome-BSH) and compared 10B uptake of the tumor among BSH, PEG liposome-BSH and TF-PEG liposome-BSH. In vitro, we analyzed 10B concentration of the cultured human U87Δ glioma cells incubated in medium containing 20 μg 10B/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 10B/kg) intravenously. We analyzed 10B 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 10B concentration in blood and normal tissue while it maintained high 10B concentration in tumor tissue for a couple of days. This showed the TF-PEG liposome-BSH caused the selective delivery of high concentration of 10B to malignant tumor tissue. The TF-PEG liposome-BSH is more potent BDS for BNCT to obtain absolute high 10B concentration and good contrast between tumor and normal tissue than BSH and PEG liposome-BSH. (author)

  15. Intraoperative boron neutron capture therapy for malignant gliomas. First clinical results of Tsukuba phase I/II trial using JAERI mixed thermal-epithermal beam

    International Nuclear Information System (INIS)

    Since October 1999, a clinical trial of intraoperative boron neutron capture therapy (IOBNCT) is in progress at JRR-4 (Japan Research Reactor-4) in Japan Atomic Energy Research Institute (JAERI) using mixed thermal-epithermal beam (thermal neutron beam I: TNB-I). Compared to pure thermal beam (thermal neutron beam II: TNB-II), TNB-I has an improved neutron delivery into the deep region than TNB-II. The clinical protocol and the preliminary results will be discussed. (author)

  16. Medical set-up of boron neutron capture therapy (BNCT) for malignant glioma at the Japan research reactor (JRR)-4

    International Nuclear Information System (INIS)

    The University of Tsukuba project for boron neutron capture therapy (BNCT) was initiated at the Japan Atomic Energy Research Institute (JAERI) in 1992. The clinical study for BNCT began at the Japan Research Reactor (JRR)-2 of the JAERI in November 1995. By the end of 1998, a new medical irradiation facility had been installed in JRR-4 of that included a new medical treatment room and patient-monitoring area adjacent to the irradiation room. The medical treatment room was built to reflect a hospital-type operation room that includes an operating table with a carbon head frame, anesthesia apparatus with several cardiopulmonary monitors, etc. Following craniotomy in the treatment room, a patient under anesthesia is transported into the irradiation room for BNCT. The boron concentration in tissue is measured with prompt gamma ray analysis (PGA) and simultaneously by inductively coupled plasma atomic emission spectroscopy (ICP-AES) methods. For the immediate pre- and post-BNCT care, a collaborating neurosurgical department of the University of Tsukuba was prepared in the vicinity of the JAERI. The long term follow-up is done at the University of Tsukuba Hospital. Epithermal neutron beam also became available at the new JRR-4. By changing the thickness and/or the configuration of heavy water, a cadmium plate, and a graphite reflector, the JRR-4 provides a variety of neutron beams, including three typical beams (Epithermal mode and Thermal modes I and II). Intraoperative BNCT using the thermal beam is planned to study at the beginning of the clinical trial. The ongoing development of the JAERI Computational Dosimetry System (JCDS) and radiobiological studies have focused in the application of the epithermal beam for BNCT. After obtaining these basic data, we are planning to use the epithermal beam for intraoperative BNCT. (author)

  17. Biomedical irradiation system for boron neutron capture therapy at the Kyoto University reactor

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    BNCT is an experimental radiotherapeutic modality that uses the capacity of the isotope 10B to capture thermal neutrons leading to the production of 4He and 7Li, 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 10B) + neutrons; 2) BOPP (10 ppm 10B) + 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= 7.5 109 n/cm2 sec) or with 60Co (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 10BPA or 10BOPP 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)

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

    International Nuclear Information System (INIS)

    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

  20. 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.

  1. Proton magnetic resonance spectroscopy of a boron neutron capture therapy 10B-carrier, L-p-boronophenylalanine-fructose complex

    Energy Technology Data Exchange (ETDEWEB)

    Timonen, M.

    2010-07-01

    Boron neutron capture therapy (BNCT) is a radiotherapy that has mainly been used to treat malignant brain tumours, melanomas, and head and neck cancer. In BNCT, the patient receives an intravenous infusion of a 10B-carrier, which accumulates in the tumour area. The tumour is irradiated with epithermal or thermal neutrons, which result in a boron neutron capture reaction that generates heavy particles to damage tumour cells. In Finland, boronophenylalanine fructose (BPA-F) is used as the 10B-carrier. Currently, the drifting of boron from blood to tumour as well as the spatial and temporal accumulation of boron in the brain, are not precisely known. Proton magnetic resonance spectroscopy (1H MRS) could be used for selective BPA-F detection and quantification as aromatic protons of BPA resonate in the spectrum region, which is clear of brain metabolite signals. This study, which included both phantom and in vivo studies, examined the validity of 1H MRS as a tool for BPA detection. In the phantom study, BPA quantification was studied at 1.5 and 3.0 T with single voxel 1H MRS, and at 1.5 T with magnetic resonance imaging (MRSI). The detection limit of BPA was determined in phantom conditions at 1.5 T and 3.0 T using single voxel 1H MRS, and at 1.5 T using MRSI. In phantom conditions, BPA quantification accuracy of +- 5% and +- 15% were achieved with single voxel MRS using external or internal (internal water signal) concentration references, respectively. For MRSI, a quantification accuracy of <5% was obtained using an internal concentration reference (creatine). The detection limits of BPA in phantom conditions for the PRESS sequence were 0.7 (3.0 T) and 1.4 mM (1.5 T) mM with 20 x 20 single voxel MRS, and 1.0 mM with acquisition-weighted MRSI, respectively. In the in vivo study, an MRSI or single voxel MRS or both was performed for ten patients (patients 1-10) on the day of BNCT. Three patients had glioblastoma multiforme (GBM), and five patients had a recurrent or

  2. Preliminary study of MAGAT polymer gel dosimetry for boron-neutron capture therapy

    International Nuclear Information System (INIS)

    MAGAT gel dosimeter with boron is irradiated in Heavy Water Neutron Irradiation Facility (HWNIF) of Kyoto University Research Reactor (KUR). The cylindrical gel phantoms are exposed to neutron beams of three different energy spectra (thermal neutron rich, epithermal and fast neutron rich and the mixed modes) in air. Preliminary results corresponding to depth-dose responses are obtained as the transverse relaxation rate (R2=1/T2) from magnetic resonance imaging data. As the results MAGAT gel dosimeter has the higher sensitivity on thermal neutron than on epi-thermal and fast neutron, and the gel with boron showed an enhancement and a change in the depth-R2 response explicitly. From these results, it is suggested that MAGAT gel dosimeter can be an effective tool in BNCT dosimetry

  3. Preliminary study of MAGAT polymer gel dosimetry for boron-neutron capture therapy

    Science.gov (United States)

    Hayashi, Shin-ichiro; Sakurai, Yoshinori; Uchida, Ryohei; Suzuki, Minoru; Usui, Shuji; Tominaga, Takahiro

    2015-01-01

    MAGAT gel dosimeter with boron is irradiated in Heavy Water Neutron Irradiation Facility (HWNIF) of Kyoto University Research Reactor (KUR). The cylindrical gel phantoms are exposed to neutron beams of three different energy spectra (thermal neutron rich, epithermal and fast neutron rich and the mixed modes) in air. Preliminary results corresponding to depth-dose responses are obtained as the transverse relaxation rate (R2=1/T2) from magnetic resonance imaging data. As the results MAGAT gel dosimeter has the higher sensitivity on thermal neutron than on epi-thermal and fast neutron, and the gel with boron showed an enhancement and a change in the depth-R2 response explicitly. From these results, it is suggested that MAGAT gel dosimeter can be an effective tool in BNCT dosimetry.

  4. Neutron capture therapy of murine melanoma on new boron carriers with use of capillary neutron optics

    Science.gov (United States)

    Borisov, G. I.; Naidenov, M. G.; Koldaeva, E. Y.; Petrov, S. A.; Zhizhin, K. Y.; Kuznettsov, N. T.; Brattsev, V. A.; Grigorieva, E. Y.

    2005-07-01

    The Boron-10 NCT is one of the most perspective methods of human anticancer treatment. The introduction of this efficient method into medical practice makes possible more selective and precise destruction of tumour cells without any damage of normal tissues. The basis of NCT method is destructive effect of products of nuclear reaction 10B(n,α,γ)7Li. This reaction produces particles-helium nuclei (alpha-particles) and lithium nuclei-with too high linear energetic loss in animal tissues and poor integrated sweep (to 14 μm) what is comparable with single cell diameter. Actual use of BNCT for treatment of human malignant tumours is dependent on resolution of various and complex scientific and technical problems. Namely: the development of novel boron preparations selectively carrying 10B into cancer cells, providing optimal concentration and microdistribution of 10B in these and remaining there during all necessary irradiation time; formation of therapeutic neutron fluxes of needed power, spectrum and intensity; provision of adequate planning and monitoring methods for current 10B-NCT making possible to evaluate a boron concentration in animal tissues in real time, to see macro- and microdistribution of the same, allowing precise microdosimetry; optimization of irradiation regimens and of drug administration schedules conformably to concrete neutron flux in different objects.

  5. Recent advances in neutron capture therapy (NCT)

    Energy Technology Data Exchange (ETDEWEB)

    Fairchild, R.G.

    1985-01-01

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

  6. Microdosimetric spectra of the THOR neutron beam for boron neutron capture therapy

    International Nuclear Information System (INIS)

    A primary objective of the BNCT project in Taiwan, involving THOR (Tsing Hua Open Pool Reactor), was to examine the potential treatment of hepatoma. To characterise the epithermal neutron beam in THOR, the microdosimetry distributions in lineal energy were determined using paired tissue-equivalent proportional counters with and without boron microfoils. Microdosimetry results were obtained in free-air and at various depths in a PMMA phantom near the exit of the beam port. A biological weighting function, dependent on lineal energy, was used to estimate the relative biological effectiveness of the beam. An effective RBE of 2.7 was found at several depths in the phantom. (author)

  7. Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

    Science.gov (United States)

    Gao, Zhenyu; Horiguchi, Yukichi; Nakai, Kei; Matsumura, Akira; Suzuki, Minoru; Ono, Koji; Nagasaki, Yukio

    2016-10-01

    A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance. PMID:27467416

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

    International Nuclear Information System (INIS)

    The goals of the present study were two-fold. First, to determine the biodistribution of three carboranyl-porphyrins, designated H2DCP, H2TCP and H2TBP 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 H2DCP and H2TCP, respectively, and were 103 and 62 μg/g for H2TCP and H2TBP, 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 2TCP and H2TBP 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 H2TCP or H2TBP. 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 H2TCP by CED, followed by BNCT, had a MST of 35±4 days and animals received H2TBP had a MST of 44±10 days. Further studies were carried out using H2TBP 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)

  9. 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. PMID:24559940

  10. Epithermal neutron beam adoption for lung and pancreatic cancer treatment by boron neutron capture therapy

    International Nuclear Information System (INIS)

    The depth-dose distributions were evaluated for possible treatment of both lung and pancreatic cancers using an epithermal neutron beam. The Monte Carlo Neutron Photon (MCNP) calculations showed that physical dose in tumors were 6 and 7 Gy/h, respectively, for lung and pancreas, attaining an epithermal neutron flux of 5 x 108 ncm-2s-1. The boron concentrations were assumed at 100 ppm and 30 ppm, respectively, for lung and pancreas tumors and normal tissues contains 1/10 tumor concentrations. The dose ratios of tumor to normal tissue were 2.5 and 2.4, respectively, for lung and pancreas. The dose evaluation suggests that BNCT using an epithermal neutron beam could be applied for both lung and pancreatic cancer treatment. (author)

  11. Azanonaborane-containing sugars as possible boron carriers for neutron capture therapy

    International Nuclear Information System (INIS)

    A convenient synthetic route to N-glycosyl-azanonaborane derived from B8N cluster [H2N)CH2)4H2NB8H11NH(CH2)4NH2] and acetobromo-α-D-glucose and acetobromo-α-D-galactose followed by deacetylation is presented where the pure product is easily isolated. In a one step process, treatment of B8N cluster with D-ribose in methanol in the presence of a catalytic amount of glacial acetic acid gave N,N'-diglycosylamines in high yield. The in vitro toxicity studies using B16 melanoma cells showed that N-glycosyl-azanonaborane clusters are not toxic even at boron concentrations of 3 mM. (author)

  12. First clinical trial of boron neutron capture therapy for thyroid cancer

    International Nuclear Information System (INIS)

    We treated a patient with extrathyroidal papillary carcinoma who could not undergo surgery because of direct tracheal invasion. We confirmed the BPA accumulating capacity of the tumor by 18F-BPA PET prior to BNCT. The tumor/normal tissue boron concentration ratio (T/N ratio) was 2.9. We decided to carry out curative doses of BNCT twice because of the tumor's huge mass. In October 2003, the first BNCT was carried out. There has been gradual regression in the tumor for 1.5 years up to present. At present, no new lesions have appeared. Although papillary thyroid carcinoma is a typical radio-resistant tumor, BNCT had significant effects without inducing a skin reaction. (author)

  13. Preparation of a radioactive boron compound (B-I-131-lipiodol) for neutron capture therapy of hepatoma

    International Nuclear Information System (INIS)

    In our research, a radioactive boron compound, B-I-131-lipiodol, that can be selectively retained in hepatoma cells was prepared. Combining the effect of α particles produced by boron neutron capture reaction with the β particles released by radionuclides in the radioactive boron compounds will produce a synergistic killing effect on cancer cells. Human hepatoma HepG2 cell cultures were used to examine the stability and the intracellular distribution of the radioactive boron drug. Microscopes were used to examine the interaction and retention of B-I-131-lipiodol globules in the individual hepatoma cell. Moreover, ICP-AES and NaI scintillation counter were performed to determine boron concentrations and I-131 radioactivity, respectively. Results showed that B-I-131-lipiodol with a boron concentration and a specific radioactivity ranged from 500-2000 ppm and 0.05-10 mCi/mL respectively was stably retained in serum. The radiochemical purity of B-I-131-lipiodol was 98%. After supplement with a medium containing B-I-131-lipiodol, the HepG2 cells had intracellular B-I-131-lipiodol globules in the cytoplasm as seen by inverted light microscope, the I-131 and boron can be stably retained in HepG2 cells. (author)

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

    International Nuclear Information System (INIS)

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

  15. 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, T.D. Jr.

    1995-05-01

    The non-surgical brain cancer treatment modality, Boron Neutron Capture Therapy (BNCT), requires the use of an epithermal neutron beam. This purpose of this thesis was to design an epithermal neutron beam at the University of Virginia Research Reactor (UVAR) suitable for BNCT applications. A suitable epithermal neutron beam for BNCT must have minimal fast neutron and gamma radiation contamination, and yet retain an appreciable intensity. The low power of the UVAR core makes reaching a balance between beam quality and intensity a very challenging design endeavor. The MCNP monte carlo neutron transport code was used to develop an equivalent core radiation source, and to perform the subsequent neutron transport calculations necessary for beam model analysis and development. The code accuracy was validated by benchmarking output against experimental criticality measurements. An epithermal beam was designed for the UVAR, with performance characteristics comparable to beams at facilities with cores of higher power. The epithermal neutron intensity of this beam is 2.2 {times} 10{sup 8} n/cm{sup 2} {center_dot} s. The fast neutron and gamma radiation KERMA factors are 10 {times} 10{sup {minus}11}cGy{center_dot}cm{sup 2}/n{sub epi} and 20 {times} 10{sup {minus}11} cGy{center_dot}cm{sup 2}/n{sub epi}, respectively, and the current-to-flux ratio is 0.85. This thesis has shown that the UVAR has the capability to provide BNCT treatments, however the performance characteristics of the final beam of this study were limited by the low core power.

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

    International Nuclear Information System (INIS)

    The Monte Carlo stochastic simulation technique has traditionally been the only well-recognized method for computing three-dimensional radiation dose distributions in connection with boron neutron capture therapy (BNCT) research. A deterministic approach to this problem would offer some advantages over the Monte Carlo method. This paper describes an application of a deterministic method to analytically simulate BNCT treatment of a canine head phantom using the epithermal neutron beam at the Brookhaven medical research reactor (BMRR). Calculations were performed with the TORT code from Oak Ridge National Laboratory (ORNL), an implementation of the discrete ordinates, or Sn method. Calculations were from first principles and used no empirical correction factors. The phantom surface was modeled by flat facets of approximately 1 cm2. The phantom interior was homogeneous. Energy-dependent neutron and photon scalar fluxes were calculated on a 32x16x22 mesh structure with 96 discrete directions in angular phase space. The calculation took 670 min on an Apollo DN10000 workstation. The results were subsequently integrated over energy to obtain full three-dimensional dose distributions. Isodose contours and depth-dose curves were plotted for several separate dose components of interest. Phantom measurements were made by measuring neutron activation (and therefore neutron flux) as a function of depth in copper--gold alloy wires that were inserted through catheters placed in holes drilled in the phantom. Measurements agreed with calculations to within about 15%. The calculations took about an order of magnitude longer than comparable Monte Carlo calculations but provided various conveniences, as well as a useful check

  17. Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) is a selective radiotherapy, being effective for the treatment of even advanced malignancies in head and neck regions as well as brain tumors and skin melanomas. To clarify the role of p53 gene, the effect of BNCT on oral squamous cell carcinoma (SCC) cells showing either wild- (SAS/neo) or mutant-type (SAS/mp53) p53 was examined. Cells were exposed to neutron beams in the presence of boronophenylalanine (BPA) at Kyoto University Research Reactor. Treated cells were monitored for modulations in colony formation, proliferation, cell cycle, and expression of cell cycle-associated proteins. When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells. Cell cycle arrest at the G1 checkpoint was observed in SAS/neo, but not in SAS/mp53. Apoptotic cells increased from 6 h after BNCT in SAS/neo and 48 h in SAS/mp53 cells. The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines. These results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance. At a physical dose affecting the cell cycle, BNCT inhibits oral SCC cells in p53-dependent and -independent manners

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

    Energy Technology Data Exchange (ETDEWEB)

    Altieri, S.; Bortolussi, S.; Stella, S.; Bruschi, P.; Gadan, M.A. [University of Pavia (Italy); INFN - National Institute for Nuclear Physics, of Pavia (Italy)

    2008-10-29

    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,{alpha}) 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

  19. 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)

    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.)

  20. Boron Neutron Capture Therapy (BNCT) Breaks New Ground for Cancer Radiotherapy

    International Nuclear Information System (INIS)

    10B nucleus captures a slow speed neutron (thermal neutron), and imediately the nucleus slits into 4He nucleus and 7Li nucleus, These have very short track rangs that don't exceed general cell diameter. So, if 10B-compound accumulates in cancer cells by considerable selectivity, the cancer is destroyed selectively. BNCT was applied to malignant brain tumor (GBM) in USA for 10 years (1951-1961). In Japan the clinical study was done for GBM in 1968, and thereafter, malignant melanoma of the skin was also treated by BNCT using Kyoto University Research Reactor (KUR). In 2001, the first application to the recurrent H&N cancer was performed at KURRI and scored a great sucess. The research team of KURRI have performed a lot of BNCT using KUR neutron beam in collaboration with many co-investrigatiors outside KURRI. The current number of BNCT exceeded 660 (over 50% of total BNCT in the world). It includes several world's first trials represented by case of recurrent head and neck cancers, malignant pleural mesotheliomas, local recurrence of digestive organ cancers and breast cancers. The utility of FBPA PET for sucessful BNCT has been also asscssed. Based on these achievement, we earnestly promoted the project to develop an accelerator BNCT system from 2007. The neutron fluence rate must be high sufficiently and stable at least for 1 hour. An equipment has to casyto operate and small enough in order to install in a hospital. The operation cost of the equipment also have to be inexpensive for the future spread. We chose a cyclotron, 30 MeV proton, over 1 Ma of electric current and a beryllium target. After pre-clinical tests on neutron beam characteristics, phase I clinical test was started in 2012 to examine the safety and acceptability of neutron system, boron compound BPA and their combination. The first target cancer is a recurrent malignat glioma, and the second is an inoperable locally advanced or recurrent head and neck cancer. For malignant glioma, it

  1. Neutron capture therapy. Principles and applications

    International Nuclear Information System (INIS)

    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.

  2. 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)

    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

  3. Basic requirements and parameter optimization for boron neutron capture therapy of extracorporeal irradiated and auto-transplanted organs

    International Nuclear Information System (INIS)

    Background: In 2001 and 2003, at the University of Pavia, Italy, boron neutron capture therapy (BNCT) has been successfully used in the treatment of hepatic colorectal metastases (). The treatment procedure (TAOrMINA protocol) is characterised by the auto-transplantation and extracorporeal irradiation of the liver using a thermal neutron beam. Methods: The clinical use of this approach requires well founded data and an optimized irradiation facility. In order to start with this work and to decide upon its feasibility at the research reactor TRIGA Mainz, basic data and requirements have been considered (). Computer calculations using the ATTILA () and MCNP () codes have been performed, including data from conventional radiation therapy, from the TAOrMINA approach, resulting in reasonable estimations. Results: Basic data and requirements and optimal parameters have been worked out, especially for use at an optimized TRIGA irradiation facility (). Advantages of the extracorporeal irradiation with auto-transplantation and the potential of an optimized irradiation facility could be identified. Within the requirements, turning the explanted organ over by 180° appears preferable to a whole side source, similar to a permanent rotation of the organ. Conclusions: The design study and the parameter optimization confirm the potential of this approach to treat metastases in explanted organs. The results do not represent actual treatment data but a first estimation. Although all specific values refer to the TRIGA Mainz, they may act as a useful guide for other types of neutron sources. The recommended modifications () show the suitability of TRIGA reactors as a radiation source for BNCT of extracorporeal irradiated and auto-transplanted organs. - Highlights: ► The approach to treat metastases in explanted organs allows for more specific optimization. ► A modified TRIGA as a neutron source can achieve promising results in short irradiation times. ► Turning the organ in the

  4. Synovectomy by neutron capture in boron

    International Nuclear Information System (INIS)

    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

  5. 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...

  6. 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)

    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 10B (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).

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

    International Nuclear Information System (INIS)

    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.

  8. 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.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Taewoong; Lee, Hyounggun; Lee, Wonho, E-mail: wonhol@korea.ac.kr

    2015-10-21

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

  11. Current status of neutron capture therapy

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Binello, E.; Yanch, J.C. [Massashucetts Institute of Technology, Cambridge, MA (United States); Shortkroff, S. [Brigham and Women`s Hospital, Boston, MA (United States)

    1997-12-01

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

  13. Radiological protection considerations during the treatment of glioblastoma patients by boron neutron capture therapy at the high flux reactor in Petten, The Netherlands

    International Nuclear Information System (INIS)

    A clinical trial of Boron Neutron Capture Therapy (BNCT) for glioblastoma patients has been in progress at the High Flux Reactor (HFR) at Petten since October 1997. The JRC (as licence holder of the HFR) must ensure that radiological protection measures are provided. The BNCT trial is a truly European trial, whereby the treatment takes place at a facility in the Netherlands under the responsibility of clinicians from Germany and patients are treated from several European countries. Consequently, radiological protection measures satisfy both German and Dutch laws. To respect both laws, a BNCT radioprotection committee was formed under the chairmanship of an independent radioprotection expert, with members representing all disciplines in the trial. A special nuance of BNCT is that the radiation is provided by a mixed neutron/gamma beam. The radiation dose to the patient is thus a complex mix due to neutrons, gammas and neutron capture in boron, nitrogen and hydrogen, which, amongst others, need to be correctly calculated in non-commercial and validated treatment planning codes. Furthermore, due to neutron activation, measurements on the patient are taken regularly after treatment. Further investigations along these lines include dose determination using TLDs and boron distribution measurements using on-line gamma ray spectroscopy. (author)

  14. Development of the epithermal neutron beam and its clinical application for boron neutron capture therapy at the Brookhaven medical research reactor

    International Nuclear Information System (INIS)

    The failures of the Boron Neutron Capture Therapy (BNCT) trials conducted between 1951 and 1961 were attributed to inadequate penetration of the thermal neutron beams and poor localization of boron compound in the tumour. The epithermal neutron beam at the BMRR was designed and installed to improve the penetration of the neutron beam. The use of this epithermal neutron beam for the clinical trial initiated in 1994 at Brookhaven National Laboratory (BNL) was preceded by the neutron beam optimization and characterization, the validation of the treatment planning software and the establishment of a procedure for treatment plan evaluation and dose reporting and recording. To date, a total of 54 patients have been treated. Our experience in the development of the epithermal neutron beam for clinical BNCT at the BMRR may be useful to other investigators desirous of developing similar programs for cancer therapy. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Sakurai, Yoshinori, E-mail: yosakura@rri.kyoto-u.ac.jp; Tanaka, Hiroki; Kondo, Natsuko; Kinashi, Yuko; Suzuki, Minoru; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira [Kyoto University Research Reactor Institute, Asashironishi 2-1010, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan)

    2015-11-15

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

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

    International Nuclear Information System (INIS)

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

  17. 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.

  18. Research needs for neutron capture therapy

    International Nuclear Information System (INIS)

    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

  19. 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.

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

    Science.gov (United States)

    Medina, Daniel C.; Li, Xin; Springer, Charles S., Jr.

    2005-05-01

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

  1. 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)

    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

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

    OpenAIRE

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

    2015-01-01

    Background Neutron capture therapy for glioblastoma has focused mainly on the use of 10B as neutron capture isotope. However, 157Gd 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 f...

  3. Conceptual design project: Accelerator complex for nuclear physics studies and boron neutron capture therapy application at the Yerevan Physics Institute (YerPhI) Yerevan, Armenia

    Energy Technology Data Exchange (ETDEWEB)

    Avagyan, R.H.; Kerobyan, I.A.

    2015-07-15

    The final goal of the proposed project is the creation of a Complex of Accelerator Facilities at the Yerevan Physics Institute (CAF YerPhI) for nuclear physics basic researches, as well as for applied programs including boron neutron capture therapy (BNCT). The CAF will include the following facilities: Cyclotron C70, heavy material (uranium) target/ion source, mass-separator, LINAC1 (0.15–1.5 MeV/u) and LINAC2 (1.5–10 MeV/u). The delivered by C70 proton beams with energy 70 MeV will be used for investigations in the field of basic nuclear physics and with energy 30 MeV for use in applications.

  4. Conceptual design project: Accelerator complex for nuclear physics studies and boron neutron capture therapy application at the Yerevan Physics Institute (YerPhI) Yerevan, Armenia

    Science.gov (United States)

    Avagyan, R. H.; Kerobyan, I. A.

    2015-07-01

    The final goal of the proposed project is the creation of a Complex of Accelerator Facilities at the Yerevan Physics Institute (CAF YerPhI) for nuclear physics basic researches, as well as for applied programs including boron neutron capture therapy (BNCT). The CAF will include the following facilities: Cyclotron C70, heavy material (uranium) target/ion source, mass-separator, LINAC1 (0.15-1.5 MeV/u) and LINAC2 (1.5-10 MeV/u). The delivered by C70 proton beams with energy 70 MeV will be used for investigations in the field of basic nuclear physics and with energy 30 MeV for use in applications.

  5. Conceptual design project: Accelerator complex for nuclear physics studies and boron neutron capture therapy application at the Yerevan Physics Institute (YerPhI) Yerevan, Armenia

    International Nuclear Information System (INIS)

    The final goal of the proposed project is the creation of a Complex of Accelerator Facilities at the Yerevan Physics Institute (CAF YerPhI) for nuclear physics basic researches, as well as for applied programs including boron neutron capture therapy (BNCT). The CAF will include the following facilities: Cyclotron C70, heavy material (uranium) target/ion source, mass-separator, LINAC1 (0.15–1.5 MeV/u) and LINAC2 (1.5–10 MeV/u). The delivered by C70 proton beams with energy 70 MeV will be used for investigations in the field of basic nuclear physics and with energy 30 MeV for use in applications

  6. New carbon-carbon linked amphiphilic carboranyl-porphyrins as boron neutron capture agents

    International Nuclear Information System (INIS)

    Novel amphiphilic carboranyl-porphyrins have been synthesized for Boron Neutron Capture Therapy (BNCT). These compounds have carbon-carbon bonds between the carborane residues and the porphyrin meso-phenyl groups, and contain 28-31% boron by weight . (author)

  7. Boron neutron capture therapy of brain tumors: investigation of urinary metabolites and oxidation products of sodium borocaptate by electrospray ionization mass spectrometry.

    Science.gov (United States)

    Gibson, C R; Staubus, A E; Barth, R F; Yang, W; Kleinholz, N M; Jones, R B; Green-Church, K; Tjarks, W; Soloway, A H

    2001-12-01

    Boron neutron capture therapy (BNCT) is based on a nuclear capture reaction that occurs when boron-10, a stable isotope, is irradiated with low energy neutrons to produce high-energy alpha particles and recoiling lithium-7 nuclei. The purpose of the present study was to determine what urinary metabolites, if any, could be detected in patients with brain tumors who were given sodium borocaptate (BSH), a drug that has been used clinically for BNCT. BSH was infused intravenously over a 1-h time period at doses of 26.5, 44.1, or 88.2 mg/kg of body weight to patients with high-grade brain tumors. Electrospray ionization mass spectrometry has been used to investigate possible urinary metabolites of BSH. Chemical and instrument conditions were established to detect BSH and its possible metabolites in both positive and negative electrospray ionization modes. Using this methodology, boronated ions were found in patients' urine samples that appeared to be consistent with the following chemical structures: BSH sulfenic acid (BSOH), BSH sulfinic acid (BSO(2)H), BSH disulfide (BSSB), BSH thiosulfinate (BSOSB), and a BSH-S-cysteine conjugate (BSH-CYS). Although BSH has been used clinically for BNCT since the late 1960s, this is the first report of specific biotransformation products following administration to patients. Further studies will be required to determine both the biological significance of these metabolites and whether any of these accumulate in significant amounts in brain tumors. PMID:11717178

  8. 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)

    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 10BSH-containing water-in-oil-in-water emulsion (10BSH-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 10BSH-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. • 10B-containing WOW emulsion can be applied as a novel intra-arterial boron carrier for BNCT for HCC

  9. Boron labeled rabbit anti-rat fibrin and goat anti-rabbit gamma globulin antibodies and their potential for slow neutron capture therapy of tumors

    International Nuclear Information System (INIS)

    The therapeutic effectiveness of slow neutron capture therapy is currently dependent upon achieving a high concentration gradient of boron between tumor and normal tissue. Labeling of anti-tumor or anti-tumor site antibodies with boron containing compounds could provide this high therapeutic value. Anti-rat fibrin antibodies, which show considerable localization at the site of several transplantable rat tumors, were labeled with 4-boronophenylalanine (4-BPA) using the N-carboxy anhydride procedure. Activity of these labeled antibodies was studied by modifying the test for fibrinogen concentration of hemophiliac blood. The number of 4-BPAs bound to each active antibody was determined indirectly using the fluorimetric test for phenylalanine concentration in serum. These tests showed that labeled antibodies retained their activity, and it was possible to add up to fifty 4-BPAs per active antibody. The indirect approach to achieving a high therapeutic value of boron was also investigated. This procedure involves labeling anti-immunoglobulin antibodies that bind to anti-tumor antibodies which are already bound to their respective antigens. Indirect labeling has the potential of increasing the therapeutic value by a factor of ten over the direct approach. Activity of labeled goat anti-rabbit gamma globulin (RGG) antibodies was studied by radial immunodiffusion and passive hemagglutination. The number of 4-BPAs bound to each active antibody was determined indirectly by fluorimetry. These labeled antibodies also retained their activity, and it was possible to add upwards of forty 4-BPAs per active antibody

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

    International Nuclear Information System (INIS)

    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 10B content. III. Examination of the distribution of boric substances in living organisms by means of a quantitative analysis of the boron content. (orig./PW)

  11. Gadolinium atom on neutron capture therapy

    International Nuclear Information System (INIS)

    This report describes our measurements of gadolinium concentrations in several brain tumors obtained from fresh surgical specimens, as compared with corresponding concentrations in the blood. Moreover we tried to find out if the gadolinium concentration is high enough to use this compound in the treatment of brain tumors by neutron capture therapy. (J.P.N.)

  12. 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)

    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)

  13. 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 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. PMID:25156017

  14. '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)

    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).

  15. "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).

  16. Early clinical trial concept for boron neutron capture therapy: A critical assessment of the EORTC trial 11001

    International Nuclear Information System (INIS)

    BNCT causes selective damage to tumor cells by neutron capture reactions releasing high LET-particles where 10B-atoms are present. Neither the 10B-compound nor thermal neutrons alone have any therapeutic effect. Therefore, the development of BNCT to a treatment modality needs strategies, which differ from the standard phase I-III clinical trials. An innovative trial design was developed including translational research and a phase I aspect. The trial investigates as surrogate endpoint BSH and BPA uptake in different tumor entities.

  17. Towards gadolinium neutron capture therapy

    International Nuclear Information System (INIS)

    As glioblastoma multiforme has macroscopic areas with poor vascularisation, and thereby poor uptake of an NCT-agent, the long-range γ-rays from GdNCT might enhance dose deposition compared to BNCT and to conformal photon therapy. Multicellular spheroids from a human glioblastoma cell line (Gli-6) were irradiated with conventional X-rays, with neutrons only (from the NRG Argonaut Reactor, LFR), and with neutrons (from the LFR) + 157Gd-DTPA (240 ppm 157Gd). Preliminary results demonstrate that after neutron irradiation in the presence of 157Gd, the spheroids showed growth arrest. By 3D treatment planning calculations on MRI's from patients with brain tumours, dose volume histograms (DVH) for GdNCT were compared to DVH for conventional conformal radiotherapy. The calculations indicate that GdNCT on patients with large, deep-seated tumours yields better tumour/brain dose distribution than conformal radiotherapy. (author)

  18. 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

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

    International Nuclear Information System (INIS)

    Principles, history, clinical trial experiences and future view of the neutron capture therapy are described. The therapy using 10B (boron neutron capture therapy, BNCT) involves the intravenous injection of 10B-containing compound to be accumulated in the tumor and following irradiation of thermal (10B-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.)

  20. Studies on the antitumor activity of boron neutron capture therapy for human p53-mutated oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Mutation of the tumor-suppressing, cell cycle regulating p53 gene in the oral squamous cell carcinoma (OSCC) is seen in more than half of its patient population. The purpose of the present studies is to investigate the in vitro and in vivo effects of boron neutron therapy (BNCT) to OSCC cells with the mutation. OSCC SAS cells used were derived from human lingual tumor and were SAS/mp53 and SAS/neo, which were the recombinants of mutated p53 gene and of neo (neomycin-resistant)/wild type p53 as a control, respectively. For BNCT, borono-phenylalanine (BPA) and thermal neutron flux from Kyoto University Reactor were used. In vitro, cell cultures were irradiated in the presence of BPA (10B, 50 ppm) at a physical dose of 6 Gy/914.5 sec. This dose condition was defined by prior measurement of an actual neutron flux of 1.57 x 109/cm2/sec with Au wire-dosimeter and of concomitant gamma-ray of 9.06 x 10-4 Gy/sec with thermoluminescent dosimeter. In vivo, cells were transplanted subcutaneously in nude mice and at the tumor size of 5 mm, neutron was irradiated for 70 min (8.21 x 1012 n/cm2 in total, measured on site by the Au wire) to the target 2 hr after ip injection of BPA 250 mg/kg (10B, 21.28 mg/kg) with concomitant on site gamma-ray dose of 1.41 Gy in total. Under the condition, total physical dose of neutron to the tumor was found to be around 13 Gy when calculated on the boron tissue levels of about 17 ppm. Results were: p53-mutated cells were resistant to BNCT; BNCT induced G1 and G2/M arrest in SAS/neo and the latter only in SAS/mp53; apoptosis occurred post G1 arrest in the wild type and in the mutant, post G2/M arrest; recurrence was not observable after BNCT in wild type but seen in half of mice with mutated p53 tumor. Treatment to suppress the relapse after BNCT was thus thought necessary in the p53-mutated tumor. (R.T.)

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

    International Nuclear Information System (INIS)

    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

  2. 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

  3. 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.)

  4. 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)

    The cytotoxic effects of locally injected 10B-immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with 10B-immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Histopathologically, hyalinization and necrosis were found in 10B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. We prepared boronated PEG-binding bovine serum albumin (10B-PEG-BSA). 10B concentrations in AsPC-1, human pancreatic cancer cells (2 x 105 /well) obtained 24 hrs after incubation with 10B-PEG-BSA was 13.01 ± 1.74 ppm. The number of 10B atoms delivered to the tumor cells was calculated to be 7.83 x 1011 at 24 hrs after incubation with 10B-PEG-BSA. These data indicated that the 10B-PEG-BSA could deliver a sufficient amount of 10B atoms (more than 109 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 10B-PEG BSA or 10B-cationic liposome. We had demonstrated the 10B-PEG BSA or 10B-cationic liposome is taken up by AsPC-1 tumor tissue to a much greater extent than by normal tissues. (J.P.N.)

  5. “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.

  6. Design calculations of an epithermal neutron beam and development of a treatment planning system for the renovation of thor for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Tsing Hua University was recently granted by National Science Council a five-year project to renovate its Open-Pool reactor (THOR) for boron neutron capture therapy. With this support, the whole graphite blocks in the original thermal column region can be removed for redesigning and constructing a better epithermal neutron beam. THOR is a 1 MW research reactor. The cross section area of the core facing the thermal column is 60 cm x 50 cm. By using 60 cm FLUENTAL plus 10 cm Pb, with cross section area of 70 cm x 60 cm and surrounded by 6 cm thick PbF2 reflector, the epithermal neutron flux at the filter/moderator exit can reach ∼8.5 x 109 n/cm2/s. When the collimator is added, the epithermal neutron beam intensity at the beam exit is reduced to 3 x 109 n/cm2/sec, but is still six times higher than the previous beam. Facing the clinical trials scheduled 3 and half years from now, a preliminary version of treatment planning system is developed. It includes a pre-processor to read CT scan and post-processors to display dose distributions. (author)

  7. Development and characteristics of the HANARO ex-core neutron irradiation facility for applications in the boron neutron capture therapy field

    CERN Document Server

    Kim, M S; Jun, B J; Kim, H; Lee, B C; Hwang, Sung-Yul; Jun, Byung-Jin; Kim, Heonil; Kim, Myong-Seop; Lee, Byung-Chul

    2006-01-01

    The HANARO ex-core neutron irradiation facility was developed for various applications in the boron neutron capture therapy (BNCT) field, and its characteristics have been investigated. In order to obtain a sufficient thermal neutron flux with a low level contamination of fast neutrons and gamma-rays, a radiation filtering method is adopted. The radiation filter has been designed by using a silicon single crystal cooled by liquid nitrogen and a bismuth crystal. The installation of the main components of the irradiation facility and the irradiation room are finished. Experimental measurements of the neutron beam characteristics have been performed by using bare and cadmium covered gold foils and wires. The in-phantom neutron flux distribution was measured for a flux mapping inside the phantom. The gamma-ray dose was determined by using TLD-700 thermoluminescence dosimeters. The thermal and fast neutron fluxes and the gamma-ray dose were calculated by using the MCNP code, and they were compared with experimenta...

  8. Effect of the p53 gene status on the sensitivity of oral squamous cell carcinoma cells to boron neutron capture therapy

    International Nuclear Information System (INIS)

    The role of the p53 gene in the sensitivity of oral squamous cell carcinoma (SCC) to boron neutron capture therapy (BNCT) had not been studied. We examined the effect of boronophenylalanine (BPA)-mediated BNCT on oral SCC cells showing either wild-type p53 (SAS/neo) or mutated-type p53 (SAS/mp53). Survival ratio of cells was determined by colony formation. Cell viability was measured by MTT assay. Apoptotic cells were evaluated by flow cytometric analysis and nuclear DNA staining. When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo cells as compared with SAS/mp53. The proportion of apoptotic cells with DNA fragmentation was also increased in the cells with functional p53. These results suggest that oral SCC cells with mutated p53 cells are more resistant to BNCT than those with wild-type p53. BNCT must inhibit oral SCC cells in p53-dependent and p53-independent mechanisms. (author)

  9. Comparison of intracerebral delivery of carboplatin and photon irradiation with an optimized regimen for boron neutron capture therapy of the F98 rat glioma

    Energy Technology Data Exchange (ETDEWEB)

    Barth, Rolf F., E-mail: rolf.barth@osumc.edu [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Yang Weilian; Huo Tianyao [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Riley, Kent J.; Binns, Peter J. [Nuclear Reactor Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Grecula, John C., E-mail: john.grecula@osumc.edu [James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Ohio State University, Columbus, OH, 43210 (United States); Gupta, Nilendu, E-mail: nilendu.gupta@osumc.edu [James Cancer Hospital and Solove Research Institute, Department of Radiation Oncology, Ohio State University, Columbus, OH, 43210 (United States); Rousseau, Julia, E-mail: julia.rousseau@yahoo.fr [INSERM, U836, Institute of Neurosciences, Grenoble (France); Elleaume, Helene, E-mail: h.elleaume@esrf.fr [INSERM, U836, Institute of Neurosciences, Grenoble (France)

    2011-12-15

    In this report we have summarized our studies to optimize the delivery of boronophenylalanine (BPA) and sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) of F98 glioma bearing rats. These results have been compared to a chemoradiotherapeutic approach using the same tumor model. The best survival data from our BNCT studies were obtained using a combination of BPA and sodium borocaptate BSH administered via the internal carotid artery, in combination with blood-brain barrier disruption (BBB-D). This treatment resulted in a mean survival time (MST) of 140 d with a 25% cure rate. The other approach combined intracerebral administration of carboplatin by either convection enhanced delivery (CED) or Alzet pump infusion, followed by external beam photon irradiation. This resulted in MSTs of 83 d and 112 d, respectively, with a cure rate of 40% for the latter. However, a significant problem that must be solved for both BNCT and this new chemoradiotherapeutic approach is how to improve drug uptake and microdistribution within the tumor.

  10. Comparison of intracerebral delivery of carboplatin and photon irradiation with an optimized regimen for boron neutron capture therapy of the F98 rat glioma

    International Nuclear Information System (INIS)

    In this report we have summarized our studies to optimize the delivery of boronophenylalanine (BPA) and sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) of F98 glioma bearing rats. These results have been compared to a chemoradiotherapeutic approach using the same tumor model. The best survival data from our BNCT studies were obtained using a combination of BPA and sodium borocaptate BSH administered via the internal carotid artery, in combination with blood–brain barrier disruption (BBB-D). This treatment resulted in a mean survival time (MST) of 140 d with a 25% cure rate. The other approach combined intracerebral administration of carboplatin by either convection enhanced delivery (CED) or Alzet pump infusion, followed by external beam photon irradiation. This resulted in MSTs of 83 d and 112 d, respectively, with a cure rate of 40% for the latter. However, a significant problem that must be solved for both BNCT and this new chemoradiotherapeutic approach is how to improve drug uptake and microdistribution within the tumor.

  11. 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.

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

    International Nuclear Information System (INIS)

    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 (10BPA) 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 4 106 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 10B 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 (R2 = 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 (R2 = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual

  13. 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

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

    International Nuclear Information System (INIS)

    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-CO2H 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 10B concentration of 22 ppm in tumor tissues was achieved by the injection of Tf-PEG-CL liposome at 7.2 mg/kg body weight 10B 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)

  15. Identification of early and distinct glioblastoma response patterns treated by boron neutron capture therapy not predicted by standard radiographic assessment using functional diffusion map

    International Nuclear Information System (INIS)

    Radiologic response of brain tumors is traditionally assessed according to the Macdonald criteria 10 weeks from the start of therapy. Because glioblastoma (GB) responds in days rather than weeks after boron neutron capture therapy (BNCT) that is a form of tumor-selective particle radiation, it is inconvenient to use the Macdonald criteria to assess the therapeutic efficacy of BNCT by gadolinium-magnetic resonance imaging (Gd-MRI). Our study assessed the utility of functional diffusion map (fDM) for evaluating response patterns in GB treated by BNCT. The fDM is an image assessment using time-dependent changes of apparent diffusion coefficient (ADC) in tumors on a voxel-by-voxel approach. Other than time-dependent changes of ADC, fDM can automatically assess minimum/maximum ADC, Response Evaluation Criteria In Solid Tumors (RECIST), and the volume of enhanced lesions on Gd-MRI over time. We assessed 17 GB patients treated by BNCT using fDM. Additionally, in order to verify our results, we performed a histopathological examination using F98 rat glioma models. Only the volume of tumor with decreased ADC by fDM at 2 days after BNCT was a good predictor for GB patients treated by BNCT (P value = 0.022 by log-rank test and 0.033 by wilcoxon test). In a histopathological examination, brain sections of F98 rat glioma models treated by BNCT showed cell swelling of both the nuclei and the cytoplasm compared with untreated rat glioma models. The fDM could identify response patterns in BNCT-treated GB earlier than a standard radiographic assessment. Early detection of treatment failure can allow a change or supplementation before tumor progression and might lead to an improvement of GB patients’ prognosis

  16. 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.

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

    International Nuclear Information System (INIS)

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, D; Jung, J; Suh, T [The Catholic University of Korea, College of medicine, Department of biomedical engineering (Korea, Republic of)

    2014-06-01

    Purpose: Purpose of paper is to confirm the feasibility of acquisition of three dimensional single photon emission computed tomography (SPECT) image from boron neutron capture therapy (BNCT) using Monte Carlo simulation. Methods: In case of simulation, the pixelated SPECT detector, collimator and phantom were simulated using Monte Carlo n particle extended (MCNPX) simulation tool. A thermal neutron source (<1 eV) was used to react with the boron uptake region (BUR) in the phantom. Each geometry had a spherical pattern, and three different BURs (A, B and C region, density: 2.08 g/cm3) were located in the middle of the brain phantom. The data from 128 projections for each sorting process were used to achieve image reconstruction. The ordered subset expectation maximization (OSEM) reconstruction algorithm was used to obtain a tomographic image with eight subsets and five iterations. The receiver operating characteristic (ROC) curve analysis was used to evaluate the geometric accuracy of reconstructed image. Results: The OSEM image was compared with the original phantom pattern image. The area under the curve (AUC) was calculated as the gross area under each ROC curve. The three calculated AUC values were 0.738 (A region), 0.623 (B region), and 0.817 (C region). The differences between length of centers of two boron regions and distance of maximum count points were 0.3 cm, 1.6 cm and 1.4 cm. Conclusion: The possibility of extracting a 3D BNCT SPECT image was confirmed using the Monte Carlo simulation and OSEM algorithm. The prospects for obtaining an actual BNCT SPECT image were estimated from the quality of the simulated image and the simulation conditions. When multiple tumor region should be treated using the BNCT, a reasonable model to determine how many useful images can be obtained from the SPECT could be provided to the BNCT facilities. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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 10B dynamics in ocular melanoma and the surrounding normal tissues, to evaluate the possibility of applying BNCT to ocular melanoma. In three ocular melanoma patients, 10B concentration in melanoma after administration of 10B-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 10B1-BPA. (author)

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

    Science.gov (United States)

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

    2009-07-01

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

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

    International Nuclear Information System (INIS)

    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 7.1x109 n cm-2 s-1 and the fast neutron flux was 2.5x106 n cm-2 s-1, indicating a very well-thermalized neutron field with negligible fast neutron dose. For radiobiological studies it was necessary to shield the body of the hamster from the neutron flux while exposing the everted cheek pouch bearing the tumors. To that end we developed a lithium (enriched to 95% in 6Li) 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.

  3. 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.

  4. Boron Neutron Capture Therapy (BNCT) in an Oral Precancer Model: Therapeutic Benefits and Potential Toxicity of a Double Application of BNCT with a Six-Week Interval

    International Nuclear Information System (INIS)

    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.

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

    International Nuclear Information System (INIS)

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

  6. 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

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

    International Nuclear Information System (INIS)

    Objective: BNCT is a binary treatment modality based on the nuclear reactions that occur when boron (10B) 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 10B 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 10B 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 10B concentration was observed at the end of the infusion and scaled as a linear function of the administered dose. The 10B concentration in the scalp and in the GBM tissue was higher than in blood by 1.5 x and at least 3.5 x

  8. Progress in neutron capture therapy for cancer

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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

  10. 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)

    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(Na210B10H10) 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- 10+BPA

  11. Biodistribution of the boron carriers boronophenylalanine (BPA) and/or decahydrodecaborate (GB-10) for Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases

    International Nuclear Information System (INIS)

    BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25–76 ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung. - Highlights: • We performed experimental boron biodistribution studies for lung metastases. • 3 protocols employing BPA and GB-10 would be therapeutically useful. • BNCT at RA-3 would be potentially therapeutic for experimental lung metastases

  12. Capillary electrophoresis-electrospray mass spectrometry and HR-ICP-MS for the detection and quantification of 10B-boronophenylalanine (10B-BPA) used in boron neutron capture therapy.

    Science.gov (United States)

    Pitois, Aurélien; de las Heras, Laura Aldave; Zampolli, Antonella; Menichetti, Luca; Carlos, Ramon; Lazzerini, Guido; Cionini, Luca; Salvatori, Pietro Alberto; Betti, Maria

    2006-02-01

    Boron neutron capture therapy (BNCT) is a bimodal radiotherapeutic treatment based on the irradiation of neoplastic tissues with neutrons after the tissues have selectively accumulated molecules loaded with nuclides with large neutron capture cross-sections (such boron-10). Boron-10 carriers have been tested to a limited extent, and clinical trials have been conducted on sulfhydryl borane (10B-BSH) and boronophenylalanine (10B-BPA). However, precise and accurate measurements of boron-10 concentrations (0.1-100 microg/g) in specimens and samples of limited size (microg scale) are needed in order to be able to biologically characterise new compounds in predictive tissue dosimetry, toxicology and pharmacology studies as well as in clinical investigations. A new approach based on fast separation and detection of 10B-BPA performed by coupling capillary electrophoresis to electrospray mass spectrometry is reported. This method allows the quantitative analysis and characterisation of 10B-BPA in a short time with a high separation efficiency. Detection limits of 3 microM for 10B-BPA and 30 ng/mL for 10B were obtained with CE-ESI-MS. A quantification limit of 10 microM for 10B-BPA (100 ng/mL for 10B) was attained. The total boron-10 concentration was determined by high-resolution inductively coupled mass spectrometry in order to validate the method. Boron-10 isotope measurements were carried out by HR-ICP-MS at medium resolution (R=4000) due to the presence of an isobaric interference at mass 10. Good agreement was obtained between the values from CE-ESI-MS and those from HR-ICP-MS. The method has been successfully used to determine the 10B-BPA in two lines of cultured cells. PMID:16372182

  13. Research on neutron capture therapy in the USSR

    International Nuclear Information System (INIS)

    Research on neutron capture therapy in the USSR began in 1964. Towards 1975 prime knowledge in physics, pharmacology and radiobiology had been accumulated. It was realized that inherent to NCT is a variety of modalities as to the type and location of the tumor, the energy and source of neutrons, the nature and transportation of the nuclide-carrying agent (NCA), etc. Thus, it became likely that some modalities would turn out to be clinically feasible. At the end of the 70s, studies of boron derivatives began at the All-Union Oncological Research Center, Moscow. These studies were stimulated by the clinical trials in Japan. Still, neutron capturing nuclides (NCN) other than 10b are regarded as promising. Research was aimed at clinical trials that could ensure sufficient safety, convenience and conclusiveness. Hence, new requirements emerged, such as the pre-clinical modeling of NCT in big animals and the monitoring of tumor response to each fraction of NCT. Usual requirements are also to be met, that is: tailoring neutron beams with an adequate intensity and energy, choosing NCNs and finding suitable NCAs, physical and radiobiological planning including adoption of tentative RBEs and time-fractionation regimen, selecting tumors as candidates for NCT, and developing techniques for monitoring NCNs in vivo

  14. Carborane compounds for neutron capture therapy of malignant melanoma

    International Nuclear Information System (INIS)

    The possibility of using thiouracil as a vehicle for stable nuclei such as 10B for neutron capture therapy (NCT) of melanoma was first discussed by Fairchild and co-workers in 1982. The author's research has been directed towards the design and synthesis of a number of o-carboranyl-thiouracils, the ten boron atoms of the carborane cage having a clear advantage for NCT. The first step was the preparation, previously reported, of thiouracils bearing an alkyl group continuing a triple bond for later elaboration to a carborane. The present paper describes the continuation of this work with the preparation of the carboranes of this series and its extension to the synthesis of a thiouracil in which a carboranylalkyl group is attached to the nitrogen in the 3-position

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

    International Nuclear Information System (INIS)

    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.)

  16. 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

    Science.gov (United States)

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

    2013-01-01

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

  17. 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.

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

    International Nuclear Information System (INIS)

    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[ae-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.

  19. Boron neutron capture therapy of EGFR or EGFRvIII positive gliomas using either boronated monoclonal antibodies or epidermal growth factor as molecular targeting agents

    Energy Technology Data Exchange (ETDEWEB)

    Yang, W. [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Barth, R.F. [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States)], E-mail: rolf.barth@osumc.edu; Wu, G. [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Tjarks, W. [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Binns, P.; Riley, K. [Nuclear Reactor Laboratory and Department of Nuclear Engineering, Massachusetts Institute of Technology, Cambridge, MA 02215 (United States)

    2009-07-15

    In the present report we have summarized studies carried out over the past five years on molecular targeting of the epidermal growth factor receptor (EGFR) and its mutant isoform, EFGRvIII, for BNCT of genetically engineered F98 rat gliomas, expressing either wildtype (F98{sub EGFR}) or mutant receptors (F98{sub npEGFRvIII}). EGF or the monoclonal antibodies (mAbs), cetuximab (IMC-C225) and L8A4, which recognize wildtype EGFR and EGFRvIII, respectively, were heavily boronated using polyamidoamine (PAMAM) dendrimers (BD) linked to the targeting vehicles by means of heterobifunctional reagents. Boronated EGF or mAbs, alone or in combination with i.v. boronophenylalanine (BPA), were administered intracerebrally (i.c.) by either intratumoral (i.t.) injection or convection enhanced delivery (CED) to rats bearing F98 gliomas following which BNCT was initiated. The best survival data were obtained in rats bearing F98{sub npEGFRvIII} gliomas that had received CED of BD-L8A4 either alone or in combination with i.v. boronophenylalanine (BPA). Studies carried out in rats bearing composite tumors (F98{sub EGFR}/F98{sub npEGFRvIII}) demonstrated that it was essential to target both tumor cell populations in order to obtain an optimal therapeutic effect. Based on these observations, we have concluded that EGFR targeting vehicles are useful, but not stand-alone boron delivery agents due to the heterogeneity of receptor expression in brain tumors. They could, however, be quite useful in combination with the two drugs that currently are being used clinically, BPA and sodium borocaptate (BSH) for BNCT of either brain tumors or head and neck cancers.

  20. 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.

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

    International Nuclear Information System (INIS)

    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)

  2. A computational study into the use of polyacrylamide gel and A-150 plastic as brain tissue substitutes for boron neutron capture therapy

    International Nuclear Information System (INIS)

    A precise evaluation of the dosimetric performance of epithermal neutron beams designed for boron neutron capture theory of brain tumours requires the use of a phantom material that closely matches brain tissue. The aim of this study was to investigate how well polyacrylamide gel (or PAG) and A-150 plastic performed as substitutes for brain tissue compared with standard phantom materials such as water and polymethyl-methacrylate (or PMMA). Thermal neutron fluence, photon dose and epithermal neutron dose distributions were calculated for the epithermal neutron beam available at the University of Birmingham. The results presented in this paper show that the PAG provides a good simulation of radiation transport in the brain with differences from the real brain of + 9.4%, -10.8% and + 5.1% at a depth of 50 mm for thermal neutron fluence, gamma dose and epithermal neutron dose distributions respectively. The polyacrylamide gel presented is therefore a promising substitute for brain tissue that can, as a dosimeter, provide a three-dimensional map of the absorbed dose delivered by the epithermal neutron beam. However, this study does not investigate the agreement between doses derived from magnetic resonance and physical doses for such gels. A-150 plastic was shown to be a better substitute for brain tissue than PMMA, with differences from brain of -1.9%, -12.4% and -13.2% at a depth of 50 mm for thermal neutron fluence, gamma dose and epithermal neutron dose distributions respectively, against + 21.1%, -16.2% and + 19.2% for PMMA. A-150 plastic should therefore be the material of choice for solid phantoms. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Schinazi, Raymond F.

    2004-12-01

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

  4. Carboranyl Oligonucleotides for Neutron Capture Therapy Final Report

    International Nuclear Information System (INIS)

    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

  5. Boron neutron capture synovectomy at SINQ in Switzerland

    International Nuclear Information System (INIS)

    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 β-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 β-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 permanent

  6. General considerations for neutron capture therapy at a reactor facility

    International Nuclear Information System (INIS)

    In addition to neutron beam intensity and quality, there are also a number of other significant criteria related to a nuclear reactor that contribute to a successful neutron capture therapy (NCT) facility. These criteria are classified into four main categories: Nuclear design factors, facility management and operations factors, facility resources, and non-technical factors. Important factors to consider are given for each of these categories. In addition to an adequate neutron beam intensity and quality, key requirements for a successful neutron capture therapy facility include necessary finances to construct or convert a facility for NCT, a capable medical staff to perform the NCT, and the administrative support for the facility. The absence of any one of these four factors seriously jeopardizes the overall probability of success of the facility. Thus nuclear reactor facility management considering becoming involved in neutron capture therapy, should it be proven clinically successful, should take all these factors into consideration. (author)

  7. Online detection of radiation produced in Boron-10 neutron capture reaction: preliminary studies

    International Nuclear Information System (INIS)

    Boron microdistribution in both tumor and normal tissue sections can be studied by the autoradiography technique in solid state nuclear track detectors (SSNTD). A measurement of boron concentration in tissue is obtained through the evaluation of the density of tracks produced by alpha and lithium ions generated in the neutron capture reaction 10B(n,α) 7Li. This knowledge is pivotal when a BNCT (Boron Neutron Capture Therapy) protocol is considered. A new methodology is proposed in order to record alpha and lithium events in real time, as light spots superimposed to the tissue section image. CCD (Charge-Coupled Device) and CMOS (Complementary Metal Oxide Semiconductor) are used as detectors, with the advantage of avoiding the superposition of events. Commercial web cams were employed for the preliminary experiments. They were partially disassembled in order to get the sensor chip uncovered. These devices were exposed to different radiation sources: 6.118 MeV alpha particles (252Cf), 0.662 MeV gamma rays (137Cs) and thermal neutrons (moderated 241Am-Be source, 103n.cm2.seg-1), to analyze the characteristics of the respective images. Pictures from tissue sections put in contact with the sensor surface were also acquired. A software was developed in Matlab to perform the image capture and processing. Early results show the feasibility of using these devices to study the distribution 10B in tissue samples. (author)

  8. 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

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

    International Nuclear Information System (INIS)

    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 7LiF thermoluminescence detector is evaluated. This method was suggested by the group headed by Dr. Grazia Gambarini. The dosemeters used were TLD-600 (6LiF:Mg,Ti with 95.6% 6Li) and TLD-700 (7LiF:Mg,Ti with 99.9% 7LiF) 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, with representative

  10. 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)

    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 10B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of 10B 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 10BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), 10BSH 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 10B 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 10B entrapped WOW emulsion could be

  11. 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

  12. Damage-repair processes in thermal neutron capture therapy

    International Nuclear Information System (INIS)

    Radiobiological specificity of thermal neutron capture therapy was examined using cultured cell lines of B16 mouse melanoma cells and of V79 Chinese hamster cells, with particular reference to the recovery from sublethal radiation damage (SLD) and potentially lethal radiation damage (PLD). A boron compound used was 10B1-para-boronophenylalanine (10B1-BPA). Cell survival curves of B16 melanoma cells irradiated with thermal neutrons alone had no shoulders. Cells treated with 10B1-BPA followed by thermal neutron irradiation showed remarkably enhanced killing in proportion to the concentration of 10B1-BPA. Neither B16 cells nor V79 cells possessed the ability to repair SLD. The B16 cells possessed little ability to repair 10B1-BPA plus thermal neutrons-induced PLD. Some cells possessed the ability to sequentially repair PLD when caffeine was added to the cell medium during irradiation. B16 cells efficiently repaired x ray-induced slow type PLD, but could not repair thermal neutron-induced PLD or 10B1-BPA plus thermal neutron-induced PLD. V79 cells possessed a greater ability to repair both x ray-induced PLD and thermal neutron-induced PLD than B16 melanoma cells. (Namekawa, K.)

  13. Mutagenic effect of boronophenylalanine and borocaptate in neutron capture therapy

    International Nuclear Information System (INIS)

    To investigate the mutagenic effect in BNCT, CHO cells were incubated for 2 hours or 20 hours in culture medium with borocaptate sodium (BSH: Na2B12H11SH), or boronophenylalanine (BPA) prior exposure to neutrons from the heavy water facility of the Kyoto University Research Reactor (KUR) and the occurrence of mutations at the HPRT locus was measured. The mutagenicity of BSH and BPA was almost similar to the mutagenicity of 10B-boric acid at the same 10B concentration when cells were irradiated by iso-survival neutron dose. Pre-incubation to BSH for 20 hours caused an increase both in the cell killing effect and mutagenic effect in boron neutron capture therapy (BNCT) compared with pre-incubation to BSH for 2 hours. However, pre-incubation to BPA for 20 hours caused an increase in the cell killing effect but induced a decrease in mutagenic effect in BNCT compared with pre-incubation to BPA for 2 hours. (author)

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

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

  16. 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)

    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)

  17. Accelerator based neutron source for neutron capture therapy

    International Nuclear Information System (INIS)

    Full text: The Budker Institute of Nuclear Physics (Novosibirsk) and the Institute of Physics and Power Engineering (Obninsk) have proposed an accelerator based neutron source for neutron capture and fast neutron therapy for hospital. Innovative approach is based upon vacuum insulation tandem accelerator (VITA) and near threshold 7Li(p,n)7Be neutron generation. Pilot accelerator based neutron source for neutron capture therapy is under construction now at the Budker Institute of Nuclear Physics, Novosibirsk, Russia. In the present report, the pilot facility design is presented and discussed. Design features of facility components are discussed. Results of experiments and simulations are presented. Complete experimental tests are planned by the end of the year 2005

  18. Evaluation of absorbed dose in Gadolinium neutron capture therapy

    OpenAIRE

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

    2015-01-01

    Gadolinium neutron capture therapy (GdNCT) is used for treatment of radioresistant malignant tumors. The absorbed dose in GdNCT can be divided into four primary dose components: thermal neutron, fast neutron, photon and natural gadolinium doses. The most significant is the dose created by natural gadolinium. The amount of gadolinium at the irradiated region is changeable and depends on the gadolinium delivery agent and on the structure of the location where the agent i...

  19. Determination of liposomal boron biodistribution in tumor bearing mice by using neutron capture autoradiography

    International Nuclear Information System (INIS)

    It is necessary to accumulate the 10B atoms selectively to the tumor cells for effective boron neutron capture therapy (BNCT). In order to achieve accurate measurements of 10B concentrations in biological samples, we employ a technique of neutron capture autoradiography (NCAR) of the sliced whole body samples of tumor bearing mice using CR- 39 plastic track detectors. The CR-39 detectors attached with samples were exposed to thermal neutrons in the thermal column of the TRIGA II reactor at the Institute for Atomic Energy, Rikkyo University. We obtained NCAR images for mice injected intraveneously by 10B-polyethylene-glycol (PEG) binding liposome or 10B-bare liposome. The 10B concentrations in the tumor tissue of mice were estimated by means of alpha and lithium track density measurements. In this study, we increased the accumulation of 10B atoms in the tumor tissues by binding PEG chains to the surface of liposome, which increase the retension in the blood flow and escape the phagocytosis by reticulo-endotherial systems. Therefore, 10B-PEG liposome is a candidate for an effective 10B carrier in BNCT.(author)

  20. 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)

    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)

  1. 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.

  2. Maleimide-functionalized closo-dodecaborate albumin conjugates (MID-AC): Unique ligation at cysteine and lysine residues enables efficient boron delivery to tumor for neutron capture therapy.

    Science.gov (United States)

    Kikuchi, Shunsuke; Kanoh, Daisuke; Sato, Shinichi; Sakurai, Yoshinori; Suzuki, Minoru; Nakamura, Hiroyuki

    2016-09-10

    Maleimide-conjugating closo-dodecaborate sodium form 5c (MID) synthesized by the nucleophilic ring-opening reaction of closo-dodecaborate-1,4-dioxane complex 2 with tetrabutylammonium (TBA) azide was found to conjugate to free SH of cysteine and lysine residues in BSA under physiological conditions, forming highly boronated BSA that showed high and selective accumulation in tumor and significant tumor growth inhibition in colon 26 tumor-bearing mice subjected to thermal neutron irradiation. PMID:27422608

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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, F98npEGFRvIII. A heavily boronated polyamidoamine (PAMAM) dendrimer (BD) was linked to L8A4 by means of heterobifunctional reagents. Wild type (F98WT) receptor(-) or EGFRvIII human gene transfected receptor(+) F98npEGFRvIII glioma cells were implanted into the brains of Fischer rats. Biodistribution studies were initiated 14 d later. Animals received 125I-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 10B/∼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)

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

    International Nuclear Information System (INIS)

    Neutron capture therapy for glioblastoma has focused mainly on the use of 10B as neutron capture isotope. However, 157Gd 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 157Gd 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 the

  6. 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. PMID:24387907

  7. Synthesis of triazolyl methyl-substituted amino- and oxy-undeca-hydro-dodeca-borates for potential application in boron neutron capture therapy

    International Nuclear Information System (INIS)

    A general approach to the synthesis of triazole conjugates containing undeca-hydro-closo-dodeca-borate anions based on Huisgen 1, 3-dipolar cycloaddition is presented. Un-decahydro-closo-dodeca-borate anions bearing terminal alkyne groups were synthesized by the reaction of H3N-B12H11- or HO-B12H112- with alkyne halides in N, N-dimethylformamide using KOH as a base. Variation of reaction time, alkyne halide concentration and steric demands of the alkyne halide resulted in the stepwise introduction of one to three alkyne groups into H3N-B12H11-. Two compounds {(CHCCH2)-N-B12H11- and (CHCCH2)O-B12H112-} were crystallized for single-crystal X-ray diffraction studies. N- and O-alkyne un-decahydro-closo-dodeca-borate anions reacted with various functionalized azides including lipid, carborane, aryl and hydroxyalkyl groups. The current study provides various synthetic applications not only for BNCT but also for boron cluster materials. (authors)

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

    Energy Technology Data Exchange (ETDEWEB)

    Jung, J; Yoon, D; Suh, T [The catholic University of Korea, College of Medicine/Graduate School of Medicine, Seoul (Korea, Republic of); Hong, K [Molecular Imaging Program at Stanford (MIPS), Palo Alto, CA (United States)

    2014-06-01

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

  9. 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)

    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

  10. Intercomparison of inductively coupled plasma mass spectrometry, quantitative neutron capture radiography, and prompt gamma activation analysis for the determination of boron in biological samples.

    Science.gov (United States)

    Schütz, C L; Brochhausen, C; Hampel, G; Iffland, D; Kuczewski, B; Otto, G; Schmitz, T; Stieghorst, C; Kratz, J V

    2012-10-01

    Boron determination in blood and tissue samples is a crucial task especially for treatment planning, preclinical research, and clinical application of boron neutron capture therapy (BNCT). Comparison of clinical findings remains difficult due to a variety of analytical methods, protocols, and standard reference materials in use. This paper addresses the comparability of inductively coupled plasma mass spectrometry, quantitative neutron capture radiography, and prompt gamma activation analysis for the determination of boron in biological samples. It was possible to demonstrate that three different methods relying on three different principles of sample preparation and boron detection can be validated against each other and yield consistent results for both blood and tissue samples. The samples were obtained during a clinical study for the application of BNCT for liver malignancies and therefore represent a realistic situation for boron analysis. PMID:22918535

  11. Intercomparison of inductively coupled plasma mass spectrometry, quantitative neutron capture radiography, and prompt gamma activation analysis for the determination of boron in biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Schuetz, C.L. [University of Mainz, Institute for Nuclear Chemistry, Mainz (Germany); Johannes Gutenberg-University of Mainz, Institute for Nuclear Chemistry, Mainz (Germany); Brochhausen, C. [University of Mainz, Institute of Pathology, Mainz (Germany); Hampel, G.; Iffland, D.; Schmitz, T.; Stieghorst, C.; Kratz, J.V. [University of Mainz, Institute for Nuclear Chemistry, Mainz (Germany); Kuczewski, B. [Regional Council Darmstadt, Darmstadt (Germany); Otto, G. [University of Mainz, Department of Hepatobiliary, Pancreatic and Transplantation Surgery, Mainz (Germany)

    2012-10-15

    Boron determination in blood and tissue samples is a crucial task especially for treatment planning, preclinical research, and clinical application of boron neutron capture therapy (BNCT). Comparison of clinical findings remains difficult due to a variety of analytical methods, protocols, and standard reference materials in use. This paper addresses the comparability of inductively coupled plasma mass spectrometry, quantitative neutron capture radiography, and prompt gamma activation analysis for the determination of boron in biological samples. It was possible to demonstrate that three different methods relying on three different principles of sample preparation and boron detection can be validated against each other and yield consistent results for both blood and tissue samples. The samples were obtained during a clinical study for the application of BNCT for liver malignancies and therefore represent a realistic situation for boron analysis. (orig.)

  12. Intercomparison of inductively coupled plasma mass spectrometry, quantitative neutron capture radiography, and prompt gamma activation analysis for the determination of boron in biological samples

    International Nuclear Information System (INIS)

    Boron determination in blood and tissue samples is a crucial task especially for treatment planning, preclinical research, and clinical application of boron neutron capture therapy (BNCT). Comparison of clinical findings remains difficult due to a variety of analytical methods, protocols, and standard reference materials in use. This paper addresses the comparability of inductively coupled plasma mass spectrometry, quantitative neutron capture radiography, and prompt gamma activation analysis for the determination of boron in biological samples. It was possible to demonstrate that three different methods relying on three different principles of sample preparation and boron detection can be validated against each other and yield consistent results for both blood and tissue samples. The samples were obtained during a clinical study for the application of BNCT for liver malignancies and therefore represent a realistic situation for boron analysis. (orig.)

  13. 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

  14. Selective thermal neutron capture therapy of cancer cells using their specific functional differentiation

    International Nuclear Information System (INIS)

    The theory and the history of selective thermal neutron capture therapy for malignant melanoma, thermal neutron capture therapy which has been developed by authors, synthesis and effects of 10B-compounds accumulating in melanoma cells and absorbing thermal neutron easily, and many experiments concerning this therapy were reviewed and discussed. (Tsunoda, M.)

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

    International Nuclear Information System (INIS)

    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)

  16. 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)

  17. Dosimetry methods in boron neutron capture therapy

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    This paper describes mainly development studies on the determination method of in vivo 10B 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 10B concentration in the diseased part. This study aimed at in vivo 10B 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 10B (n, αγ)7Li 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 10B concentration and error analysis derived by the authors. As for the effect of prompt γ-rays of 23Na(n, γ)24Na and 6Li(n, γ)7Li 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 10B 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.)

  19. The production of nitrogen-13 by neutron capture in boron compounds

    International Nuclear Information System (INIS)

    The 10B(α,n)13N reaction is studied as an activation process in a variety of solid boron-containing neutron shielding materials. The source of α-particles is the neutron capture reaction 10B(n,α)7Li. Samples of boron carbide, boron oxide, and boron nitride are irradiated with thermal neutrons and the rate of 13N production is determined. 13N promptly decays, emitting a positron. This positron efficiently annihilates with electrons in the material and the resultant 511 keV gamma ray is detected. For each of the above-mentioned materials, the rate of 13N production is (1-2) x 10-10 per captured neutron

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

    International Nuclear Information System (INIS)

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10B carriers in tumors followed by irradiation with thermal or epithermal neutrons. The high linear energy transfer alpha particles and recoiling 7Li nuclei emitted during the capture of a thermal neutron by a 10B 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 (Na210B1-0H10), 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 10B/kg iv + GB-10 50 mg 10B/kg iv; BPA 46.5 mg 10B/kg ip; BPA 46.5 mg 10B/kg ip + iv; BPA 46

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  3. Characteristics of neutron irradiation facility and dose estimation method for neutron capture therapy at Kyoto University research reactor institute

    International Nuclear Information System (INIS)

    The neutron irradiation characteristics of the Heavy Water Neutron Irradiation Facility (HWNIF) at the Kyoto University Research Reactor Institute (KIJRRI) for boron neutron capture therapy (BNCT), is described. The present method of dose measurement and its evaluation at the KURRI, is explained. Especially, the special feature and noticeable matters were expounded for the BNCT with craniotomy, which has been applied at present only in Japan. (author)

  4. Simultaneous Observation of Cells and Nuclear Tracks from the Boron Neutron Capture Reaction by UV-C Sensitization of Polycarbonate.

    Science.gov (United States)

    Portu, Agustina; Rossini, Andrés Eugenio; Thorp, Silvia Inés; Curotto, Paula; Pozzi, Emiliano César Cayetano; Granell, Pablo; Golmar, Federico; Cabrini, Rómulo Luis; Martin, Gisela Saint

    2015-08-01

    The distribution of boron in tissue samples coming from boron neutron capture therapy protocols can be determined through the analysis of its autoradiography image on a nuclear track detector. A more precise knowledge of boron atom location on the microscopic scale can be attained by the observation of nuclear tracks superimposed on the sample image on the detector. A method to produce an "imprint" of cells cultivated on a polycarbonate detector was developed, based on the photodegradation properties of UV-C radiation on this material. Optimal conditions to generate an appropriate monolayer of Mel-J cells incubated with boronophenylalanine were found. The best images of both cells and nuclear tracks were obtained for a neutron fluence of 1013 cm-2, 6 h UV-C (254 nm) exposure, and 4 min etching time with a KOH solution. The imprint morphology was analyzed by both light and scanning electron microscopy. Similar samples, exposed to UV-A (360 nm) revealed no cellular imprinting. Etch pits were present only inside the cell imprints, indicating a preferential boron uptake (about threefold the incubation concentration). Comparative studies of boron absorption in different cell lines and in vitro evaluation of the effect of diverse boron compounds are feasible with this methodology. PMID:26155721

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

    International Nuclear Information System (INIS)

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

  6. Dose calculation from a D-D-reaction-based BSA for boron neutron capture synovectomy

    International Nuclear Information System (INIS)

    Monte Carlo simulations were carried out to calculate dose in a knee phantom from a D-D-reaction-based Beam Shaping Assembly (BSA) for Boron Neutron Capture Synovectomy (BNCS). The BSA consists of a D(d,n)-reaction-based neutron source enclosed inside a polyethylene moderator and graphite reflector. The polyethylene moderator and graphite reflector sizes were optimized to deliver the highest ratio of thermal to fast neutron yield at the knee phantom. Then neutron dose was calculated at various depths in a knee phantom loaded with boron and therapeutic ratios of synovium dose/skin dose and synovium dose/bone dose were determined. Normalized to same boron loading in synovium, the values of the therapeutic ratios obtained in the present study are 12-30 times higher than the published values.

  7. Dose calculation from a D-D-reaction-based BSA for boron neutron capture synovectomy

    Energy Technology Data Exchange (ETDEWEB)

    Abdalla, Khalid [Department of Physics, Hail University, Hail (Saudi Arabia)], E-mail: khalidafnan@uoh.edu.sa; Naqvi, A.A. [Department of Physics, King Fahd University of Petroleum and Minerals and Center for Applied Physical Sciences, Box No. 1815, Dhahran 31261 (Saudi Arabia)], E-mail: aanaqvi@kfupm.edu.sa; Maalej, N.; Elshahat, B. [Department of Physics, King Fahd University of Petroleum and Minerals and Center for Applied Physical Sciences, Box No. 1815, Dhahran 31261 (Saudi Arabia)

    2010-04-15

    Monte Carlo simulations were carried out to calculate dose in a knee phantom from a D-D-reaction-based Beam Shaping Assembly (BSA) for Boron Neutron Capture Synovectomy (BNCS). The BSA consists of a D(d,n)-reaction-based neutron source enclosed inside a polyethylene moderator and graphite reflector. The polyethylene moderator and graphite reflector sizes were optimized to deliver the highest ratio of thermal to fast neutron yield at the knee phantom. Then neutron dose was calculated at various depths in a knee phantom loaded with boron and therapeutic ratios of synovium dose/skin dose and synovium dose/bone dose were determined. Normalized to same boron loading in synovium, the values of the therapeutic ratios obtained in the present study are 12-30 times higher than the published values.

  8. Malignant melanoma cure by selective thermal neutron capture therapy

    International Nuclear Information System (INIS)

    Thermal neutrons are easily absorbed by the nonradioactive isotope 10B, resulting in the emission of alpha particles and lithium atoms, which release an energy of 2.33 MeV for up to a 14-μm-diam melanoma cell. Thus, if 10B can be selectively accumulated in melanoma, it can be destroyed without injury to the surrounding normal tissues by concentrating high linear energy transfer particles. The authors have synthesized seven melanoma-seeking 10B compounds, two of which, 10B12-chlorpromazine(10B12-CPZ) and 10B1-p-boronophenylalanine(10B1-BPA), are found to be highly effective. The enhanced melanoma-killing effect of the 10B compounds is found by in vitro radiobiological analysis. A chemical assay and alpha-track analysis 28 h after systemic administration to melanoma-bearing hamsters reveals a 10B melanoma/blood ratio of 11.5 and a melanoma/liver ratio of 15. Establishment of a clinical therapeutic method for curing human melanoma without failure is underway by correlating biophysical, biochemical, biological, and therapeutic data analysis. Recently, the authors have also been working to develop neutron capture therapy using 10B-monoclonal antibodies for melanoma and were able to make some 10B conjugates with the specific m259-0 antibody

  9. 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)

  10. Neutron capture therapy for cancer: development at the National Atomic Energy Commission

    International Nuclear Information System (INIS)

    Boron neutron capture therapy (BNCT) involves the concurrent presence of a flux of neutrons of adequate energy and Boron 10 as a capture agent. They interact to damage tumor cells but fail to produce significant damage to healthy tissue because the destructive effect occurs mainly in the tumor cells that have selectively accumulated boron. This technique is applied for the treatment of brain tumors of the glioblastoma multiform type and melanoma in different locations. The aim of this project at CNEA is to develop the technological, scientific, clinical know-how and facilities to undertake clinical trials in Argentina. The development of the irradiation facility, the clinical beam and dosimetry was developed at the RA-6 reactor, Bariloche Atomic Center. Treatment planning, instrumentation for the neutron beam, boron measurements, neutron beam for small animal irradiation at the RA-1 reactor and basic research in radiobiology, microdosimetry and autoradiography were developed at Constituyentes Atomic Center. It is also conducted an intense activity in accelerator based BNCT. The infusions to be injected to the patients are prepared at Ezeiza Atomic Center. The clinics of BNCT radiotherapy is developed at the Roffo Institute of Oncology and the neurosurgery at the Argerich Hospital. At present, the project is close to start in the following months to treat melanoma in the limbs, when the authorization procedure is completed. (author)

  11. Evaluation of the dose enhancement of combined 10B + 157Gd Neutron Capture Therapy (NCT)

    International Nuclear Information System (INIS)

    An innovative molecule, GdBLDL, for boron neutron capture therapy (BNCT) has been developed and its effectiveness as a BNCT carrier is currently under evaluation using in vivo experiments on small animal tumour models. The molecule contains both 10B (the most commonly used NCT agent) and 157Gd nuclei. 157Gd is the second most studied element to perform NCT, mainly thanks to its high cross section for the capture of low-energy neutrons. The main drawback of 157Gd neutron capture reaction is the very short range and low-energy secondary charged particles (Auger electrons), which requires 157Gd to be very close to the cellular DNA to have an appreciable biological effect. Treatment doses were calculated by Monte Carlo simulations to ensure the optimised tumour irradiation and the sparing of the healthy organs of the irradiated animals. The enhancement of the absorbed dose due to the simultaneous presence of 10B and 157Gd in the experimental set-up was calculated and the advantage introduced by the presence of 157Gd was discussed. (authors)

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

    International Nuclear Information System (INIS)

    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 D2O 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.)

  13. Neutron capture therapy signal-to-noise ratio distribution for deep seated brain tumors

    International Nuclear Information System (INIS)

    Boron and Gadolinium Neutron Capture Therapy effects are modelled using COG, a Monte Carlo radiation transport code developed and tested at Lawrence Livermore National Laboratory (LLNL) and MCNP. Calculations were performed to analyze the effect of various gadolinium concentrations on dose distribution and cell-kill effect of the GdNCT modality and to determine the optimum therapeutic conditions for treating the brain cancers. Results showed that a concentration of 100 ppm gadolinium, resulting in a signal-to-noise ratio of 1.53, was most beneficial for a deep seated tumor irradiated with an epithermal beam. A concentration of 1000 ppm, producing a ratio of 1.41, may still be advantageous, as the dose is increased without compromising the tumor to normal tissue dose ratio. The ratio decreases substantially to 1.15 for a concentration of 5000 ppm, suggesting such a high concentration may be deleterious. Calculations were also done for alternate tumor locations. (author)

  14. Accelerator based neutron source for the neutron capture therapy at hospital

    International Nuclear Information System (INIS)

    Accelerator source of epithermal neutrons for the hospital-based boron neutron capture therapy is proposed and discussed. Kinematically collimated neutrons are produced via near-threshold 7Li(p, n)7Be reaction at proton energies of 1.883 - 1.9 MeV. Steady-state accelerator current of 40 mA allows to provide therapeutically useful beams with treatment times of tens of minutes. The basic components of the facility are a hydrogen negative ion source, an electrostatic tandem accelerator with vacuum insulation, a sectioned rectifier, and a thin lithium neutron generating target on the surface of tungsten disk cooled by liquid metal heat carrier. Design features of facility components are discussed. The possibility of stabilization of proton energy is considered. At proton energy of 2.5 MeV the neutron beam production for NCT usage after moderation is also considered. (author)

  15. A standardized method for beam design in neutron capture therapy

    International Nuclear Information System (INIS)

    A desirable end point for a given beam design for Neutron Capture Therapy (NCT) should be quantitative description of tumour control probability and normal tissue damage. Achieving this goal will ultimately rely on data from NCT human clinical trials. Traditional descriptions of beam designs have used a variety of assessment methods to quantify proposed or installed beam designs. These methods include measurement and calculation of open-quotes free fieldclose quotes parameters, such as neutron and gamma flux intensities and energy spectra, and figures-of-merit in tissue equivalent phantoms. The authors propose here a standardized method for beam design in NCT. This method would allow all proposed and existing NCT beam facilities to be compared equally. The traditional approach to determining a quantitative description of tumour control probability and normal tissue damage in NCT research may be described by the following path: Beam design → dosimetry → macroscopic effects → microscopic effects. Methods exist that allow neutron and gamma fluxes and energy dependence to be calculated and measured to good accuracy. By using this information and intermediate dosimetric quantities such as kerma factors for neutrons and gammas, macroscopic effect (absorbed dose) in geometries of tissue or tissue-equivalent materials can be calculated. After this stage, for NCT the data begins to become more sparse and in some areas ambiguous. Uncertainties in the Relative Biological Effectiveness (RBE) of some NCT dose components means that beam designs based on assumptions considered valid a few years ago may have to be reassessed. A standard method is therefore useful for comparing different NCT facilities

  16. In vitro determination of toxicity, binding, retention, subcellular distribution and biological efficacy of the boron neutron capture agent DAC-1

    International Nuclear Information System (INIS)

    In boron neutron capture therapy (BNCT), 10B is delivered selectively to the tumour cells and the nuclide then forms high-LET radiation (4He2+ and 7Li3+) upon neutron capture. Today much research is focused on development of a variety of boron compounds aimed for BNCT. The compounds must be thoroughly analysed in preclinical tests regarding basic characteristics such as binding and subcellular distribution to enable accurate estimations of dose-modifying factors. DAC-1, 2-[2-(3-amino-propyl)-1,2-dicarba-closo-dodecaboran(12)-1-yl-methoxyl]-1,3 -propanediol was synthesized at our laboratories and the human colon carcinoma cells LS-174T were used as an in vitro model. The boron compound showed a remarkable intracellular accumulation, 20-100 times higher than the boron content in the culture medium, in cultured cells and was not removed by extensive washes. Approximately half of the boron taken up also remained within the cells for at least 4 days. The DAC-1 compound alone was not toxic at boron concentrations below 2.5 μg B/g. The intracellular distribution of the boron compound was investigated by subcellular fractionation experiments and low pH treatments. It is possible that DAC-1 binds to some intracellular molecules or to membranes connected with organelles in the cytoplasm or even to the inside of the outer cell membrane. Another possibility is that the compound, due to the somewhat lipophilic properties, is embedded in the membranes. Thermal neutron irradiations were carried out at the Brookhaven Medical Research Reactor (BMRR). At a survival level of 0.1, DAC-1 + thermal neutrons were about 10.5 times more effective in cell inactivation than the thermal neutrons alone. Monte Carlo calculations gave a mean value of the 10B-dependent specific energy, the dose, of 0.22 Gy. The total physical dose during irradiation of DAC-1-containing cells with a neutron fluence of 0.18 x 1012 n/cm2 was 0.39 Gy. The dose-modifying factor, at survival level 0.1, when comparing

  17. In vitro determination of toxicity, binding, retention, subcellular distribution and biological efficacy of the boron neutron capture agent DAC-1.

    Science.gov (United States)

    Tilly, N; Olsson, P; Hartman, T; Coderre, J; Makar, M; Malmquist, J; Sjöberg, S; Pettersson, J; Carlsson, J; Glimelius, B

    1996-01-01

    In boron neutron capture therapy (BNCT), 10B is delivered selectively to the tumour cells and the nuclide then forms high-LET radiation (4He2+ and 7Li3+) upon neutron capture. Today much research is focused on development of a variety of boron compounds aimed for BNCT. The compounds must be thoroughly analysed in preclinical tests regarding basic characteristics such as binding and subcellular distribution to enable accurate estimations of dose-modifying factors. DAC-1,2-[2-(3-amino-propyl)-1,2-dicarba-closo-dodecaboran (12)-1-yl-methoxy]- 1,3-propanediol was synthesized at our laboratories and the human colon carcinoma cells LS-174T were used as an in vitro model. The boron compound showed a remarkable intracellular accumulation, 20-100 times higher than the boron content in the culture medium, in cultured cells and was not removed by extensive washes. Approximately half of the boron taken up also remained within the cells for at least 4 days. The DAC-1 compound alone was not toxic at boron concentrations below 2.5 micrograms B/g. The intracellular distribution of the boron compound was investigated by subcellular fractionation experiments and low pH treatments. It is possible that DAC-1 binds to some intracellular molecules or to membranes connected with organelles in the cytoplasm or even to the inside of the outer cell membrane. Another possibility is that the compound, due to the somewhat lipophilic properties, is embedded in the membranes. Thermal neutron irradiations were carried out at the Brookhaven Medical Research Reactor (BMRR). At a survival level of 0.1, DAC-1 + thermal neutrons were about 10.5 times more effective in cell inactivation than the thermal neutrons alone. Monte Carlo calculations gave a mean value of the 10B-dependent specific energy, the dose, of 0.22 Gy. The total physical dose during irradiation of DAC-1-containing cells with a neutron fluence of 0.18 x 10(12) n/cm2 was 0.39 Gy. The dose-modifying factor, at survival level 0.1, when

  18. A PC-based computer program for the estimation of the radiation dose in vitro and in vivo boron neutron capture irradiation experiments

    International Nuclear Information System (INIS)

    In Boron Neutron Capture Therapy (BNCT) microdosimetry of charged particle radiation depends on total boron concentration and intracellular boron distribution. Due to the inhomogeneity of boron distribution in cells, radiation doses to both tumor and normal tissue are influenced by boron and nitrogen concentrations and intracellular distributions, cell volume and shape, nuclear size and geometrical structure of the tissue. For correct calculation of the radiation dose in BNCT, these factors should be taken into account. Several computer models have been developed previously in order to estimate the absorbed dose from charged particles in BNCT (Gabel et al.; Kobayashi and Kanda). In these models, however, single values for mean Relative Biological Effectiveness (RBE) are used to convert high LET radiation doses to isoeffective photon equivalent doses. The RBE depends on both LET and endpoint, such as surviving fraction of tumor cells or normal tissue tolerance (Barendsen et al.). Since LET is not constant along the track of a charged particle, the RBE cannot be considered constant for particles generated by boron and nitrogen neutron capture. Experimental RBE data to be used in BNCT have been gathered, but without consensus (Gabel et al.; Fukuda et al.). A computer program designed to run on a microcomputer has been written in Turbo Pascal to determine energy deposition in cell nuclei resulting from charged particle emission after boron or nitrogen neutron capture in nuclear, cytoplasmic and extracellular compartments. This computer model goes beyond former models in estimating a microscopic RBE for each individual charged particle track segment that traverses a cell nucleus. Another refinement is the implementation of dynamic modelling, which offers a more realistic simulation of cell and tissue geometry. This was approached by varying cell geometry and arrangement parameters within a simulation

  19. 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

  20. Role of the TAPIRO fast research reactor in neutron capture therapy in Italy. Calculations and measurements

    International Nuclear Information System (INIS)

    For Neutron Capture Therapy (NCT) applications, many research reactors are presently utilized. Clinical trials are performed in thermal reactors that have been appropriately modified, in order to obtain convenient beams for Becton (Boron Neutron Capture Therapy), by means of proper filtering or spectrum shifting. However, the beam quality obtainable by fast reactors is expected to be better than that of thermal reactor facilities. Tapiro is a low power, high flux, highly enriched (93.5%) 235Uranium fast reactor. The power is 5 kw and the maximum neutron flux in the core is 3.2'1012 cm-2 s-1. A thermal column and an epithermal one have been designed and constructed, aimed at dosimetry and animal experiments. The configurations of the columns have been designed by means of calculations based on Monte Carlo with the codes MCNP4B and MCNPX2.1.5 together with the DSA (Direct Statistical Approach) variance reduction optimisation patch. The columns have been characterized by means of measurements performed with activation techniques and thermoluminescence and gel dosimeters. Experimental results have shown good consistency with calculations. Moreover, they have confirmed the good quality of the beams obtainable with such a reactor. The TAPIRO reactor (a) and the scheme of the epithermal column (b) are shown. To have further confirmation of the quality of the radiation field in the constructed epithermal column, in-phantom absorbed doses have been measured and profiled by means of gel dosimeters, separating the various dose contributions having different biological effects. An epithermal column for human clinical trials has been designed by means of Monte Carlo calculations and the construction is now in progress. A section of this column is shown and beam parameters are reported. It is evident that the beam quality of this column is satisfactory in comparison with the IAEA recommendations. Moreover, such parameters are good if compared with those available at the

  1. Electroporation increases the effect of borocaptate (10B-BSH) in neutron capture therapy

    International Nuclear Information System (INIS)

    Purpose: The cell membrane permeability of borocaptate (10B-BSH) and its extent of accumulation in cells are controversial. This study was performed to elucidate these points. Methods and Materials: Two different treatments were applied to SCCVII tumor cells. The first group of tumor cells was incubated in culture medium with 10B-BSH or 10B-enriched boric acid, and was exposed to neutrons from the heavy water facility of the Kyoto University Reactor (KUR). More than 99% of neutrons were thermal neutrons at flux base. The second group was pretreated by electroporation in combination with 10B-BSH, and thereafter the cells were irradiated with neutrons. The cell killing effects of boron neutron capture therapy (BNCT) using BSH were investigated by colony formation assay. Results: Surviving cell fraction decreased exponentially with neutron fluence, and addition of BSH significantly enhanced the cell killing effect of neutron capture therapy (NCT) depending on 10B concentration. The effect of BSH-BNCT also increased with preincubation time of cells in the medium containing BSH. The electroporation of cells with BSH at 10 ppm 10B markedly enhanced BSH-BNCT effects in comparison with that of preincubation alone. The effect of BSH-BNCT with electroporation was equal to that of BNCT using 10B-boric acid at a same 10B concentration (10 ppm). Conclusions: BSH is suggested to penetrate the cells slowly and remained after washing. Electroporation can introduce BSH into the cells very efficiently, and BSH stays in the cells and is not lost by washing. Therefore, if electroporation is applied to tumors after BSH injection, 10B remains in tumors but is cleared from normal tissues, and selective accumulation of 10B in tumors will be achieved after an adequate waiting time

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  5. Noble gas excimer scintillation following neutron capture in boron thin films

    CERN Document Server

    McComb, Jacob C; al-Sheikhly, Mohamed; Thompson, Alan K; Vest, Robert E; Clark, Charles W

    2014-01-01

    Far-ultraviolet (FUV) scintillation signals have been measured in heavy noble gases (argon, krypton, xenon) following boron-neutron capture ($^{10}$B($n,\\alpha$)$^7$Li) in $^{10}$B thin films. The observed scintillation yields are comparable to the yields from some liquid and solid neutron scintillators. At noble gas pressures of 10$^7$ kPa, the number of photons produced per neutron absorbed following irradiation of a 1200 nm thick $^{10}$B film was 14,000 for xenon, 11,000 for krypton, and 6000 for argon. The absolute scintillation yields from the experimental configuration were calculated using data from (1) experimental irradiations, (2) thin-film characterizations, (3) photomultiplier tube calibrations, and (4) photon collection modeling. Both the boron films and the photomultiplier tube were characterized at the National Institute of Standards and Technology. Monte Carlo modeling of the reaction cell provided estimates of the photon collection efficiency and the transport behavior of $^{10}$B($n,\\alpha$...

  6. Design of an accelerator-based neutron source for neutron capture therapy

    International Nuclear Information System (INIS)

    The boron neutron capture therapy is mainly suited in the treatment of some tumor kinds which revealed ineffective to the traditional radiotherapy. In order to take advantage of such a therapeutic modality in hospital environments, neutron beams of suitable energy and flux levels provided by compact size facilities are needed. The advantages and drawbacks of several neutron beams are here analysed in terms of therapeutic gains. In detail the GEANT-3/MICAP simulations show that high tumor control probability, with sub-lethal dose at healthy tissues, can be achieved by using neutron beams of few keV energy having a flux of about 109 neutrons/(cm2 s). To produce such a neutron beam, the feasibility of a proton accelerator is investigated. In particular an appropriate choice of the radiofrequency parameters (modulation, efficiency of acceleration, phase shift, etc.) allows the development of relatively compact accelerators, having a proton beam current of 30 mA and an energy of 2 MeV, which could eventually lead to setting up of hospital-based neutron facilities.

  7. Basic study for development of new tumor specific agents for neutron capture therapy

    International Nuclear Information System (INIS)

    New tissue specific agents for neutron capture therapy was studied. Monoclonal labeled gadolinium-DTPA (Gd-MoAb) and porphyrin (ATN-10)-Gd-DTPA (Gd-ATN10) were studied as possible agents by using 9-L experimental brain tumor model. The tissue concentration were analyzed with magnetic resonance imaging (MRI) and inductively coupled plasma (ICP) analyzer. Gd-MoAb showed persistent retention in the tumor on MRI, but tissue gadolinium concentration was not detectable in the tumor by ICP analyzer, while there was high accumulation of Gd-MoAb in the liver. Gd-ATN10 showed prolonged and high accumulation in the tumor up to 48 hours on MRI. Gadolinium concentration reached up to 9 ppm in the tumor by 0.02 mmol/kg administration, but it disappeared within 6 hours after administration. This dissociation between MRI and ICP analysis was due to separation of ATN-10 and Gd-DTPA. As conclusions, the porphyrin compounds are potential agents for delivering gadolinium or boron specific to the tumor tissue, thus further improvement such as more stable conjugation between porphyrinfic to the tumor tissue, thus further improvement such as more stable conjugation between porphyrin and Gd-DTPA is needed. (author)

  8. Gadolinium as an element for neutron capture therapy

    International Nuclear Information System (INIS)

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

  9. Further development of thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma

    International Nuclear Information System (INIS)

    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.)

  10. To gadolinium using for neutron capture therapy researches at WWR-SM reactor

    International Nuclear Information System (INIS)

    The analysis of using gadolinium (isotope and natural) for the medical purposes in neutron-capture therapy of cancer diseases is carried out. Results of definition of the epithermal neutron beam irradiation dose for biological objects with gadolinium-containing preparations are presented by using the WWR-SM reactor. (authors)

  11. Pre-clinical neutron capture therapy trials at M.I.T. using Na2B12H11SH

    International Nuclear Information System (INIS)

    Pre-clinical neutron capture therapy (NCT) trials with neonate beagles bearing transplanted cerebral tumors were carried out at the MITR-II research reactor medical therapy facility and are presented with a preliminary discussion of earlier studies conducted to determine the NCT dose tolerance to the normal canine brain. The boron compound administered, Na2B12H11SH (92% 10B enriched), was incorporated in the tumor as a result of the breakdown of the physiological blood-brain barrier. Pre- and post-irradiation tumor growth was monitored by computerized axial tomography scanning aided with contrast enhancement. Clinical, radiological, and pathological assessments were performed, revealing positive, though episodic, results of therapy, and are described

  12. Treatment planning and dosimetry for the Harvard-MIT Phase I clinical trial of cranial neutron capture therapy

    International Nuclear Information System (INIS)

    Purpose: A Phase I trial of cranial neutron capture therapy (NCT) was conducted at Harvard-MIT. The trial was designed to determine maximum tolerated NCT radiation dose to normal brain. Methods and Materials: Twenty-two patients with brain tumors were treated by infusion of boronophenylalanine-fructose (BPA-f) followed by exposure to epithermal neutrons. The study began with a prescribed biologically weighted dose of 8.8 RBE (relative biologic effectiveness) Gy, escalated in compounding 10% increments, and ended at 14.2 RBE Gy. BPA-f was infused at a dose 250-350 mg/kg body weight. Treatments were planned using MacNCTPlan and MCNP 4B. Irradiations were delivered as one, two, or three fields in one or two fractions. Results: Peak biologically weighted normal tissue dose ranged from 8.7 to 16.4 RBE Gy. The average dose to brain ranged from 2.7 to 7.4 RBE Gy. Average tumor dose was estimated to range from 14.5 to 43.9 RBE Gy, with a mean of 25.7 RBE Gy. Conclusions: We have demonstrated that BPA-f-mediated NCT can be precisely planned and delivered in a carefully controlled manner. Subsequent clinical trials of boron neutron capture therapy at Harvard and MIT will be initiated with a new high-intensity, high-quality epithermal neutron beam

  13. 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.

  14. 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)

    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 7Li(p,n)7Be. 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.

  15. 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.

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

    International Nuclear Information System (INIS)

    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

  17. Boron determination in liver tissue by combining quantitative neutron capture radiography (QNCR) and histological analysis for BNCT treatment planning at the TRIGA Mainz.

    Science.gov (United States)

    Schütz, C; Brochhausen, C; Altieri, S; Bartholomew, K; Bortolussi, S; Enzmann, F; Gabel, D; Hampel, G; Kirkpatrick, C J; Kratz, J V; Minouchehr, S; Schmidberger, H; Otto, G

    2011-09-01

    The typical primary malignancies of the liver are hepatocellular carcinoma and cholangiocarcinoma, whereas colorectal liver metastases are the most frequently occurring secondary tumors. In many cases, only palliative treatment is possible. Boron neutron capture therapy (BNCT) represents a technique that potentially destroys tumor tissue selectively by use of externally induced, locally confined secondary particle irradiation. In 2001 and 2003, BNCT was applied to two patients with colorectal liver metastases in Pavia, Italy. To scrutinize the rationale of BNCT, a clinical pilot study on patients with colorectal liver metastases was carried out at the University of Mainz. The distribution of the (10)B carrier (p-borono-phenylalanine) in the liver and its uptake in cancerous and tumor-free tissue were determined, focusing on a potential correlation between the uptake of p-borono-phenylalanine and the biological characteristics of cancerous tissue. Samples were analyzed using quantitative neutron capture radiography of cryosections combined with histological analysis. Methodological aspects of the combination of these techniques and results from four patients enrolled in the study are presented that indicate that the uptake of p-borono-phenylalanine strongly depends on the metabolic activity of cells. PMID:21692653

  18. 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)

    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).

  19. Investigation of magnevist pharmacokinetics for calculation of absorbed dose at neutron-capture therapy

    International Nuclear Information System (INIS)

    Full text: The neutron-capture therapy with use of gadolinium-containing pharmacological preparations is one of perspective and not enough investigated directions of application of neutron irradiation in medicine. At definition of the absorbed dose of neutron-capture therapy one of important questions is definition of concentration gadolinium and pharmacokinetics in irradiated tumour. In the given study has been investigated pharmacokinetics of gadolinium-containing preparation 'Magnevist' at intratumoral injection in inoculated tumours of sarcoma C180 at mice. For 'Magnevist' detection its property of radioopacity has been used. In experiments to mice with inoculated tumours C180 the various doses of 'Magnevist' (0.1, 0.2, 0.3 and 0.4 ml) were injected into tumour centre. X-ray images were made before 'Magnevist' injection (control) and after preparation injection every 5 minutes within one hour. It has been shown that at dose 0.1 ml 'Magnevist' eliminated from tumour within 10 minutes. At higher doses of preparation more slow elimination of 'Magnevist' from injection site was observed. Obtained results allow with sufficient accuracy to calculate the time of presence of optimum concentration of 'Magnevist' in tumour at intratumoral injection. It in turn gives the chance to calculate precisely the absorbed dose at irradiation by beam of epi-thermal neutrons. (author)

  20. Assessment of Proton Microbeam Analysis of 11B for Quantitative Microdistribution Analysis of Boronated Neutron Capture Agent Analogs in Biological Tissues

    International Nuclear Information System (INIS)

    The purpose is to assess the 11B(p, α) 8Be* nuclear reaction for quantitatively mapping the in-vivo sub-cellular distribution of boron within gliosarcoma tumors treated with boronated neutron capture therapy agent (NCTA) analogs. Intracranial tumors were produced in Fisher 344 rats using a 9L gliosarcoma model. Fourteen days later, the majority of rats were treated with f-boronophenylalanine and sacrificed 30 or 180 minutes after intravenous injection. Freeze dried tumor cryosections were imaged using the 11B(p, α) 8Be* nuclear reaction and proton microbeams obtained from the nuclear microprobe at Lawrence Livermore National Laboratory. With 11B(p, α) 8Be* analysis, 11B distributions within cells can be quantitatively imaged with spatial resolutions down to 1.5 μm, minimum detection limits of 0.8 mg/kg and acquisition times of several hours. These capabilities offer advantages over alpha track autoradiography, electron energy loss spectroscopy and secondary ion mass spectrometry (SIMS) for 11B quantitation in tissues. However, the spatial resolution, multi-isotope capability and analysis times achieved with SIMS are superior to those achieved with 11B(p, α) 8Be* analysis. When accuracy in quantitation is crucial, the 11B(p, α) 8Be* reaction is well suited for assessing the microdistribution of 11B. Otherwise, SIMS may well be better suited to image the microdistribution of boron associated with NCTAs in biological tissues.

  1. Novel dodecaborate cluster lipids for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Lipids containing the closo-dodecaborate cluster have been developed. Two examples, S-(N,N-(2-dimyristoyloxyethyl) -acetamido)-thioundecahydro-closo-dodecaborate (2-) (B-6-14) and S-(N,N-(2-dipalmitoyloxyethyl) -acetamido)-thioundecahydro-closo-dodecaborate (2-) (B-6-16) have been prepared. With helper lipids, stable liposomes were obtained. (author)

  2. Boron neutron capture therapy: An interdisciplinary co-operation

    International Nuclear Information System (INIS)

    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)

  3. Final Report: 8th International Symposium on Neutron Capture Therapy (NCT) for Cancer, May 15, 1998 - May 15, 1999

    International Nuclear Information System (INIS)

    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

  4. Phantom experiment of depth-dose distributions for gadolinium neutron capture therapy

    International Nuclear Information System (INIS)

    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)

  5. BINP pilot accelerator-based neutron source for neutron capture therapy

    International Nuclear Information System (INIS)

    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 7Li(p,n)7Be 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)

  6. Dosimetric characteristics of the thermal neutron beam facility for neutron capture therapy at Hanaro reactor

    International Nuclear Information System (INIS)

    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/cm2·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)

  7. A microdosimetric study of {sup 10}B(n,{alpha}){sup 7}Li and {sup 157}Gd(n,{gamma}) reactions for neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, C.K.C.; Sutton, M.; Evans, T.M. [Georgia Inst. of Tech., Atlanta, GA (United States); Laster, B.H. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.

    1999-01-01

    This paper presents the microdosimetric analysis for the most interesting cell survival experiment recently performed at the Brookhaven National Laboratory (BNL). In this experiment, the cells were first treated with a gadolinium (Gd) labeled tumor-seeking boronated porphyrin (Gd-BOPP) or with BOPP alone, and then irradiated with thermal neutrons. The resulting cell-survival curves indicate that the {sup 157}Gd(n,{gamma}) reactions are very effective in cell killing. The death of a cell treated with Gd-BOPP was attributed to either the {sup 10}B(n,{alpha}){sup 7}Li reactions or the {sup 157}Gd(n,{gamma}) reactions (or both). However, the quantitative relationship between the two types of reaction and the cell-survival fraction was not clear. This paper presents the microdosimetric analysis for the BNL experiment based on the measured experimental parameters, and the results clearly suggest a quantitative relationship between the two types of reaction and the cell survival fraction. The results also suggest new research in gadolinium neutron capture therapy (GdNCT) which may lead to a more practical modality than the boron neutron capture therapy (BNCT) for treating cancers.

  8. Analysis of boron, samarium and gadolinium in rock samples by neutron capture gamma-ray spectrometry

    International Nuclear Information System (INIS)

    Prompt gamma neutron activation analysis (PGNAA) is useful for determining many of the elements found in sedimentary rocks. It is particularly suitable for the trace elements boron, samarium and gadolinium. The sensitivity of detection can be of the order of 0.1 ppm with an adequate neutron source. Twenty-five sedimentary rock samples were analyzed in the PGNAA facility at the University of Missouri Research Reactor. The materials included Ottawa sand, Berea sandstone, Royer dolomite and several other formations of interest in the petroleum industry. Results of the analyses are presented. Correlations of gadolinium and samarium and of boron with the sum of samarium and gadolinium are given. (author)

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

    International Nuclear Information System (INIS)

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

  10. Analysis of boron, samarium and gadolinium in rock samples by neutron capture gamma ray spectrometry

    International Nuclear Information System (INIS)

    Prompt gamma neutron activation analysis (PGNAA) is useful for determining many of the elements found in sedimentary rocks. It is particularly suitable for the trace elements boron, samarium and gadolinium. The sensitivity of detection can be of the order of 0.1 part per million with an adequate neutron source. Twenty-five sedimentary rock samples were analyzed in the PGNAA facility at the University of Missouri Research Reactor. The materials included Ottawa sand, Berea sandstone, Royer dolomite and several other formations of interest in the petroleum industry. Results of the analyses are presented. Correlations of gadolinium and samarium and of boron with the sum of samarium and gadolinium are given. (author). 8 refs, 2 figs, 4 tabs

  11. Assessment of Proton Microbeam Analysis of 11B for Quantitative Microdistribution Analysis of Boronated Neutron Capture Agent Analogs in Biological Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Bench, G; Grant, P G; Ueda, D L; Autry-Conwell, S A; Hou, Y; Boggan, J E

    2002-12-04

    Purpose: To assess the {sup 11}B(p, {alpha}){sup 8}Be* nuclear reaction for quantitatively mapping the in-vivo sub-cellular distribution of boron within gliosarcoma tumors treated with boronated neutron capture therapy agent (NCTA) analogs. Materials and Methods: Intracranial tumors were produced in Fisher 344 rats using a 9L gliosarcoma model. Fourteen days later, the majority of rats were treated with f-boronophenylalanine and sacrificed 30 or 180 minutes after intravenous injection. Freeze dried tumor cryosections were imaged using the {sup 11}B(p, {alpha}){sup 8}Be* nuclear reaction and proton microbeams obtained from the nuclear microprobe at Lawrence Livermore National Laboratory. Results/Discussion: With{sup 11}B(p, {alpha}){sup 8}Be* analysis, {sup 11}B distributions within cells can be quantitatively imaged with spatial resolutions down to 1.5 {micro}m, minimum detection limits of 0.8 mg/kg and acquisition times of several hours. These capabilities offer advantages over alpha track autoradiography, electron energy loss spectroscopy and secondary ion mass spectrometry (SIMS) for 'B quantitation in tissues. However, the spatial resolution, multi-isotope capability and analysis times achieved with SIMS are superior to those achieved with {sup 11}B(p, {alpha}){sup 8}Be* analysis. Conclusions: When accuracy in quantitation is crucial, the assessing the microdistribution of {sup 11}B. {sup 11}B(p, {alpha}){sup 8}Be* reaction is well suited for Otherwise, SIMS may well be better suited to image the microdistribution of boron associated with NCTAs in biological tissues.

  12. Accelerator-based neutron source for the neutron-capture and fast neutron therapy at hospital

    Science.gov (United States)

    Bayanov, B. F.; Belov, V. P.; Bender, E. D.; Bokhovko, M. V.; Dimov, G. I.; Kononov, V. N.; Kononov, O. E.; Kuksanov, N. K.; Palchikov, V. E.; Pivovarov, V. A.; Salimov, R. A.; Silvestrov, G. I.; Skrinsky, A. N.; Soloviov, N. A.; Taskaev, S. Yu.

    The proton accelerator complex for neutron production in lithium target discussed, which can operate in two modes. The first provides a neutron beam kinematically collimated with good forward direction in 25° and average energy of 30 keV, directly applicable for neutron-capture therapy with high efficiency of proton beam use. The proton energy in this mode is 1.883-1.890 MeV that is near the threshold of the 7Li( p, n) 7Be reaction. In the second mode, at proton energy of 2.5 MeV, the complex-produced neutron beam with maximum energy board of 790 keV which can be used directly for fast neutron therapy and for neutron-capture therapy after moderation. The project of such a neutron source is based on the 2.5 MeV original electrostatic accelerator tandem with vacuum insulation developed at BINP which is supplied with a high-voltage rectifier. The rectifier is produced in BINP as a part of ELV-type industrial accelerator. Design features of the tandem determining its high reliability in operation with a high-current (up to 40 mA) H - ion beam are discussed. They are: the absence of ceramic accelerator columns around the beam passage region, good conditions for pumping out of charge-exchange gaseous target region, strong focusing optics and high acceleration rate minimizing the space charge effects. The possibility of stabilization of protons energy with an accuracy level of 0.1% necessary for operation in the near threshold region is considered. The design description of H - continuous ion source with a current of 40 mA is also performed. To operate with a 100 kW proton beam it is proposed to use liquid-lithium targets. A thin lithium layer on the surface of a tungsten disk cooled intensively by a liquid metal heat carrier is proposed for use in case of the vertical beam, and a flat liquid lithium jet flowing through the narrow nozzle - for the horizontal beam.

  13. Radiosensitivity of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction.

    OpenAIRE

    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

    [Objectives] To detect the radiosensitivity of intratumour quiescent (Q) cells unlabelled with pimonidazole to accelerated carbon ion beams and the boron neutron capture reaction (BNCR). [Methods] 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...

  14. Gadolinium-neutron capture reactions: A radiobiological assay

    International Nuclear Information System (INIS)

    Gadolinium neutron capture(GNC) takes advantage of its extraordinarily large cross section to thermal neutrons. In GNC reactions, prompt high energy gamma rays, x-rays and electrons are released. Because of the photons and electrons, the intracellular presence of gadolinium is not considered critical. This is an advantage over boron-neutron capture therapy where the intracellular presence of boron is required because of the short flight tracks of 2.4 MeV alpha particles. In this study, the radiation effect of GNC reactions was measured using Chinese hamster cells in an attempt to evaluate the contributions of neutrons, gamma rays and electrons on cell inactivation

  15. Synovectomy by Neutron capture

    International Nuclear Information System (INIS)

    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 Pu239 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)

  16. 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

  17. Role of the Tapiro Fast Research Reactor in Neutron Capture Therapy in Italy Calculations and Measurements

    International Nuclear Information System (INIS)

    Thermal-neutron research reactors are currently the most common source of neutron beams for both research and clinical trials of neutron capture therapy (NCT). Neutron spectra suitable for NCT are typically produced either by beam filtering or spectrum shifting techniques. However, fast-neutron reactors are also being considered for NCT application as it is recognized that they may allow for improved beam quality. TAPIRO is a low power, high flux, highly enriched (93.5% 235U) fast reactor. The power is 5 kW and the maximum neutron flux in the core is 3x1012 cm-2.s-1. Both a thermal and an epithermal column have been designed and constructed, aimed at dosimetry and animal experiments. The configurations of the columns have been designed by means of Monte Carlo calculations. The columns have been characterized by means of measurements performed with activation techniques and thermoluminescence and gel dosimeters. Experimental results have shown good consistency with calculations. Moreover, they have confirmed the good quality of the beams obtainable with such a reactor. An epithermal column for clinical trials of patients with brain gliomas has been designed and is under construction. The treatment planning figures-of-merit in an anthropomorphic phantom look very satisfactory. (author)

  18. Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan)], E-mail: fujitaku@hp.pref.hyogo.jp; Ichikawa, H. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Fujita, I. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Kishimoto, K.; Hara, H. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Kawamitsu, H. [Department of Radiology, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Sharma, P.; Brown, S.C.; Moudgil, B.M. [Particle Engineering Research Center, University of Florida, Gainesville, FL32611 (United States); Fujii, M. [Department of Radiology, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Yamamoto, T. [Department of Orthopaedic Surgery, Kagawa University, Kagawa 761-0793 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Fukumori, Y. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

    2009-07-15

    Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

  19. Comparison of doses delivered in clinical trials of neutron capture therapy in the USA

    International Nuclear Information System (INIS)

    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)

  20. DNA double-strand break induction in Ku80-deficient CHO cells following Boron Neutron Capture Reaction

    International Nuclear Information System (INIS)

    Boron neutron capture reaction (BNCR) is based on irradiation of tumors after accumulation of boron compound. 10B captures neutrons and produces an alpha (4He) particle and a recoiled lithium nucleus (7Li). These particles have the characteristics of high linear energy transfer (LET) radiation and have marked biological effects. The purpose of this study is to verify that BNCR will increase cell killing and slow disappearance of repair protein-related foci to a greater extent in DNA repair-deficient cells than in wild-type cells. Chinese hamster ovary (CHO-K1) cells and a DNA double-strand break (DSB) repair deficient mutant derivative, xrs-5 (Ku80 deficient CHO mutant cells), were irradiated by thermal neutrons. The quantity of DNA-DSBs following BNCR was evaluated by measuring the phosphorylation of histone protein H2AX (gamma-H2AX) and 53BP1 foci using immunofluorescence intensity. Two hours after neutron irradiation, the number of gamma-H2AX and 53BP1 foci in the CHO-K1 cells was decreased to 36.5-42.8% of the levels seen 30 min after irradiation. In contrast, two hours after irradiation, foci levels in the xrs-5 cells were 58.4-69.5% of those observed 30 min after irradiation. The number of gamma-H2AX foci in xrs-5 cells at 60-120 min after BNCT correlated with the cell killing effect of BNCR. However, in CHO-K1 cells, the RBE (relative biological effectiveness) estimated by the number of foci following BNCR was increased depending on the repair time and was not always correlated with the RBE of cytotoxicity. Mutant xrs-5 cells show extreme sensitivity to ionizing radiation, because xrs-5 cells lack functional Ku-protein. Our results suggest that the DNA-DSBs induced by BNCR were not well repaired in the Ku80 deficient cells. The RBE following BNCR of radio-sensitive mutant cells was not increased but was lower than that of radio-resistant cells. These results suggest that gamma-ray resistant cells have an advantage over gamma-ray sensitive cells in BNCR

  1. DNA double-strand break induction in Ku80-deficient CHO cells following Boron Neutron Capture Reaction

    Directory of Open Access Journals (Sweden)

    Masunaga Shinichiro

    2011-09-01

    Full Text Available Abstract Background Boron neutron capture reaction (BNCR is based on irradiation of tumors after accumulation of boron compound. 10B captures neutrons and produces an alpha (4He particle and a recoiled lithium nucleus (7Li. These particles have the characteristics of high linear energy transfer (LET radiation and have marked biological effects. The purpose of this study is to verify that BNCR will increase cell killing and slow disappearance of repair protein-related foci to a greater extent in DNA repair-deficient cells than in wild-type cells. Methods Chinese hamster ovary (CHO-K1 cells and a DNA double-strand break (DSB repair deficient mutant derivative, xrs-5 (Ku80 deficient CHO mutant cells, were irradiated by thermal neutrons. The quantity of DNA-DSBs following BNCR was evaluated by measuring the phosphorylation of histone protein H2AX (gamma-H2AX and 53BP1 foci using immunofluorescence intensity. Results Two hours after neutron irradiation, the number of gamma-H2AX and 53BP1 foci in the CHO-K1 cells was decreased to 36.5-42.8% of the levels seen 30 min after irradiation. In contrast, two hours after irradiation, foci levels in the xrs-5 cells were 58.4-69.5% of those observed 30 min after irradiation. The number of gamma-H2AX foci in xrs-5 cells at 60-120 min after BNCT correlated with the cell killing effect of BNCR. However, in CHO-K1 cells, the RBE (relative biological effectiveness estimated by the number of foci following BNCR was increased depending on the repair time and was not always correlated with the RBE of cytotoxicity. Conclusion Mutant xrs-5 cells show extreme sensitivity to ionizing radiation, because xrs-5 cells lack functional Ku-protein. Our results suggest that the DNA-DSBs induced by BNCR were not well repaired in the Ku80 deficient cells. The RBE following BNCR of radio-sensitive mutant cells was not increased but was lower than that of radio-resistant cells. These results suggest that gamma-ray resistant cells have

  2. About neutron capture therapy method development at WWR-SM reactor in institute of Nuclear Physics of Uzbekistan Academy of Sciences

    International Nuclear Information System (INIS)

    Full text: Neutron capture therapy (NCT) is developing method of swellings treatment, on which specialists set one's serious hopes, as at its realization the practical possibilities of the effect on any swellings open. The essence of method is simple and lies in the fact that to the swelling enter preparation containing boron or gadolinium, which one have a large capture cross-section of the thermal and slow neutrons. Then the swelling is irradiated once with the slow (epithermal) neutron beam with fluency about 109 neutrons /sm2s for a short time and single. As a result of thermal neutrons capture by the boron (or gadolinium) nuclei secondary radiation which affecting swelling cells is emitted. NCT of oncologic diseases makes the specific demands to physical parameters of neutron beams. Now research reactors are often used for NCT. However, research reactor WWR-SM (INP, Uzbekistan AS, Tashkent) doesn't provide with the epithermal neutron beams and to develop this technique the reactor, first of all, needs for obtaining the epithermal neutron beams with energy spectrum in range from 1 eV up to 10 keV and with intensity ∼ 109 neutron /sm2s. Practically it is connected with upgrade of at least one of existed reactor channels, namely with equipping with the special equipment (filters), forming from the reactor spectrum the beam of necessary energy neutrons. It requires realization of preliminary model calculations, including calculations of capture cross-sections, of filters types and their geometrical parameters on the basis of optimal selected materials. Such calculations, as a rule, are carried out on the basis of Monte-Carlo method and designed software for calculation of nuclear reactor physical and technical characteristics [1]. In this work the calculation results of devices variants and problems discussion, related with possibility of WWR-SM reactor using for NCT are presented. (author)

  3. 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.

  4. Nuclear research reactors medical applications. A novel neutron capture therapy for cancer

    International Nuclear Information System (INIS)

    TAOrMINA (Advanced Treatment Organs by Means of Neutron Irradiation and Autotransplant) is a novel application of BNCT dedicated to the therapy of cancer spread in human organs. In particular, TAOrMINA method can be applied to all organs that can be submitted to auto-transplant procedure. The therapeutic concept is based on the neutron irradiation of the organ removed from the patient, after being adequately perfused with a boron compound, and re-implanted in the patient after neutron treatment. The boron perfusion is accomplished by injecting a 10Bfructose solution for few hours. Soon after the organ is explanted and prepared for transport to the reactor facility where it is irradiated in a thermal neutron field. Due to the sensible higher concentration of boron in the cancer with respect to the normal tissue, during the treatment, the dose absorption in cancer cells is highly destructive while the healthy cells are preserved under the tolerance level (less than 15 Gy). In December 2001 the first patient, operated at the hospital 'S. Matteo' of Pavia, was treated at the 'L.E.N.A.' Centre of the University of Pavia where an irradiation facility of the TRIGA reactor (the Thermal Column) was redesigned and rearranged for the purpose of the treatment. The patient, suffering from more than 20 cancerous metastases into the liver, had an expectation of life of few weeks. His present-day conditions are the best expected: all the metastases have been completely destroyed and there are no more evidences of cancer in his liver. According to his words 'he is enjoying again a life of satisfactory quality'. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-09-01

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

  6. Exploratory calculations for boron capture therapy using epithermal neutron beams

    International Nuclear Information System (INIS)

    To get an insight into the problems of boron neutron capture therapy of brain tumours, some calculations of the neutron distribution in a spherical human skull have been made with an ANISN program. The energy of the source neutrons was varied from about 1 keV to about 100 keV. Two different neutron group structures were used with corresponding different cross section libraries. For a spherically symmetric irradiation of a skull with radius 10 cm a source neutron energy of about 50 - 100 keV gives a rather flat boron capture rate over a large part of the skull. This shows the advantage of using epithermal neutrons in the treatment of deepseated tumours by the boron neutron capture method. (Auth.)

  7. Design and preparation of ethyl cellulose microcapsules of gadopentetate dimeglumine for neutron-capture therapy using the Wurster process.

    Science.gov (United States)

    Fukumori, Y; Ichikawa, H; Tokumitsu, H; Miyamoto, M; Jono, K; Kanamori, R; Akine, Y; Tokita, N

    1993-06-01

    Microcapsules of hygroscopic, highly water-soluble gadopentetate dimeglumine (Gd-DTPA-DM) for use in preliminary in vivo experiments for neutron-capture therapy were designed. They were prepared with such properties as a particle size small enough to be suspended and injected through a syringe, a negligible release of Gd-DTPA-DM, and a high drug content by means of the Wurster process, a spray coating method using a spouted bed with a draft tube. They were composed of lactose cores of 53-63 microm, an undercoat of ethyl cellulose (EC) and polyvinylpyrrolidone (PVP), a drug-layer of Gd-DTPA-DM, EC and PVP, a waterproof coat and a release-sustaining overcoat of EC and cholesterol (1:1), and a surface treated with hydrogenated egg lecithin. By curing at 110 degrees C for 30 min after mixing with 20% pulverized mannitol powder, the 20% overcoating suppressed the release of Gd-DTPA-DM from 75-106 microm microcapsules to less than 10% for the first 20 min, which was the period required to prepare a suspension, inject it and irradiate the neutron. The microcapsules could be used to confirm that the intracellular presence of Gd is not critical in gadolinium neutron-capture therapy. PMID:8370113

  8. 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.

  9. 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)

    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

  10. Boron cures cancer

    International Nuclear Information System (INIS)

    In this work the authors cite a few examples of the use of radiopharmaceuticals for diagnostic and therapeutic purposes in nuclear medicine. They point to the possibility of boron neutron capture therapy and the use for the neutron capture therapy of other light elements.

  11. Development and in vitro testing of liposomal gadolinium-formulations for neutron capture therapy of glioblastoma multiforme

    International Nuclear Information System (INIS)

    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.

  12. Evaluation of depth-dose distributions for gadolinium neutron capture therapy

    International Nuclear Information System (INIS)

    The radiation effect of gadolinium neutron capture reaction in cultured Chinese hamster cells was reported before. The comparison of the results at 10% survival level between the cell cultures with and without gadolinium showed 3.5-fold difference in the neutron fluence. In this paper, total depth dose distribution is calculated for a cylindrical phantom with a simulated tumor containing gadolinium. The distributions of neutron and capture gamma-ray fluxes were calculated by using the two-dimensional coupled neutron-photon transport code. The coupled neutron-photon cross section used for the calculation was based on the vitamin C library. The prompt gamma-ray and internal conversion electron spectra of 157Gd(n,γ) reaction were taken from published data. The model was a R-Z geometry water phantom. A cylindrical tumor was placed near the surface. The thermal neutron beam of the Musashi reactor was used. The absorbed dose rates of neutrons and capture gamma-ray were calculated. The notable reduction of thermal neutron flux was observed across the simulated tumor, while the capture gamma-ray dose rate increased. (K.I.)

  13. 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.

  14. Neutron capture therapy clinical development in the world%中子俘获疗法临床应用国际进展

    Institute of Scientific and Technical Information of China (English)

    张紫竹; 金从军; 刘凯; 张国珍; 杨立军

    2012-01-01

    硼中子俘获疗法(BNCT)目前在国际上已经临床应用于千余例患者,并取得了较好的治疗效果.主要对BNCT的原理、发展历史及国际BNCT临床进展情况作了主要介绍.对脑胶质瘤、恶性黑色素瘤、复发性头颈部肿瘤及转移性肝癌BNCT临床治疗情况及治疗效果作了较详细的讨论.%Boron neutron capture therapy (BNCT) method was applied to about one thousand clinical patients and achieved good results internationally. In this paper, the principle of BNCT, the development history and international BNCT clinical progress were mainly introduced. The BNCT clinical treatment situation and evaluation in glioblastoma (GBM) , malignant melanoma, recurrent head and neck cancer and metastatic liver cancer were discussed in detail.

  15. Development of a method to extend by boron neutron capture process the therapeutic possibilities of a liver autograft

    Science.gov (United States)

    Pinelli, Tazio; Altieri, Saverio; Fossati, F.; Zonta, Aris; Prati, U.; Roveda, L.; Nano, Rosanna

    1997-02-01

    We present results on surgical technique, neutron filed and irradiation facility concerning the original treatment of the liver diffused metastases. Our method plans to irradiate the isolated organ at a thermal neutron field soon after having been explanted and boron enriched and before being grafted into the same donor. In particular the crucial point of boron uptake was investigated by a rat model with a relevant number of procedure. We give for the first time statistically significant results on the selective boron absorption by tumor tissues.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-06-01

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

  17. Neutron Capture Nucleosynthesis

    OpenAIRE

    Kiss, Miklos

    2016-01-01

    Heavy elements (beyond iron) are formed in neutron capture nucleosynthesis processes. We have proposed a simple unified model to investigate the neutron capture nucleosynthesis in arbitrary neutron density environment. We have also investigated what neutron density is required to reproduce the measured abundance of nuclei assuming equilibrium processes. We found both of these that the medium neutron density has a particularly important role at neutron capture nucleosynthesis. About these resu...

  18. Neutron Capture Nucleosynthesis

    CERN Document Server

    Kiss, Miklos

    2016-01-01

    Heavy elements (beyond iron) are formed in neutron capture nucleosynthesis processes. We have proposed a simple unified model to investigate the neutron capture nucleosynthesis in arbitrary neutron density environment. We have also investigated what neutron density is required to reproduce the measured abundance of nuclei assuming equilibrium processes. We found both of these that the medium neutron density has a particularly important role at neutron capture nucleosynthesis. About these results most of the nuclei can formed at medium neutron capture density environment e.g. in some kind of AGB stars. Besides these observations our model is capable to use educational purpose.

  19. Design and preparation of gadolinium-reservoir microcapsules for neutron-capture therapy by means of the Wurster process.

    Science.gov (United States)

    Miyamoto, M; Ichikawa, H; Fukumori, Y; Akine, Y; Tokuuye, K

    1997-12-01

    Gadolinium (Gd)-containing microcapsules designed for neutron-capture therapy (NCT) were prepared by a spouted bed coating process. Microcapsules were designed as a Gd-reservoir. They were prepared with the following properties: particle size was smaller than 50 microns, Gd-content was as high as possible, and release of Gd was suppressed as long as possible. Calcium carbonate (20-32 microns) was selected as a speed particle. As a Gd-source, gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) or a synthesized water-insoluble Gd-DTPA derivative, Gd-DTPA-distearylamide (Gd-DTPA-SA), was layered onto the seed particles. The release-suppressing layer was composed of aqueous acrylic latex of 9:9:4 poly(ethyl acrylate/methyl methacrylate/2-hydroxyethyl methacrylate). In preliminary studies, Gd-DTPA microcapsules with 41-45 microns (mass median diameter) were prepared; they released Gd with a short lag-time and 3h-prolongation. Complete release suppression was, however, difficult to achieve because of high water-solubility of Gd-DTPA. Hence, a hydrophobic derivative, Gd-DTPA-SA, was next used as a Gd source. Gd-DTPA-SA microcapsules could be prepared with a mass median diameter of 52 microns. Gd-DTPA-SA content of the microcapsules was 38% and release of Gd was suppressed to less than 0.2% over 60 d. PMID:9433776

  20. Thermal neutron capture therapy: The Japanese-Australian clinical trial for malignant melanoma

    International Nuclear Information System (INIS)

    Following the first NCT treatment for melanoma last year in Japan, it is planned to treat at least 12 patients during 1988, from Australia and Japan. Patients will be selected from those having evaluable superficial or subcutaneous local recurrence or isolated metastasis. In addition, selected Japanese patients with thick primary acral-lentiginous melanoma or superficially spreading melanoma that have poor prognosis with conventional therapy will be treated with NCT. Australian patients will be selected from those attending the Sydney Melanoma Unit at Royal Prince Alfred Hospital. They will have no detectable deep-seated distant metastases and should have an estimated life expectancy of at least 6 months. Locally recurrent or advanced melanoma are rare conditions, thanks to the increased awareness of the public and general practitioners and to the more stringent procedures adopted by surgeons

  1. To development of neutron-capture therapy method with using WWR-SM nuclear research reactor of Institute of Nuclear Physics

    International Nuclear Information System (INIS)

    The possibility of application of Uz AS INP WWR-SM nuclear research reactor for development of neutron capture therapy method of human cancer is discussed. The reconstruction necessity of the available horizontal channel in order to receive the neutron flux with required intensity and spectrum is shown. With this purpose the calculations of reactor neutron transport through filter materials forming epithermal neutron beam on channel exit are carried out, and components and geometry of filters materials for practical making are recommended. (authors)

  2. Quantitative analysis of proton boron fusion therapy (PBFT) in various conditions

    International Nuclear Information System (INIS)

    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)

  3. 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)

  4. Neutron capture therapy of intracerebral melanoma: enhanced survival and cure after blood-brain barrier opening to improve delivery of boronophenylalanine

    International Nuclear Information System (INIS)

    Purpose: Multicentric cerebral metastases of melanoma represent an important clinical problem for which there currently is no satisfactory treatment. We previously developed a model for melanoma metastatic to the brain employing nude rats bearing intracerebral implants of the human MRA27 melanoma. The purpose of the present study was to determine if the efficacy of boron neutron capture therapy (BNCT) could be improved by either Cereport (RMP-7) mediated modulation of blood-brain barrier (BBB) permeability or hyperosmotic mannitol-induced BBB disruption using boronophenylalanine (BPA) as the capture agent. Methods and Materials: Biodistribution studies were carried out at 0.5, 2.5, and 4 h after intracarotid administration of Cereport (1.5 μg/kg) and intracarotid or i.v. administration of BPA (500 mg/kg). Peak tumor boron concentrations (65.4 μg/g) and the best composite tumor:brain (6.1:1) and tumor:blood (6.3:1) ratios were observed at 2.5 h after intracarotid administration. BNCT was initiated at the Brookhaven Medical Research Reactor 13-14 days after intracerebral implantation of 106 MRA27 cells. Results: Untreated control rats had a median survival time (MeST) of 22 days and for irradiated controls, it was 30 days. Rats that received i.v. or intracarotid BPA without Cereport followed by BNCT 2.5 h later had MeSTs of 41 days and 57 days, respectively, with 20% long-term survivors (>180 days) in the latter group. Rats that received intracarotid BPA with Cereport had an MeST of 86 days with 36% long-term survivors, which was very close to that of rats that had hyperosmotic mannitol-induced disruption of the BBB (85 days with 25% long-term survivors). When these two groups were combined, and survival times were compared, using the Wilcoxon rank sum test, to those of rats that received intracarotid BPA without blood-brain barrier disruption, these differences were significant at the level p=0.01. Conclusions: Our data show that optimizing the delivery of BPA by

  5. PARP inhibitor 3-aminobenzamide does not increase the yields of chromosomal aberrant cells induced by boron neutron capture reaction in V79 Chinese hamster cells

    International Nuclear Information System (INIS)

    Full text: Mechanistic knowledge on DNA and cell damage induced by alpha-particles remains limited. It is well known that high-LET radiation induces both DNA single (ssb) and double strand breaks (dsb), being the latter frequently associated with cell death. The repair of these DNA lesions and specially dsb are thus fundamental for the understanding of high-LET radiation effects. Poly (ADP-ribose) polymerase is a nuclear enzyme, which detects and signals DNA strand breaks (ssb and dsb). The important role of this enzyme in the maintenance of DNA integrity has been extensively studied for genotoxic chemicals and low-LET ionizing radiation. Nevertheless, sparse information concerning the role of PARP in high-LET radiation effects is available. The purpose of this work is to examine whether the PARP inhibitor 3-aminobenzamide (3-AB) enhances the yields of chromosomal aberrations induced by the boron neutron capture (BNC) reaction in V79 Chinese hamster cells. Wild-type V79 cells were pre-incubated for 48 hours with different concentrations (0.48-2.4 mM) of the boron delivery agent 4-borono-L-phenylalanine (BPA) and then irradiated for different periods of time with thermal neutrons. In the 3-AB treated cultures, four hours before the irradiation the cells were incubated with different concentrations of this inhibitor (1.5-10 mM) which remained in culture until colchicine was added. The chromosomal aberrations assay was performed according to standard protocol. A clear dose-response in the frequencies of chromosomal aberrant cells excluding gaps (%CAEG) induced by the BNC reaction was observed for both BPA concentration and thermal neutron fluence. There was no evidence of an increase in the % CAEG induced after incubation with 3-AB. Some cytoxicity was observed (mitotic index) after 3-AB incubation in BPA irradiated cells. In conclusion, the clastogenic potential of the alpha-particles generated through the BNC reaction was not affected by using a classic PARP

  6. Neutron capture radiography to determine the concentration of natural boron in leaves using the nuclear reaction 10B(n,α)7Li

    International Nuclear Information System (INIS)

    Neutron capture radiography (NCR) is a nuclear analytical imaging method. It is based on using thermal neutron induced nuclear reactions, such as (n,p), (n,α) or (n,f). Clearly NCR can be used for the detection of only those nuclides whose cross-section (σ) for one of these nuclear reactions is not too low. With σ being indicated in barns (1 barn 10-28m2) in brackets, this is the case especially with 14N (1.83), 35Cl (0.48), 40K (4.4) for (n,p) reactions; 6Li (941.4), 10B (3836), 17O (0.24), 35S (0.14), 40K (0.39) for (n,α) reactions; and 235U (583) and 239Pu (742) for neutron induced fissions (n,f). Some of these nuclear reactions are characteristic of stable isotopes (14N, 6Li, 10B, 17O) of chemical elements that are highly relevant for biology but have no radioactive isotope usable in practice. It is possible to use these stable isotopes for the labelling and analytical imaging of the corresponding elements almost as easily as with radioactive tracers when they exist. Some of these nuclear reactions are characteristic of stable isotopes (14N, 6Li, 10B, 17O) of chemical elements that are highly relevant for biology but have no radioactive isotope usable in practice. It is possible to use these stable isotopes for the labelling and analytical imaging of the corresponding elements almost as easily as with radioactive tracers when they exist. In conventional NCR studies, the biological specimen (a histological section in most cases) is laid against an appropriate detector (most often a film of cellulose nitrate or polycarbonate), and then this whole assembly is irradiated with thermal neutrons. The impact of the ionizing particles (p,α, fission fragments) emitted by the nuclear reactions creates latent tracks in the detecting film. Using an appropriate chemical treatment (most often by dipping the detectors in a strong alkaline solution), the latent tracks are enlarged to the size of tracks visible with an optical microscope. The features (especially the size

  7. In vivo evaluation of the 3-carboranyl thymidine analogue (3-CTA), N5-2OH, for neutron capture therapy

    International Nuclear Information System (INIS)

    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. 10B-enriched N5-2OH, solubilized in DMSO (50μg 10B 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 mm3). 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 103 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)

  8. On adaptation of the WWR-K reactor horizontal channel to the neutron-capture therapy tasks

    International Nuclear Information System (INIS)

    Full text: At the Institute of Nuclear Physics of the National Nuclear Center of the Republic of Kazakhstan water-water research reactor the studies related to adaptation of one of the reactor horizontal channel to treatment of malignant tumors by techniques of neutron-capture therapy (NCT) are carried out for several years. The studies are implemented in the frame of the republican research program 'Development of Nuclear Power in Kazakhstan'. The need in NCT in Kazakhstan is rather urgent, because the number of people suffered from cancer diseases is large. The NCT technique is widely used over the world but in special medical reactors. An idea of utilization of the research nuclear reactor for medical purposes seems to be rather attractive, because in this case financial expenditures will be considerably lower. In view of NCT, the reactor horizontal channel GK-1, transporting the neutron beam from the reactor core via the biological shield to the reactor hall, was chosen. Evaluation of the neutronic parameters of the neutron beam along the channel length and the channel exit was performed with/without the lead neutron guide installed in the reactor core, in order to increase the neutron flux density at the channel exit and to reduce the photon component of the beam. Before in-reactor experiments, the appropriate calculations by means of special computer codes and the modeling experiments at the critical assembly were performed. As a whole, the following has been done in the frame of the studies in question: the distributions of the thermal/fast neutron flux density over the length of the horizontal channel have been measured with/without the neutron guide at various levels of the reactor power; the corresponding indices (cadmium ratios) have been found; it has been found that the lead-made neutron guide, installed in the reactor core, doubles the thermal neutron flux density at the beam exit from the channel; the gamma-radiation dose rates in the channel and in

  9. 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

  10. 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.

  11. Calculations of neutron source at the KYIV research reactor for the boron neutron capture therapy aims

    International Nuclear Information System (INIS)

    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

  12. Boron neutron capture therapy (BNCT) selectively destroys human clear cell sarcoma in mouse model

    International Nuclear Information System (INIS)

    Clear cell sarcoma of tendons and aponeuroses (CCS) is a rare malignant tumor with no effective treatment. This study demonstrates the efficacy of BNCT with the use of human CCS-bearing nude mice. Groups A and C were administered saline, and groups B and D were injected with p-borono-L-phenylalanine-fructose complex. Groups C and D were then irradiated with thermal neutrons. The tumors in only group D disappeared, demonstrating that BNCT is a potentially new option for the treatment of human CCS. - Highlights: ► Human clear cell sarcoma (CCS)-bearing nude mice were used in this study. ► The human CCS in the nude mice disappeared after BNCT. ► The efficacy of BNCT for human CCS is demonstrated here for the first time

  13. Biological dosimetry studies for boron neutron capture therapy at the RA-1 research reactor facility

    International Nuclear Information System (INIS)

    Initial physical dosimetry measurements have been completed using activation spectrometry and thermoluminescent dosimeters to characterize the BNCT facility developed at the RA-1 research reactor operated by the National Atomic Energy Commission in Buenos Aires. Biological dosimetry was performed employing the hamster cheek pouch oral cancer model previously validated for BNCT studies by our group. Results indicate that the RA-1 neutron source produces useful dose rates for BNCT studies but that some improvements in the initial configuration will be needed to optimize the spectrum for thermal-neutron BNCT research applications. (author)

  14. 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

    years ago, where patients with liver metastases were treated successfully by combining BNCT with auto-transplantation of the organ. Here, in Mainz, a preclinical trial has been started on patients suffering from liver metastases of colorectal carcinoma. In vitro experiments and the first animal tests...... 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....

  15. Boron neutron capture therapy for the treatment of oral cancer in the hamster cheek pouch model

    International Nuclear Information System (INIS)

    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. 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)

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

    International Nuclear Information System (INIS)

    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

  18. Boron neutron capture therapy for an explanted organ: The logistical challenges

    Energy Technology Data Exchange (ETDEWEB)

    Wittig, A. [Department of Radiation Oncology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, Essen (Germany)], E-mail: andrea.wittig@uni-due.de; Moss, R. [HFR Unit, Institute for Energy, Joint Research Centre, European Commission, Westerduinweg 3, Petten (Netherlands); Kaiser, G.M. [Department of General-, Visceral- and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, Essen (Germany); Malago, M. [Department of Surgery-UCL Division of Surgical and Interventional Sciences, University College London-University of London, 74 Huntley Street, London (United Kingdom); Nievaart, V. [HFR Unit, Institute for Energy, Joint Research Centre, European Commission, Westerduinweg 3, Petten (Netherlands); Sauerwein, W.A. [Department of Radiation Oncology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, Essen (Germany)

    2009-07-15

    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.