Boron neutron capture therapy combined with fractionated photon irradiation for glioblastoma: A recursive partitioning analysis of BNCT patients

International Nuclear Information System (INIS)

Nakai, K.; Yamamoto, T.; Aiyama, H.; Takada, T.; Yoshida, F.; Kageji, T.; Kumada, H.; Isobe, T.; Endo, K.; Matsuda, M.; Tsurubuchi, T.; Shibata, Y.; Takano, S.; Mizumoto, M.; Tsuboi, K.; Matsumura, A.

2011-01-01

Eight patients to received Boron Neutron Capture Therapy (BNCT) were selected from 33 newly diagnosed glioblastoma patients (NCT(+) group). Serial 42 glioblastoma patients (NCT(−) group) were treated without BNCT. The median OS of the NCT(+) group and NCT (−) group were 24.4 months and 14.9 months. In the high risk patients (RPA class V), the median OS of the NCT(+) group tended to be better than that of NCT(−) group. 50% of BNCT patients were RPA class V. - Highlights: ► We treated 8 patients with boron neutron capture therapy (NCT) for glioblastoma. ► We compare the overall survival between NCT including series and without NCT series. ► The median overall survival of the NCT including series was 24.4 months. ► In the high risk patients, the median OS of NCT including series tended to be better.

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

International Nuclear Information System (INIS)

Dorn, R.V. III.

1989-06-01

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

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.

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)

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

International Nuclear Information System (INIS)

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

1991-01-01

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

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

International Nuclear Information System (INIS)

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

2005-01-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

In the present study we evaluated the therapeutic effect and/or potential radiotoxicity of the novel 'Tandem' Boron Neutron Capture Therapy (T-BNCT) for the treatment of oral cancer in the hamster cheek pouch model at RA-3 Nuclear Reactor. Two groups of animals were treated with 'Tandem BNCT', i.e. BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (T-24h-BNCT) or 48 h (T-48h-BNCT) later. A total tumor dose-matched single application of BNCT mediated by BPA and GB-10 administered jointly ((BPA + GB-10)-BNCT) was administered to an additional group of animals. At 28 days post-treatment, T-24h-BNCT and T-48h-BNCT induced, respectively, overall tumor control (OTC) of 95% and 91%, with no statistically significant differences between protocols. Tumor response for the single application of (BPA + GB-10)-BNCT was 75%, significantly lower than for T-BNCT. The T-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47% and 60% of the animals respectively. No normal tissue radiotoxicity was associated to tumor control for any of the protocols. 'Tandem' BNCT enhances tumor control in oral cancer and reduces or, at worst, does not increase, mucositis in dose-limiting precancerous tissue.

An Accelerator Neutron Source for BNCT

Energy Technology Data Exchange (ETDEWEB)

Blue, Thomas, E

2006-03-14

The overall goal of this project was to develop an accelerator-based neutron source (ABNS) for Boron Neutron Capture Therapy (BNCT). Specifically, our goals were to design, and confirm by measurement, a target assembly and a moderator assembly that would fulfill the design requirements of the ABNS. These design requirements were 1) that the neutron field quality be as good as the neutron field quality for the reactor-based neutron sources for BNCT, 2) that the patient treatment time be reasonable, 3) that the proton current required to treat patients in reasonable times be technologially achievable at reasonable cost with good reliability, and accelerator space requirements which can be met in a hospital, and finally 4) that the treatment be safe for the patients.

An Accelerator Neutron Source for BNCT

International Nuclear Information System (INIS)

Blue, Thomas E.

2006-01-01

The overall goal of this project was to develop an accelerator-based neutron source (ABNS) for Boron Neutron Capture Therapy (BNCT). Specifically, our goals were to design, and confirm by measurement, a target assembly and a moderator assembly that would fulfill the design requirements of the ABNS. These design requirements were (1) that the neutron field quality be as good as the neutron field quality for the reactor-based neutron sources for BNCT, (2) that the patient treatment time be reasonable, (3) that the proton current required to treat patients in reasonable times be technologically achievable at reasonable cost with good reliability, and accelerator space requirements which can be met in a hospital, and finally (4) that the treatment be safe for the patients

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

International Nuclear Information System (INIS)

Yamamoto, T.; Matsumura, A.; Nose, T.; Shibata, Y.; Nakai, K.; Sakurai, F.; Kishi, T.; Kumada, H.; Yamamoto, K.; Torii, Y.

2001-01-01

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)

Subcellular boron and fluorine distributions with SIMS ion microscopy in BNCT and cancer research

Energy Technology Data Exchange (ETDEWEB)

Subhash Chandra

2008-05-30

The development of a secondary ion mass spectrometry (SIMS) based technique of Ion Microscopy in boron neutron capture therapy (BNCT) was the main goal of this project, so that one can study the subcellular location of boron-10 atoms and their partitioning between the normal and cancerous tissue. This information is fundamental for the screening of boronated drugs appropriate for neutron capture therapy of cancer. Our studies at Cornell concentrated mainly on studies of glioblastoma multiforme (GBM). The early years of the grant were dedicated to the development of cryogenic methods and correlative microscopic approaches so that a reliable subcellular analysis of boron-10 atoms can be made with SIMS. In later years SIMS was applied to animal models and human tissues of GBM for studying the efficacy of potential boronated agents in BNCT. Under this grant the SIMS program at Cornell attained a new level of excellence and collaborative SIMS studies were published with leading BNCT researchers in the U.S.

Subcellular boron and fluorine distributions with SIMS ion microscopy in BNCT and cancer research

International Nuclear Information System (INIS)

Subhash, Chandra

2008-01-01

The development of a secondary ion mass spectrometry (SIMS) based technique of Ion Microscopy in boron neutron capture therapy (BNCT) was the main goal of this project, so that one can study the subcellular location of boron-10 atoms and their partitioning between the normal and cancerous tissue. This information is fundamental for the screening of boronated drugs appropriate for neutron capture therapy of cancer. Our studies at Cornell concentrated mainly on studies of glioblastoma multiforme (GBM). The early years of the grant were dedicated to the development of cryogenic methods and correlative microscopic approaches so that a reliable subcellular analysis of boron-10 atoms can be made with SIMS. In later years SIMS was applied to animal models and human tissues of GBM for studying the efficacy of potential boronated agents in BNCT. Under this grant the SIMS program at Cornell attained a new level of excellence and collaborative SIMS studies were published with leading BNCT researchers in the U.S.

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

International Nuclear Information System (INIS)

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

1996-01-01

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

Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases

Energy Technology Data Exchange (ETDEWEB)

Bakeine, G.J. [Department of Clinical Medicine and Neurology, Cattinara Hospital, University of Trieste (Italy)], E-mail: jamesbakeine1@yahoo.com; Di Salvo, M. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, 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, University of Pavia, Via Bassi 6, Pavia (Italy); Bertolotti, A.; Nano, R. [Department of Animal Biology University of Pavia, Piazza Botta, Pavia (Italy); Clerici, A.; Ferrari, C.; Zonta, C. [Department of Surgery University of Pavia, Piazza Botta, Pavia (Italy); Marchetti, A. [Scientific Research Office, Fondazione San Matteo University Policlinic, Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi 6, Pavia (Italy)

2009-07-15

In order for boron neutron capture therapy (BNCT) to be eligible for application in lung tumour disease, three fundamental criteria must be fulfilled: there must be selective uptake of boron in the tumour cells with respect to surrounding healthy tissue, biological effectiveness of the radiation therapy and minimal damage or collateral effects of the irradiation on the surrounding tissues. In this study, we evaluated the biological effectiveness of BNCT by in vitro irradiation of rat colon-carcinoma cells previously incubated in boron-enriched medium. One part of these cells was re-cultured in vitro while the other was inoculated via the inferior vena cava to induce pulmonary metastases in a rat model. We observed a post-irradiation in vitro cell viability of 0.05% after 8 days of cell culture. At 4 months follow-up, all animal subjects in the treatment group that received irradiated boron-containing cells were alive. No animal survived beyond 1 month in the control group that received non-treated cells (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has a significant lethal effect on tumour cells and post irradiation surviving cells lose their malignant capabilities in vivo. This radio-therapeutic potential warrants the investigation of in vivo BNCT for lung tumour metastases.

Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases

International Nuclear Information System (INIS)

Bakeine, G.J.; Di Salvo, M.; Bortolussi, S.; Stella, S.; Bruschi, P.; Bertolotti, A.; Nano, R.; Clerici, A.; Ferrari, C.; Zonta, C.; Marchetti, A.; Altieri, S.

2009-01-01

In order for boron neutron capture therapy (BNCT) to be eligible for application in lung tumour disease, three fundamental criteria must be fulfilled: there must be selective uptake of boron in the tumour cells with respect to surrounding healthy tissue, biological effectiveness of the radiation therapy and minimal damage or collateral effects of the irradiation on the surrounding tissues. In this study, we evaluated the biological effectiveness of BNCT by in vitro irradiation of rat colon-carcinoma cells previously incubated in boron-enriched medium. One part of these cells was re-cultured in vitro while the other was inoculated via the inferior vena cava to induce pulmonary metastases in a rat model. We observed a post-irradiation in vitro cell viability of 0.05% after 8 days of cell culture. At 4 months follow-up, all animal subjects in the treatment group that received irradiated boron-containing cells were alive. No animal survived beyond 1 month in the control group that received non-treated cells (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has a significant lethal effect on tumour cells and post irradiation surviving cells lose their malignant capabilities in vivo. This radio-therapeutic potential warrants the investigation of in vivo BNCT for lung tumour metastases.

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

International Nuclear Information System (INIS)

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

2000-01-01

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

Microdosimetry for Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Maughan, R.L.; Kota, C.

2000-01-01

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

“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.

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

International Nuclear Information System (INIS)

Kreiner, A.J.; Thatar Vento, V.; Levinas, P.; Bergueiro, J.; Burlon, A.A.; Di Paolo, H.; Kesque, J.M.; Valda, A.A.; Debray, M.E.; Somacal, H.R.; Minsky, D.M.; Estrada, L.; Hazarabedian, A.; Johann, F.; Suarez Sandin, J.C.; Castell, W.; Davidson, J.; Davidson, M.; Repetto, M.; Obligado, M.; Nery, J.P.; Huck, H.; Igarzabal, M.; Fernandez Salares, A.

2008-01-01

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 7 Li(p,n) 7 Be 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 7 Li(p,n) 7 Be 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

Commissioning of accelerator based boron neutron capture therapy system

International Nuclear Information System (INIS)

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

2017-01-01

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

Boron-containing thioureas for neutron capture therapy

International Nuclear Information System (INIS)

Ketz, H.

1993-01-01

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

Boron neutron capture therapy (BNCT). Recent aspect, a change from thermal neutron to epithermal neutron beam and a new protocol

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu

1999-01-01

Since 1968, One-hundred seventy three patients with glioblastoma (n=81), anaplastic astrocytoma (n=44), low grade astrocytoma (n=16) or other types of tumor (n=32) were treated by boron-neutron capture therapy (BNCT) using a combination of thermal neutron and BSH in 5 reactors (HTR n=13, JRR-3 n=1, MuITR n=98, KUR n=28, JRR-2 n=33). Out of 101 patients with glioma treated by BNCT under the recent protocol, 33 (10 glioblastoma, 14 anaplastic astrocytoma, 9 low grade astrocytoma) patients lived or have lived longer than 3 years. Nine of these 33 lived or have lived longer than 10 years. According to the retrospective analysis, the important factors related to the clinical results were tumor dose radiation dose and maximum radiation dose in thermal brain cortex. The result was not satisfied as it was expected. Then, we decided to introduce mixed beams which contain thermal neutron and epithermal neutron beams. KUR was reconstructed in 1996 and developed to be available to use mixed beams. Following the shutdown of the JRR-2, JRR-4 was renewed for medical use in 1998. Both reactors have capacity to yield thermal neutron beam, epithermal neutron beam and mixed beams. The development of the neutron source lead us to make a new protocol. (author)

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Characterisation of an accelerator-based neutron source for BNCT versus beam energy

CERN Document Server

Agosteo, S; D'Errico, F; Nath, R; Tinti, R

2002-01-01

Neutron capture in sup 1 sup 0 B produces energetic alpha particles that have a high linear energy transfer in tissue. This results in higher cell killing and a higher relative biological effectiveness compared to photons. Using suitably designed boron compounds which preferentially localize in cancerous cells instead of healthy tissues, boron neutron capture therapy (BNCT) has the potential of providing a higher tumor cure rate within minimal toxicity to normal tissues. This clinical approach requires a thermal neutron source, generally a nuclear reactor, with a fluence rate sufficient to deliver tumorcidal doses within a reasonable treatment time (minutes). Thermal neutrons do not penetrate deeply in tissue, therefore BNCT is limited to lesions which are either superficial or otherwise accessible. In this work, we investigate the feasibility of an accelerator-based thermal neutron source for the BNCT of skin melanomas. The source was designed via MCNP Monte Carlo simulations of the thermalization of a fast ...

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Proceedings of neutron irradiation technical meeting on BNCT

International Nuclear Information System (INIS)

2000-10-01

The 'Neutron Irradiation Technical Meeting for Boron Neutron Capture Therapy (BNCT)' was held on March 13, 2000 at Tokai Research Establishment. The Meeting is aimed to introduce the neutron beam facility for medical irradiation at JRR-4 to Japanese researchers widely, as well as providing an opportunity for young researchers, engineers, medical representatives such surgeons and doctors of pharmacology to present their research activities and to exchange valuable information. JAERI researcher presented the performance and the irradiation technology in the JRR-4 neutron beam facility, while external researchers made various and beneficial presentations containing such accelerator-based BNCT, spectrum-shifter, biological effect, pharmacological development and so on. In this meeting, a special lecture titled 'The Dawn of BNCT and Its Development.' was given by MD, Prof. Takashi Minobe, an executive director of Japan Foundation for Emergency Medicine. The 11 of the presented papers are indexed individually. (J.P.N.)

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.

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)

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.

2009-01-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Proceedings of neutron irradiation technical meeting on BNCT

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-10-01

The 'Neutron Irradiation Technical Meeting for Boron Neutron Capture Therapy (BNCT)' was held on March 13, 2000 at Tokai Research Establishment. The Meeting is aimed to introduce the neutron beam facility for medical irradiation at JRR-4 to Japanese researchers widely, as well as providing an opportunity for young researchers, engineers, medical representatives such surgeons and doctors of pharmacology to present their research activities and to exchange valuable information. JAERI researcher presented the performance and the irradiation technology in the JRR-4 neutron beam facility, while external researchers made various and beneficial presentations containing such accelerator-based BNCT, spectrum-shifter, biological effect, pharmacological development and so on. In this meeting, a special lecture titled 'The Dawn of BNCT and Its Development.' was given by MD, Prof. Takashi Minobe, an executive director of Japan Foundation for Emergency Medicine. The 11 of the presented papers are indexed individually. (J.P.N.)

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

Science.gov (United States)

Musacchio González, Elizabeth; Martín Hernández, Guido

2017-09-01

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

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

Ultrastructural changes in tumor cells following boron neutron capture therapy

International Nuclear Information System (INIS)

Barkla, D.H.; Brown, J.K.; Meriaty, H.; Allen, B.J.

1992-01-01

In a previous study the authors reported on morphological changes in two human melanoma cell lines treated with 10 B-phenylalanine(BPA) and Boron Neutron Capture Therapy(BNCT). The present study describes morphological changes in melanoma and glioma cell lines treated with boron-tetraphenyl porphyrin(BTPP) and BNCT. Porphyrin compounds are selectively taken up by tumor cells and have been used clinically in phototherapy treatment of cancer patients. Boronated porphyrins show good potential as therapeutic agents in BNCT treatment of human cancer patients

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-03-01

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

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

International Nuclear Information System (INIS)

Takagaki, Masao; Ono, Koji; Masunaga, Shinichiro; Kinashi, Yuko; Kobayashi, Toru; Oda, Yoshifumi; Kikuchi, Haruhiko; Spielvogel, B.F.

1994-01-01

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 12 nvt for BMGP and 2x10 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 α-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)

Biodistribution, toxicity and efficacy of a boronated porphyrin for boron neutron capture therapy

International Nuclear Information System (INIS)

Miura, Michiko; Micca, P.; Fairchild, R.; Slatkin, D.; Gabel, D.

1992-01-01

Boron-containing porphyrins may be useful for boron neutron capture therapy (BNCT) in the treatment of brain tumors. Porphyrins have been shown to accumulate in tumor tissue and to be essentially excluded from normal brain. However, problems of toxicity may prevent some boron-containing porphyrins from being considered for BNCT. The authors have synthesized the boronated porphyrin 2,4-bis-vinyl-o-nidocarboranyl-deuteroporphyrin IX (VCDP). Preliminary studies in tumor-bearing mice showed considerable uptake of boron at a total dose of 150 μg/gbw with low mortality. They now report that a total dose to mice of ∼ 275 μg VCDP/gbw administered in multiple intraperitoneal (ip) injections can provide 40-50μg B per gram of tumor with acceptable toxicity. Toxicity experiments and a preliminary trial of BNCT in mice given such doses are also reported

Physical engineering and medical physics on boron neutron capture therapy

International Nuclear Information System (INIS)

Sakurai, Yoshinori

2011-01-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-11-01

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

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

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer

Energy Technology Data Exchange (ETDEWEB)

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

2016-05-01

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

The radiation biology of Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Coderre, J.A.

2003-01-01

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

Considerations for boron neutron capture therapy studies

International Nuclear Information System (INIS)

Faria Gaspar, P. de.

1994-01-01

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

BNCT Technology Development on HANARO Reactor

Energy Technology Data Exchange (ETDEWEB)

Chun, Ki Jung; Park, Kyung Bae; Whang, Seung Ryul; Kim, Myong Seop

2007-06-15

So as to establish the biological effects of BNCT in the HANARO Reactor, biological damages in cells and animals with treatment of boron/neutron were investigated. And 124I-BPA animal PET image, analysis technology of the boron contents in the mouse tissues by ICP-AES was established. A Standard clinical protocol, a toxicity evaluation report and an efficacy investigation report of BNCT has been developed. Based on these data, the primary permission of clinical application was acquired through IRB of our hospital. Three cases of pre-clinical experiment for boron distribution and two cases of medium-sized animal simulation experiment using cat with verifying for 2 months after BNCT was performed and so the clinical demonstration with a patient was prepared. Also neutron flux, fast neutron flux and gamma ray dose of BNCT facility were calculated and these data will be utilized good informations for clinical trials and further BNCT research. For the new synthesis of a boron compound, o-carboranyl ethylamine, o-carboranylenepiperidine, o-carboranyl-THIQ and o-carboranyl-s-triazine derivatives were synthesized. Among them, boron uptake in the cancer cell of the triazine derivative was about 25 times than that of BPA and so these three synthesized methods of new boron compounds were patented.

BNCT Technology Development on HANARO Reactor

International Nuclear Information System (INIS)

Chun, Ki Jung; Park, Kyung Bae; Whang, Seung Ryul; Kim, Myong Seop

2007-06-01

So as to establish the biological effects of BNCT in the HANARO Reactor, biological damages in cells and animals with treatment of boron/neutron were investigated. And 124I-BPA animal PET image, analysis technology of the boron contents in the mouse tissues by ICP-AES was established. A Standard clinical protocol, a toxicity evaluation report and an efficacy investigation report of BNCT has been developed. Based on these data, the primary permission of clinical application was acquired through IRB of our hospital. Three cases of pre-clinical experiment for boron distribution and two cases of medium-sized animal simulation experiment using cat with verifying for 2 months after BNCT was performed and so the clinical demonstration with a patient was prepared. Also neutron flux, fast neutron flux and gamma ray dose of BNCT facility were calculated and these data will be utilized good informations for clinical trials and further BNCT research. For the new synthesis of a boron compound, o-carboranyl ethylamine, o-carboranylenepiperidine, o-carboranyl-THIQ and o-carboranyl-s-triazine derivatives were synthesized. Among them, boron uptake in the cancer cell of the triazine derivative was about 25 times than that of BPA and so these three synthesized methods of new boron compounds were patented

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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.

Dose modification factors in boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Allen, B.J. (Australian Nuclear Science and Technology Organization (ANSTO), Menai (Australia))

1993-01-01

The effective treatment depth and therapeutic ratio in boron neutron capture therapy (BNCT) depend on a number of macroscopic dose factors such as boron concentrations in the tumor, normal tissue and blood. However, the role of various microscopic dose modification factors can be of critical importance in the evaluation of normal tissue tolerance levels. An understanding of these factors is valuable in designing BNCT experiments and the selection of appropriate boron compounds. These factors are defined in this paper and applied to the case of brain tumors with particular attention to capillary endothelial cells and oligodendrocytes. (orig.).

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Radiation shielding design of BNCT treatment room for D-T neutron source.

Science.gov (United States)

Pouryavi, Mehdi; Farhad Masoudi, S; Rahmani, Faezeh

2015-05-01

Recent studies have shown that D-T neutron generator can be used as a proper neutron source for Boron Neutron Capture Therapy (BNCT) of deep-seated brain tumors. In this paper, radiation shielding calculations have been conducted based on the computational method for designing a BNCT treatment room for a recent proposed D-T neutron source. By using the MCNP-4C code, the geometry of the treatment room has been designed and optimized in such a way that the equivalent dose rate out of the treatment room to be less than 0.5μSv/h for uncontrolled areas. The treatment room contains walls, monitoring window, maze and entrance door. According to the radiation protection viewpoint, dose rate results of out of the proposed room showed that using D-T neutron source for BNCT is safe. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

Kitaoka, Yoshinori

1993-09-01

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

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

International Nuclear Information System (INIS)

Coderre, J.A.; Greenberg, D.; Micca, P.L.; Joel, D.D.; Saraf, S.; Packer, S.

1990-01-01

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

Boron neutron capture therapy (BNCT) for high-grade gliomas of the brain: a cautionary note

International Nuclear Information System (INIS)

Laramore, George E.; Spence, Alexander M.

1996-01-01

Purpose/Objective: Boron neutron capture therapy (BNCT) is a method of treating high-grade gliomas of the brain that involves incorporating 10 B into the tumor using appropriate pharmacological agents and then irradiating the tumor with thermal or epithermal neutron beams. To date, over 120 patients have been treated in this manner by Japanese investigators using a thermal neutron beam from a nuclear reactor. Favorable reports on outcome have motivated considerable current research in BNCT. The purpose of this study is to provide an independent analysis of the Japanese data by identifying the subset of patients from the United States who received this treatment in Japan and comparing their outcomes relative to a matched cohort who received conventional therapy in various Radiation Therapy Oncology Group (RTOG) studies. Methods and Materials: The principal referral sources of patients to Japan for BNCT were identified and the names of patients sent for treatment obtained. The treating physicians in Japan were also contacted to see if additional patients from the United States had been treated. Either the patients or their next of kin were contacted, and permission was obtained to retrieve medical records including tumor pathology for central review. Prognostic variables according to an analysis of the RTOG brain tumor database by Curran et al. were determined from these records and used to construct a matched cohort of patients treated conventionally. Results: A total of 14 patients were identified who had traveled to Japan for BNCT treatment between July, 1987 and June, 1994. In the case of one patient (deceased), it was not possible to contact the next of kin. Material was obtained on the other 13 patients and review of the pathology indicated that 1 patient had a central nervous system lymphoma rather than a high-grade glioma. Survival data was analyzed for the other 12 patients on an actuarial basis, and this showed no difference compared to survival data for a

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

International Nuclear Information System (INIS)

Awadalla, Galaleldin Mohamed Suliman

2015-11-01

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

Boron-containing thioureas for neutron capture therapy. Borhaltige Thioharnstoffe fuer die Neutroneneinfangtherapie

Energy Technology Data Exchange (ETDEWEB)

Ketz, H.

1993-10-21

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

Possible application of boron neutron capture therapy to canine osteosarcoma

International Nuclear Information System (INIS)

Takeuchi, Akira

1985-01-01

Possibility for successful treatment of canine osteosarcoma by boron neutron capture therapy (BNCT) was demonstrated based upon an uptake study of the boron compound and an experimental treatment by BNCT. In the up take study following intravenous administration of Na 2 B 12 H 11 SH, satisfactorily higher boron concentration with some variation between tumors is likely to be obtained 12 hours after the administration, together with significantly lower boron levels in blood and bone. Based upon these results, osteosarcoma of a mongrel dog was successfully treated by BNCT. The tumor received approximately 3800 rads with single neutron irradiation (approximately 1.4 x 10 13 n./cm 2 ) about 12 hours after intravenous infusion of Na 2 B 12 H 11 SH of 96 % enriched 10 B in the ratio of 50 mg 10 B/kg. Clinical and radiographical improvements were remarkable and no neoplastic cell was found in any part of the original neoplastic lesion and its surrounding tissue at the time of autopsy after 30 days. (author)

Role of gel dosimeters in boron neutron capture therapy

International Nuclear Information System (INIS)

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

2015-01-01

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

Characterisation of an accelerator-based neutron source for BNCT versus beam energy

Science.gov (United States)

Agosteo, S.; Curzio, G.; d'Errico, F.; Nath, R.; Tinti, R.

2002-01-01

Neutron capture in 10B produces energetic alpha particles that have a high linear energy transfer in tissue. This results in higher cell killing and a higher relative biological effectiveness compared to photons. Using suitably designed boron compounds which preferentially localize in cancerous cells instead of healthy tissues, boron neutron capture therapy (BNCT) has the potential of providing a higher tumor cure rate within minimal toxicity to normal tissues. This clinical approach requires a thermal neutron source, generally a nuclear reactor, with a fluence rate sufficient to deliver tumorcidal doses within a reasonable treatment time (minutes). Thermal neutrons do not penetrate deeply in tissue, therefore BNCT is limited to lesions which are either superficial or otherwise accessible. In this work, we investigate the feasibility of an accelerator-based thermal neutron source for the BNCT of skin melanomas. The source was designed via MCNP Monte Carlo simulations of the thermalization of a fast neutron beam, generated by 7 MeV deuterons impinging on a thick target of beryllium. The neutron field was characterized at several deuteron energies (3.0-6.5 MeV) in an experimental structure installed at the Van De Graaff accelerator of the Laboratori Nazionali di Legnaro, in Italy. Thermal and epithermal neutron fluences were measured with activation techniques and fast neutron spectra were determined with superheated drop detectors (SDD). These neutron spectrometry and dosimetry studies indicated that the fast neutron dose is unacceptably high in the current design. Modifications to the current design to overcome this problem are presented.

Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: Trial using a lung metastasis model of CCS.

Science.gov (United States)

Andoh, Tooru; Fujimoto, Takuya; Suzuki, Minoru; Sudo, Tamotsu; Sakurai, Yoshinori; Tanaka, Hiroki; Fujita, Ikuo; Fukase, Naomasa; Moritake, Hiroshi; Sugimoto, Tohru; Sakuma, Toshiko; Sasai, Hiroshi; Kawamoto, Teruya; Kirihata, Mitsunori; Fukumori, Yoshinobu; Akisue, Toshihiro; Ono, Koji; Ichikawa, Hideki

2015-12-01

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In the present study, we established a lung metastasis animal model of CCS and investigated the therapeutic effect of boron neutron capture therapy (BNCT) using p-borono-L-phenylalanine (L-BPA). Biodistribution data revealed tumor-selective accumulation of (10)B. Unlike conventional gamma-ray irradiation, BNCT significantly suppressed tumor growth without damaging normal tissues, suggesting that it may be a potential new therapeutic option to treat CCS lung metastases. Copyright © 2015 Elsevier Ltd. All rights reserved.

MCNP study for epithermal neutron irradiation of an isolated liver at the Finnish BNCT facility.

Science.gov (United States)

Kotiluoto, P; Auterinen, I

2004-11-01

A successful boron neutron capture treatment (BNCT) of a patient with multiple liver metastases has been first given in Italy, by placing the removed organ into the thermal neutron column of the Triga research reactor of the University of Pavia. In Finland, FiR 1 Triga reactor with an epithermal neutron beam well suited for BNCT has been extensively used to irradiate patients with brain tumors such as glioblastoma and recently also head and neck tumors. In this work we have studied by MCNP Monte Carlo simulations, whether it would be beneficial to treat an isolated liver with epithermal neutrons instead of thermal ones. The results show, that the epithermal field penetrates deeper into the liver and creates a build-up distribution of the boron dose. Our results strongly encourage further studying of irradiation arrangement of an isolated liver with epithermal neutron fields.

Synthesis and in-vivo detection of boronated compounds for use in BNCT

International Nuclear Information System (INIS)

Kabalka, G.W.

1990-04-01

The primary objective of the DOE Program at the University of Tennessee Biomedical Imaging Center is the development of new technology to detect boron compounds in-vivo. The research focuses on the development of multinuclear magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques for verifying and measuring BNCT agents in-vivo. A small but significant portion of the effort is directed toward the design of boron-containing neutron-capture-therapy agents. The UT -- DOE program is unique in that it has access to two state-of-the-art multinuclear magnetic resonance imaging units housed in the Biomedical Imaging Center at the University of Tennessee Medical Center at Knoxville. Included in this report are two sections describing research accomplishments in multinuclear magnetic resonance imaging and synthesis of potential BNCT agents

A critical assessment of boron target compounds for boron neutron capture therapy.

Science.gov (United States)

Hawthorne, M Frederick; Lee, Mark W

2003-01-01

Boron neutron capture therapy (BNCT) has undergone dramatic developments since its inception by Locher in 1936 and the development of nuclear energy during World War II. The ensuing Cold War spawned the entirely new field of polyhedral borane chemistry, rapid advances in nuclear reactor technology and a corresponding increase in the number to reactors potentially available for BNCT. This effort has been largely oriented toward the eradication of glioblastoma multiforme (GBM) and melanoma with reduced interest in other types of malignancies. The design and synthesis of boron-10 target compounds needed for BNCT was not channeled to those types of compounds specifically required for GBM or melanoma. Consequently, a number of potentially useful boron agents are known which have not been biologically evaluated beyond a cursory examination and only three boron-10 enriched target species are approved for human use following their Investigational New Drug classification by the US Food and Drug Administration; BSH, BPA and GB-10. All ongoing clinical trials with GBM and melanoma are necessarily conducted with one of these three species and most often with BPA. The further development of BNCT is presently stalled by the absence of strong support for advanced compound evaluation and compound discovery driven by recent advances in biology and chemistry. A rigorous demonstration of BNCT efficacy surpassing that of currently available protocols has yet to be achieved. This article discusses the past history of compound development, contemporary problems such as compound classification and those problems which impede future advances. The latter include means for biological evaluation of new (and existing) boron target candidates at all stages of their development and the large-scale synthesis of boron target species for clinical trials and beyond. The future of BNCT is bright if latitude is given to the choice of clinical disease to be treated and if a recognized study

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Spectrum shaping of accelerator-based neutron beams for BNCT

CERN Document Server

Montagnini, B; Esposito, J; Giusti, V; Mattioda, F; Varone, R

2002-01-01

We describe Monte Carlo simulations of three facilities for the production of epithermal neutrons for Boron Neutron Capture Therapy (BNCT) and examine general aspects and problems of designing the spectrum-shaping assemblies to be used with these neutron sources. The first facility is based on an accelerator-driven low-power subcritical reactor, operating as a neutron amplifier. The other two facilities have no amplifier and rely entirely on their primary sources, a D-T fusion reaction device and a conventional 2.5 MeV proton accelerator with a Li target, respectively.

Recombination methods for boron neutron capture therapy dosimetry

International Nuclear Information System (INIS)

Golnik, N.; Tulik, P.; Zielczynski, M.

2003-01-01

The radiation effects of boron neutron capture therapy (BNCT) are associated with four-dose-compartment radiation field - boron dose (from 10 B(n,α) 7 Li) reaction), proton dose from 14 N(n,p) 14 C reaction, neutron dose (mainly fast and epithermal neutrons) and gamma-ray dose (external and from capture reaction 1 H(n,γ) 2 D). 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, 10 BF 3 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, 10 B) reaction in simulated tissue with different content of 10 B. (author)

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

OpenAIRE

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

2010-01-01

Abstract Background Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation. Methods The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical Un...

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-11-15

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Feasibility of sealed D-T neutron generator as neutron source for liver BNCT and its beam shaping assembly.

Science.gov (United States)

Liu, Zheng; Li, Gang; Liu, Linmao

2014-04-01

This paper involves the feasibility of boron neutron capture therapy (BNCT) for liver tumor with four sealed neutron generators as neutron source. Two generators are placed on each side of the liver. The high energy of these emitted neutrons should be reduced by designing a beam shaping assembly (BSA) to make them useable for BNCT. However, the neutron flux decreases as neutrons pass through different materials of BSA. Therefore, it is essential to find ways to increase the neutron flux. In this paper, the feasibility of using low enrichment uranium as a neutron multiplier is investigated to increase the number of neutrons emitted from D-T neutron generators. The neutron spectrum related to our system has a proper epithermal flux, and the fast and thermal neutron fluxes comply with the IAEA recommended values. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2008-04-01

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

Response of the oral mucosa to porphyrin mediated boron neutron capture therapy

International Nuclear Information System (INIS)

Morris, G.M.

2003-01-01

Pre-clinical studies are now in progress to develop boron neutron capture therapy (BNCT) modalities for the treatment of head and neck carcinomas. BNCT is a bimodal therapy which involves the administration of a boron-10 enriched compound, that accumulates preferentially in tumours, prior to irradiation with low energy neutrons. These neutrons are captured by boron-10 atoms to produce a highly localised radiation exposure. More recently, it has been demonstrated that various boronated porphyrins can target a variety of tumours. Of the porphyrins evaluated to date, copper tetracarboranylphenyl porphyrin (CuTCPH) is a strong candidate for potential clinical evaluation. It has extremely high specificity for a variety of tumour models. Therapeutic efficacy of CuTCPH mediated BNCT has been demonstrated in pre-clinical studies using the murine EMT-6 carcinoma model. In the present investigation the response of the oral mucosa to CuTCPH mediated boron neutron capture (BNC) irradiation was assessed using a standard rat model (ventral tongue). Single exposure irradiation was carried out on the thermal neutron beam at the Brookhaven Medical Research Reactor, at 3 days after the final injection of the boronated porphyrin. The impact of CuTCPH mediated BNC irradiation on oral mucosa at therapeutically effective exposure times, assessed using the ventral tongue model, was minimal. This was primarily due to the fact that blood boron levels (from CuTCPH) were very low at the time of irradiation. Analysis of the dose-effect data for CuTCPH gave a compound biological effectiveness (CBE) factor of 2.5. It can be concluded that, although, the CBE factor (calculated using blood boron concentrations) was relatively high, CuTCPH mediated BNC irradiation should not cause significant damage at clinically relevant radiation doses. This is because blood boron levels would be very low at the time of irradiation

Epithermal neutron beam for BNCT research at the Washington State University TRIGA research reactor

International Nuclear Information System (INIS)

Nigg, D.W.; Venhuizen, J.R.; Wheeler, F.J.; Wemple, C.A.; Tripard, G.E.; Gavin, P.R.

2000-01-01

A new epithermal-neutron beam facility for BNCT (Boron Neutron Capture Therapy) research and boronated agent screening in animal models is in the final stages of construction at Washington State University (WSU). A key distinguishing feature of the design is the incorporation of a new, high-efficiency, neutron moderating and filtering material, Fluental, developed by the Technical Research Centre of Finland. An additional key feature is the provision for adjustable filter-moderator thickness to systematically explore the radiobiological consequences of increasing the fast-neutron contamination above the nominal value associated with the baseline system. (author)

Perspectives of boron-neutron capture therapy of malignant brain tumors

Science.gov (United States)

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

2017-09-01

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

Carborane derivative development for boron neutron capture therapy. Final report

International Nuclear Information System (INIS)

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

1999-01-01

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

OPTIMIZATION OF A NEUTRON BEAM SHAPING ASSEMBLY DESIGN FOR BNCT AND ITS DOSIMETRY SIMULATION BASED ON MCNPX

Directory of Open Access Journals (Sweden)

I Made Ardana

2017-10-01

OPTIMASI DESAIN KOLIMATOR NEUTRON UNTUK SISTEM BNCT DAN UJI DOSIMETRINYA MENGGUNAKAN PROGRAM MCNPX. Telah dilakukan penelitian tentang sistem BNCT yang meliputi dua tahapan simulasi dengan menggunakan program MCNPX yaitu uji simulasi untuk optimasi desain kolimator neutron untuk sistem BNCT berbasis Siklotron 30 MeV dan uji simulasi untuk menghitung fluks neutron dan dosimetri radiasi pada kanker sarkoma jaringan lunak pada leher dan kepala. Tujuan simulasi untuk mendapatkan desain kolimator yang paling optimal dalam memoderasi fluks neutron cepat yang dihasilkan dari sistem target berilium sehingga dapat dihasilkan fluks neutron yang sesuai untuk sistem BNCT. Uji optimasi dilakukan dengan cara memvariasikan bahan dan ketebalan masing-masing komponen dalam kolimator seperi reflektor, moderator, filter neutron cepat, filter neutron thermal, filter radiasi gamma dan lubang keluaran. Desain kolimator yang diperoleh dari hasil optimasi tersusun atas moderator berbahan Al dengan ketebalan 39 cm, filter neutron cepat berbahan LiF2 setebal 8,2 cm, dan filter neutron thermal berbahan B4C setebal 0,5 cm. Untuk reflektor, filter radiasi gamma dan lubang keluaran masing-masing menggunakan bahan PbF2, Pb dan Bi. Fluks neutron epithermal yang dihasilkan dari kolimator yang didesain adalah sebesar 2,83 x 109 n/s cm-2 dan telah memenuhi seluruh parameter fluks neutron yang sesuai untuk sistem BNCT. Selanjutnya uji simulasi dosimetri pada kanker sarkoma jaringan lunak pada leher dan kepala dilakukan dengan cara memvariasikan konsentrasi senyawa boron pada model phantom leher manusia (ORNL. Selanjutnya model phantom tersebut diiradiasi dengan fluks neutron yang berasal dari kolimator yang telah didesain sebelumnya. Hasilnya, fluks neutron thermal mencapai nilai tertinggi pada kedalaman 4,8 cm di dalam model phantom leher ORNL dengan laju dosis tertinggi terletak pada area jaringan kanker. Untuk masing-masing variasi konsentrasi senyawa boron pada model phantom leher ORNL supaya

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.

Selective enhancement of boron accumulation with boron-entrapped water-in-oil-water emulsion in VX-2 rabbit hepatic cancer model for BNCT

International Nuclear Information System (INIS)

Yanagie, Hironobu; Higashi, Shushi; Ikushima, Ichiro

2006-01-01

Tumor cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10 B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate 10 B atoms in the tumor cells without affecting adjacent healthy cells. Water-in-oil-water (WOW) emulsion was used as the carrier of anti-cancer agents on arterial injections in clinical cancer treatment. In this study, we prepared 10 BSH entrapped WOW emulsion for selective arterial infusion for the treatment of hepatocellular carcinoma. WOW emulsion was administrated by arterial injections via proper hepatic artery. The anti-tumor activity of the emulsion was compared with 10 BSH-Lipiodol mix emulsion or 10 BSH solutions on VX-2 rabbit hepatic tumor models. The 10 B concentrations in VX-2 tumor on delivery with WOW emulsion was superior to those by conventional lipiodol mix emulsion. Electro-microscopic figures of WOW emulsion delineated the accumulation of fat droplets of WOW emulsion in the tumor site, but there was no accumulation of fat droplets in lipiodol emulsion. These results indicate that 10 B entrapped WOW emulsion is most useful carrier for arterial delivery of boron agents on BNCT to cancer. (author)

Use of the Power Burst Facility for boron neutron capture therapy

International Nuclear Information System (INIS)

Crocker, J.G.; Griebenow, M.L.; Leatham, J.

1990-01-01

A program is under development at the Idaho National Engineering Laboratory (INEL) that involves using the Power Burst Facility (PBF) for research into boron neutron capture therapy (BNCT). BNCT utilizes the ionizing energy from boron-neutron capture to stop reproduction of or destroy cells in cancerous tissue in a two-step process. The first step is to selectively concentrate a boron isotope within the tumor cell, that when activated by neutron capture emits highly ionizing, short range particles. The second step involves activation of the isotope only in the vicinity of the tumor with a narrow neutron beam. The ( 10 B[n, 4 He] 7 Li) reaction with thermal neutrons produces fission products with track lengths approximately equal to a cell diameter. The INEL program includes the modification of the PBF by the addition of a filter and treatment area. The filter will down-scatter high energy neutrons into the epithermal range and remove thermal neutrons and excessively damaging gamma components. The intense source of epithermal neutrons from PBF is considered necessary to achieve optimum therapy for deep-seated tumors with minimum damage to surface tissue. THe neutron filter conceptualized for PBF utilizes aluminum and heavy water to down-scatter neutrons into the proper energy range. Bismuth will be used for gamma shielding and cadmium will remove the thermal neutron contaminant from the beam. The INEL program leads to human clinical trials at PBF which are intended to prove that brain tumors can be successfully treated through noninvasive techniques. Further research into BNCT at PBF for other cancer types is also anticipated

Folate Functionalized Boron Nitride Nanotubes and their Selective Uptake by Glioblastoma Multiforme Cells: Implications for their Use as Boron Carriers in Clinical Boron Neutron Capture Therapy.

Science.gov (United States)

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

2008-11-25

Boron neutron capture therapy (BNCT) is increasingly being used in the treatment of several aggressive cancers, including cerebral glioblastoma multiforme. The main requirement for this therapy is selective targeting of tumor cells by sufficient quantities of (10)B atoms required for their capture/irradiation with low-energy thermal neutrons. The low content of boron targeting species in glioblastoma multiforme accounts for the difficulty in selective targeting of this very malignant cerebral tumor by this radiation modality. In the present study, we have used for the first time boron nitride nanotubes as carriers of boron atoms to overcome this problem and enhance the selective targeting and ablative efficacy of BNCT for these tumors. Following their dispersion in aqueous solution by noncovalent coating with biocompatible poly-l-lysine solutions, boron nitride nanotubes were functionalized with a fluorescent probe (quantum dots) to enable their tracking and with folic acid as selective tumor targeting ligand. Initial in vitro studies have confirmed substantive and selective uptake of these nanovectors by glioblastoma multiforme cells, an observation which confirms their potential clinical application for BNCT therapy for these malignant cerebral tumors.

Folate Functionalized Boron Nitride Nanotubes and their Selective Uptake by Glioblastoma Multiforme Cells: Implications for their Use as Boron Carriers in Clinical Boron Neutron Capture Therapy

Directory of Open Access Journals (Sweden)

Ciofani Gianni

2008-01-01

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

Boron neutron capture therapy induces cell cycle arrest and DNA fragmentation in murine melanoma cells

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. [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.br [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)

2011-12-15

The melanoma is a highly lethal skin tumor, with a high incidence. Boron Neutron Capture Therapy (BNCT) is a radiotherapy which combines Boron with thermal neutrons, constituting a binary system. B16F10 melanoma and L929 fibroblasts were treated with Boronophenylalanine and irradiated with thermal neutron flux. The electric potential of mitochondrial membrane, cyclin D1 and caspase-3 markers were analyzed. BNCT induced a cell death increase and cyclin D1 amount decreased only in B16F10 melanoma. Besides, there was not caspase-3 phosphorylation.

Boron concentration measurements by alpha spectrometry and quantitative neutron autoradiography in cells and tissues treated with different boronated formulations and administration protocols

International Nuclear Information System (INIS)

Bortolussi, Silva; Ciani, Laura; Postuma, Ian; Protti, Nicoletta; Luca Reversi,; Bruschi, Piero; Ferrari, Cinzia; Cansolino, Laura; Panza, Luigi; Ristori, Sandra; Altieri, Saverio

2014-01-01

The possibility to measure boron concentration with high precision in tissues that will be irradiated represents a fundamental step for a safe and effective BNCT treatment. In Pavia, two techniques have been used for this purpose, a quantitative method based on charged particles spectrometry and a boron biodistribution imaging based on neutron autoradiography. A quantitative method to determine boron concentration by neutron autoradiography has been recently set-up and calibrated for the measurement of biological samples, both solid and liquid, in the frame of the feasibility study of BNCT. This technique was calibrated and the obtained results were cross checked with those of α spectrometry, in order to validate them. The comparisons were performed using tissues taken form animals treated with different boron administration protocols. Subsequently the quantitative neutron autoradiography was employed to measure osteosarcoma cell samples treated with BPA and with new boronated formulations. - Highlights: • A method for 10B measurements in samples based on neutron autoradiography was developed. • The results were compared with those of alpha spectrometry applied on tissue and cell samples. • Boronated liposomes were developed and administered to osteosarcoma cell cultures. • Neutron autoradiography was employed to measure boron concentration due to liposomes. • Liposomes were proved to be more effective in concentrating boron in cells than BPA

Capability of NIPAM polymer gel in recording dose from the interaction of 10B and thermal neutron in BNCT

International Nuclear Information System (INIS)

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

2015-01-01

The capability of N-isopropylacrylamide (NIPAM) polymer gel to record the dose resulting from boron neutron capture reaction in BNCT was determined. In this regard, three compositions of the gel with different concentrations of 10 B were prepared and exposed to gamma radiation and thermal neutrons. Unlike irradiation with gamma rays, the boron-loaded gels irradiated by neutron exhibited sensitivity enhancement compared with the gels without 10 B. It was also found that the neutron sensitivity of the gel increased by the increase of concentration of 10 B. It can be concluded that NIPAM gel might be suitable for the measurement of the absorbed dose enhancement due to 10 B and thermal neutron reaction in BNCT. - Highlights: • Three compositions of NIPAM gel with different concentration of 10 B have been exposed by gamma and thermal neutron. • The vials containing NIPAM gel have been irradiated by an automatic system capable of providing for dose uniformity. • Suitability of NIPAM polymer gel in measuring radiation doses in BNCT has been investigated.

A technique to prepare boronated B72.3 monoclonal antibody for boron neutron capture therapy

International Nuclear Information System (INIS)

Ranadive, G.N.; Rosenzweig, H.S.; Epperly, M.W.

1993-01-01

B72.3 monoclonal antibody has been successfully boronated using mercaptoundecahydro-closo-dodecaborate (boron cage compound). The reagent was incorporated by first reacting the lysine residues of the antibody with m-maleimidobenzoyl succinimide ester (MBS), followed by Michael addition to the maleimido group by the mercapto boron cage compound to form a physiologically stable thioether linkage. Boron content of the antibody was determined by atomic absorption spectroscopy. For biodistribution studies, boronated antibody was radioiodinated with iodogen. 125 I-labeled and boronated B72.3 monoclonal antibody demonstrated clear tumor localization when administered via tail vein injections to athymic nude mice bearing LS174-T tumor xenografts. Boronated antibody was calculated to deliver 10 6 boron atoms per tumor cell. Although this falls short of the specific boron content originally proposed as necessary for boron neutron capture therapy (BNCT), recent calculations suggest that far fewer atoms of 10 B per tumor cell would be necessary to effect successful BNCT when the boron is targeted to the tumor cell membrane. (author)

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

International Nuclear Information System (INIS)

Vicente, M.G.H.; Wickramasinghe, A.; Shetty, S.J.; Smith, K.M.

2000-01-01

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)

Anesthetic management of Boron Neutron Capture Therapy for glioblastoma

International Nuclear Information System (INIS)

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

2000-01-01

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

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

International Nuclear Information System (INIS)

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

1997-01-01

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

INEL BNCT Research Program annual report 1994

International Nuclear Information System (INIS)

Venhuizen, J.R.

1995-11-01

This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1994. Contributions from the principal investigators about their individual projects are included, specifically, chemistry (pituitary tumor studies, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, ICP-AES analysis of biological samples), physics (treatment planning software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (small and large animal models tissue studies and efficacy studies). Information on the potential toxicity of BSH and BPA is presented and results of 21 spontaneous tumor bearing dogs that have been treated with BNCT at Brookhaven National Laboratory (BNL) are discussed. Several boron carrying drugs exhibiting good tumor uptake are described. Significant progress in the potential of treating pituitary tumors is presented. Highlights from the First International Workshop on Accelerator-Based Neutron Sources for BNCT are included

A D-D/D-T fusion reaction based neutron generator system for liver tumor BNCT

International Nuclear Information System (INIS)

Koivunoro, H.; Lou, T.P.; Leung, K. N.; Reijonen, J.

2003-01-01

Boron-neutron capture therapy (BNCT) is an experimental radiation treatment modality used for highly malignant tumor treatments. Prior to irradiation with low energetic neutrons, a 10B compound is located selectively in the tumor cells. The effect of the treatment is based on the high LET radiation released in the 10 B(n,α) 7 Li reaction with thermal neutrons. BNCT has been used experimentally for brain tumor and melanoma treatments. Lately applications of other severe tumor type treatments have been introduced. Results have shown that liver tumors can also be treated by BNCT. At Lawrence Berkeley National Laboratory, various compact neutron generators based on D-D or D-T fusion reactions are being developed. The earlier theoretical studies of the D-D or D-T fusion reaction based neutron generators have shown that the optimal moderator and reflector configuration for brain tumor BNCT can be created. In this work, the applicability of 2.5 MeV neutrons for liver tumor BNCT application was studied. The optimal neutron energy for external liver treatments is not known. Neutron beams of different energies (1eV < E < 100 keV) were simulated and the dose distribution in the liver was calculated with the MCNP simulation code. In order to obtain the optimal neutron energy spectrum with the D-D neutrons, various moderator designs were performed using MCNP simulations. In this article the neutron spectrum and the optimized beam shaping assembly for liver tumor treatments is presented

Development of cancer therapy facility of HANARO and medical research in BNCT; development of the technique for boron concentration analysis

Energy Technology Data Exchange (ETDEWEB)

Choi, Hee Dong; Byun, Soo Hyun; Sun, Gwang Min; Kim, Suk Kwon; Kim, In Jung; Park, Chang Su [Seoul National University, Seoul (Korea)

2002-03-01

Objective and Necessity of the Project- Development of a boron concentration analysis facility used for BNCT. - Development of the technique for boron concentration analysis. Contents and Scopes of the Project - Construction of the boron concentration analysis facility based on PGAA. Estimation of the neutron beam characteristics. -Establishment of the technique for the boron concentration analysis. - Estimation of the reliability for the boron analysis. Results of the Project -Installation of the boron concentration analysis facility at Hanaro. - Neutron beam characteristics are the sample position (neutron flux : 7.9 x 10{sup 7} n/cm{sup 2}s, Cd-ratio : 266) Technique for the boron concentration analysis. - Boron detection sensitivity and limit (detection sensitivity : 2, 131 cps/mg-B, detection limit : 67 ng for 10,000 sec). 63 refs., 37 figs., 13 tabs. (Author)

Investigation of boron conjugated thiouracil derivates for neutron capture therapy of melanoma

International Nuclear Information System (INIS)

Corderoy-Buck, S.; Allen, B.J.; Wilson, J.G.; Tjarks, W.; Gabel, D.; Barkla, D.; Patwardhan, A.; Chandler, A.; Moore, D.E.

1990-01-01

Boron conjugated thiouracil derivatives were investigated as possible agents for boron neutron capture therapy (BNCT) of melanoma. Nude mice bearing human or murine melanoma xenografts were used for biodistribution studies following i.p. or i.t. (intratumoural) injection of these drugs. Boron content was analysed by inductively coupled plasma atomic emission spectrometry. Wide variation between tumour lines was observed with respect to accumulation of these drugs, but they appear to offer potential as melanoma affined boron carriers if solubility problems are overcome by liposome entrapment. Pre-treatment to stimulate melanogenesis may also prove a useful adjunct in achieving the therapeutic concentrations of boron necessary for successful BNCT. 25 refs., 4 tabs., 3 figs

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

International Nuclear Information System (INIS)

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

2015-01-01

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

SERA -- An advanced treatment planning system for neutron therapy and BNCT

International Nuclear Information System (INIS)

Nigg, D.W.; Wemple, C.A.; Wessol, D.E.; Wheeler, F.J.; Albright, C.; Cohen, M.; Frandsen, M.; Harkin, G.; Rossmeier, M.

1999-01-01

Detailed treatment planning calculations on a patient-specific basis are required for boron neutron capture therapy (BNCT). Two integrated treatment planning systems developed specifically for BNCT have been in clinical use in the United States over the past few years. The MacNCTPLAN BNCT treatment planning system is used in the clinical BNCT trials that are underway at the Massachusetts Institute of Technology. A second system, BNCT rtpe (BNCT radiation therapy planning environment), developed independently by the Idaho national Engineering and Environmental Laboratory (INEEL) in collaboration with Montana State University (MSU), is used for treatment planning in the current series of BNCT clinical trials for glioblastoma at Brookhaven National Laboratory (BNL). This latter system is also licensed for use at several other BNCT research facilities worldwide. Although the currently available BNCT planning systems have served their purpose well, they suffer from somewhat long computation times (2 to 3 CPU-hours or more per field) relative to standard photon therapy planning software. This is largely due to the need for explicit three-dimensional solutions to the relevant transport equations. The simplifying approximations that work well for photon transport computations are not generally applicable to neutron transport computations. Greater computational speeds for BNCT treatment planning must therefore generally be achieved through the application of improved numerical techniques rather than by simplification of the governing equations. Recent efforts at INEEL and MSU have been directed toward this goal. This has resulted in a new paradigm for this type of calculation and the subsequent creation of the new simulation environment for radiotherapy applications (SERA) treatment planning system for BNCT. SERA is currently in initial clinical testing in connection with the trials at BNL, and it is expected to replace the present BNCT rtpe system upon general release

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

Radiation Transport Simulation for Boron Neutron Capture Therapy (BNCT)

Energy Technology Data Exchange (ETDEWEB)

Ziegner, M.; Blaickner, M. [AIT Austrian Institute of Technology GmbH, Health and Environment Department, Molecular Medicine, Muthgasse 11, 1190 Wien (Austria); Ziegner, M.; Khan, R.; Boeck, H. [Vienna University of Technology, Institute of Atomic and Subatomic Physics, Stadionallee 2, 1020 Wien (Austria); Bortolussi, S.; Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, National Institute of Nuclear Physics (INFN) Pavia Section, Pavia (Italy); Schmitz, T.; Hampel, G. [Nuclear Chemistry, University of Mainz, Fritz Strassmann Weg 2, 55099 Mainz (Germany)

2011-07-01

This work is part of a larger project initiated by the University of Mainz and aiming to use the university's TRIGA reactor to develop a treatment for liver metastases based on Boron Neutron Capture Therapy (BNCT). Diffuse distribution of cancerous cells within the organ makes complete resection difficult and the vicinity to radiosensitive organs impedes external irradiation. Therefore the method of 'autotransplantation', first established at the University of Pavia, is used. The liver is taken out of the body, irradiated in the thermal column of the reactor, therewith purged of metastases and then reimplanted. A highly precise dosimetry system is to be developed by means of measurements at the University of Mainz and computational calculations at the AIT. The stochastic MCNP-5 Monte Carlo-Code, developed by Los Alamos Laboratories, is applied. To verify the calculations of the flux and the absorbed dose in matter a number of measurements are performed irradiating different phantoms and liver sections in a 20cm x 20cm beam tube, which was created by removing graphite blocks from the thermal column of the reactor. The detector material consists of L- {alpha} -alanine pellets which are thought to be the most suitable because of their good tissue equivalence, small size and their wide response range. Another experiment focuses on the determination of the relative biological effectiveness (RBE-factor) of the neutron and photon dose for liver cells. Therefore cell culture plates with the cell medium enriched with {sup 157}Gd and {sup 10}B at different concentrations are irradiated. With regard to the alanine pellets MCNP-5 calculations give stable results. Nevertheless the absorbed dose is underestimated compared to the measurements, a phenomenon already observed in previous works. The cell culture calculations showed the enormous impact of the added isotopes with high thermal neutron cross sections, especially {sup 157}Gd, on the absorbed dose

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.

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

International Nuclear Information System (INIS)

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

1996-01-01

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

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

International Nuclear Information System (INIS)

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

1999-01-01

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

Design of experiment existing parameter physics for supporting of Boron Neutron Capture Therapy (BNCT) method a t the piercing radial beam port of Kartini research reactor

International Nuclear Information System (INIS)

Indry Septiana Novitasari; Yosaphat Sumardi; Widarto

2014-01-01

The experiment existing parameters physics for supporting of in vivo and in vitro test facility of Boron Neutron Capture Therapy (BNCT) preliminary study at the piercing radial beam port has been done. The existing experiments is needed for determining that the parameter physics is fulfill the BNCT method requirement. To realize the existing experiment have been done by design analysis, methodology, calculation method and some procedure related with radiation safety analysis and environment. Preparation for existing experiment physics such as foil detector of Gold (Au) should be irradiated for 30 minute, irradiation instrument and procedure related with the experiment for radiation safety. (author)

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

International Nuclear Information System (INIS)

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

1993-01-01

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

INEL BNCT Research Program annual report 1994

Energy Technology Data Exchange (ETDEWEB)

Venhuizen, J.R. [ed.

1995-11-01

This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1994. Contributions from the principal investigators about their individual projects are included, specifically, chemistry (pituitary tumor studies, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, ICP-AES analysis of biological samples), physics (treatment planning software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (small and large animal models tissue studies and efficacy studies). Information on the potential toxicity of BSH and BPA is presented and results of 21 spontaneous tumor bearing dogs that have been treated with BNCT at Brookhaven National Laboratory (BNL) are discussed. Several boron carrying drugs exhibiting good tumor uptake are described. Significant progress in the potential of treating pituitary tumors is presented. Highlights from the First International Workshop on Accelerator-Based Neutron Sources for BNCT are included. Selected papers have been indexed separately for inclusion in the Energy Science and Technology Database.

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

Directory of Open Access Journals (Sweden)

Charles A Maitz

2017-08-01

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

Analytical dosimetry for spontaneous tumor dogs receiving boron neutron capture therapy

International Nuclear Information System (INIS)

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

1992-01-01

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

Cyclotron-based neutron source for BNCT

Energy Technology Data Exchange (ETDEWEB)

Mitsumoto, T.; Yajima, S.; Tsutsui, H.; Ogasawara, T.; Fujita, K. [Sumitomo Heavy Industries, Ltd (Japan); Tanaka, H.; Sakurai, Y.; Maruhashi, A. [Kyoto University Research Reactor Institute (Japan)

2013-04-19

Kyoto University Research Reactor Institute (KURRI) and Sumitomo Heavy Industries, Ltd. (SHI) have developed a cyclotron-based neutron source for Boron Neutron Capture Therapy (BNCT). It was installed at KURRI in Osaka prefecture. The neutron source consists of a proton cyclotron named HM-30, a beam transport system and an irradiation and treatment system. In the cyclotron, H- ions are accelerated and extracted as 30 MeV proton beams of 1 mA. The proton beams is transported to the neutron production target made by a beryllium plate. Emitted neutrons are moderated by lead, iron, aluminum and calcium fluoride. The aperture diameter of neutron collimator is in the range from 100 mm to 250 mm. The peak neutron flux in the water phantom is 1.8 Multiplication-Sign 109 neutrons/cm{sup 2}/sec at 20 mm from the surface at 1 mA proton beam. The neutron source have been stably operated for 3 years with 30 kW proton beam. Various pre-clinical tests including animal tests have been done by using the cyclotron-based neutron source with {sup 10}B-p-Borono-phenylalanine. Clinical trials of malignant brain tumors will be started in this year.

Primary study for boron neutron capture therapy uses the RSG-GAS beam tube facility

International Nuclear Information System (INIS)

Suroso

2000-01-01

The minimum epithermal neutron flux as one of the prerequisite of Boron Neutron Capture Therapy (BNCT) is 1.0 x 10 9 n/(cm 2 s) RSG-GAS have 6 beam tube facilities for neutron source, which is one of the beam tube S-2 has a possibility to utilization for BNCT facility. The totally flux neutron measurement in the front of S-2 beam tube is 1.8 x 10 7 n/(cm 2 s). The neutron flux measurement was less than for BNCT minimum prerequisite. Concerning to the flux neutron production in the reactor, which is reach to 2.5 x 10 14 n/(cm 2 s), there for the S-2 beam tube could be used beside collimator modification

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Neutron autoradiography imaging of selective boron uptake in human metastatic tumours

Energy Technology Data Exchange (ETDEWEB)

Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, Via Bassi 6, Pavia (Italy)], E-mail: saverio.altieri@pv.infn.it; Bortolussi, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, Via Bassi 6, Pavia (Italy); Bruschi, P.; Chiari, P.; Fossati, F.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Prati, U.; Roveda, L. [Unit of cancer surgery, Cancer Center of Excellence, Foundation T. Campanella, Catanzaro (Italy); Zonta, A.; Zonta, C.; Ferrari, C.; Clerici, A. [Department of Surgery, University of Pavia, Piazza Botta, Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, Piazza Botta, Pavia (Italy); Pinelli, T. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, Via Bassi 6, Pavia (Italy)

2008-12-15

The ability to selectively hit the tumour cells is an essential characteristic of an anti-tumour therapy. In boron neutron capture therapy (BNCT) this characteristic is based on the selective uptake of {sup 10}B in the tumour cells with respect to normal tissues. An important step in the BNCT planning is the measurement of the boron concentration in the tissue samples, both tumour and healthy. When the tumour is spread through the healthy tissue, as in the case of metastases, the knowledge of the different kinds of tissues in the sample being analysed is crucial. If the percentage of tumour and normal tissues cannot be evaluated, the obtained concentration is a mean value depending on the composition of the different samples being measured. In this case an imaging method that could give information both on the morphology and on the spatial distribution of boron concentration in the sample would be a fundamental support. In this paper, the results of the boron uptake analysis in the tumour and in the healthy samples taken from human livers after boron phenylalanine (BPA) infusion are shown; boron imaging was performed using neutron autoradiography.

Microwave digestion techniques applied to determination of boron by ICP-AES in BNCT program

International Nuclear Information System (INIS)

Farias, Silvia S.; Di Santo, Norberto R.; Garavaglia, Ricardo N.; Pucci, Gladys N.; Batistoni, Daniel A.; Schwint, Amanda E.

1999-01-01

Recently, boron neutron capture therapy (BNCT) has merged as an interesting option for the treatment of some kind of tumors where established therapies show no success. A molecular boronated species, enriched in 10 B is administrated to the subject; it localizes in malignant tissues depending the kind of tumor and localization. Therefore, a very important fact in BNCT research is the detection of boron at trace or ultra trace levels precisely and accurately. This is extremely necessary as boronated species do localize in tumoral tissue and also localize in liver, kidney, spleen, skin, membranes. By this way, before testing a boronated species, it is mandatory to determine its biodistribution in a statistically meaning population, that is related with managing of a great number of samples. In the other hand, it is necessary to exactly predict when to begin the irradiation and to determine the magnitude of radiation to obtain the desired radiological dose for a specified mean boron concentration. This involves the determination of boron in whole blood, which is related with boron concentration in the tumor object of treatment. The methodology selected for the analysis of boron in whole blood and tissues must join certain characteristics: it must not be dependant of the chemical form of boron, it has to be fast and capable to determine boron accurately and precisely in a wide range of concentrations. The design and validation of experimental models involving animals in BNCT studies and the determination of boron in blood of animals and subjects upon treatment require reliable analytical procedures to determine boron quantitatively in those biologic materials. Inductively coupled plasma-atomic emission spectrometry (ICP-AES) using pneumatic nebulization is one of the most promising methods for boron analysis, but the sample must be liquid and have low solid concentration. In our case, biological tissues and blood, it is mandatory to mineralize and/or dilute samples

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...

Design of thermal neutron beam based on an electron linear accelerator for BNCT.

Science.gov (United States)

Zolfaghari, Mona; Sedaghatizadeh, Mahmood

2016-12-01

An electron linear accelerator (Linac) can be used for boron neutron capture therapy (BNCT) by producing thermal neutron flux. In this study, we used a Varian 2300 C/D Linac and MCNPX.2.6.0 code to simulate an electron-photoneutron source for use in BNCT. In order to decelerate the produced fast neutrons from the photoneutron source, which optimize the thermal neutron flux, a beam-shaping assembly (BSA) was simulated. After simulations, a thermal neutron flux with sharp peak at the beam exit was obtained in the order of 3.09×10 8 n/cm 2 s and 6.19×10 8 n/cm 2 s for uranium and enriched uranium (10%) as electron-photoneutron sources respectively. Also, in-phantom dose analysis indicates that the simulated thermal neutron beam can be used for treatment of shallow skin melanoma in time of about 85.4 and 43.6min for uranium and enriched uranium (10%) respectively. Copyright © 2016. Published by Elsevier Ltd.

Tandem electrostatic accelerators for BNCT

International Nuclear Information System (INIS)

Ma, J.C.

1994-01-01

The development of boron neutron capture therapy (BNCT) into a viable therapeutic modality will depend, in part, on the availability of suitable neutron sources compatible with installation in a hospital environment. Low-energy accelerator-based intense neutron sources, using electrostatic or radio frequency quadrupole proton accelerators have been suggested for this purpose and are underdevelopment at several laboratories. New advances in tandem electrostatic accelerator technology now allow acceleration of the multi-milliampere proton beams required to produce therapeutic neutron fluxes for BNCT. The relatively compact size, low weight and high power efficiency of these machines make them particularly attractive for installation in a clinical or research facility. The authors will describe the limitations on ion beam current and available neutron flux from tandem accelerators relative to the requirements for BNCT research and therapy. Preliminary designs and shielding requirements for a tandern accelerator-based BNCT research facility will also be presented

The Swedish facility for boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Skoeld, K.; Capala, J. [Studsvik Medical AB (Sweden); Kierkegaard, J.; Haakansson, R. [Studsvik Nuclear AB (Sweden); Gudowska, I. [Karolinska Institute (Sweden)

2000-10-01

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

The Swedish facility for boron neutron capture therapy

International Nuclear Information System (INIS)

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

2000-01-01

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

An update on the clinical trial of BNCT at the BMRR

International Nuclear Information System (INIS)

Ma, R.; Capala, J.; Chanana, A.D.; Coderre, J.A.; Diaz, A.Z.

1999-01-01

Boron neutron capture therapy (BNCT) was proposed more than six decades ago. It is a binary treatment modality that requires selective delivery of a 10 B-labeled compound to a tumor and slow neutron irradiation of the tumor-bearing tissues. In order to improve the penetration of the neutron beam, an epithermal neutron beam was developed at the Brookhaven Medical Research Reactor (BMRR). This epithermal neutron beam can deliver relatively high thermal neutron fluence at depth without severe skin damage. Boronophenylalanine-fructose (BPA-F), a nontoxic boron carrier, was found to preferentially accumulate in tumor cells following intravenous infusion in patients with GBM. In preclinical BNCT studies in rats bearing 9L gliosarcoma, BPA-mediated BNCT was shown to be more efficacious than photon irradiation. In 1994, improvements in the neutron beam and in the understanding of the radiobiology of BPA-mediated BNCT led to the initiation of BNCT trials for human GBM at BMRR using BPA-F and epithermal neutrons. The primary objective of the phase I/II clinical trial of BPA-mediated BNCT at BMRR is to evaluate the safety of the BPA-F-mediated BNCT using epithermal neutrons in patients with GBM at a series of escalating BNCT doses. An incidental objective is to evaluate the therapeutic effectiveness of BNCT at each dose level. For each dose escalation group, the average brain dose (ABD) is escalated, as well as the minimum tumor dose. In summary, the BNCT procedure employed in the phase I/II clinical trial of BPA-F-mediated BNCT for GBM at BNL was found to be safe in all patients. The palliation afforded by a single session of BNCT compares favorably with palliation provided by fractionated photon therapy and adjuvant chemotherapy. If no evidence of radiation-induced brain toxicity is found in the current protocol, BNCT radiation dose will be further escalated

INEEL BNCT Research Program Annual Report, CY-2000

Energy Technology Data Exchange (ETDEWEB)

Venhuizen, James Robert

2001-03-01

This report is a summary of the activities conducted in conjunction with the Idaho National Engineering and Environmental Laboratory (INEEL) Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 2000. Applications of supportive research and development, as well as technology deployment in the fields of chemistry, radiation physics and dosimetry, neutron source design and demonstration, and support the Department of Energy’s (DOE) National BNCT Program goals are the goals of this Program. Contributions from the individual contributors about their projects are included, specifically described are the following, chemistry: analysis of biological samples and an infrared blood-boron analyzer, and physics: progress in the patient treatment planning software, measurement of neutron spectra for the Argentina RA-6 reactor, and recalculation of the Finnish research reactor FiR 1 neutron spectra, BNCT accelerator technology, and modification to the research reactor at Washington State University for an epithermal-neutron beam.

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

International Nuclear Information System (INIS)

Mitchell, H.E.

1996-04-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1996-04-01

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

Optimization of beam shaping assembly based on D-T neutron generator and dose evaluation for BNCT

Science.gov (United States)

Naeem, Hamza; Chen, Chaobin; Zheng, Huaqing; Song, Jing

2017-04-01

The feasibility of developing an epithermal neutron beam for a boron neutron capture therapy (BNCT) facility based on a high intensity D-T fusion neutron generator (HINEG) and using the Monte Carlo code SuperMC (Super Monte Carlo simulation program for nuclear and radiation process) is proposed in this study. The Monte Carlo code SuperMC is used to determine and optimize the final configuration of the beam shaping assembly (BSA). The optimal BSA design in a cylindrical geometry which consists of a natural uranium sphere (14 cm) as a neutron multiplier, AlF3 and TiF3 as moderators (20 cm each), Cd (1 mm) as a thermal neutron filter, Bi (5 cm) as a gamma shield, and Pb as a reflector and collimator to guide neutrons towards the exit window. The epithermal neutron beam flux of the proposed model is 5.73 × 109 n/cm2s, and other dosimetric parameters for the BNCT reported by IAEA-TECDOC-1223 have been verified. The phantom dose analysis shows that the designed BSA is accurate, efficient and suitable for BNCT applications. Thus, the Monte Carlo code SuperMC is concluded to be capable of simulating the BSA and the dose calculation for BNCT, and high epithermal flux can be achieved using proposed BSA.

A core laboratory offering full evaluation of new boron compounds. A service to the BNCT community

International Nuclear Information System (INIS)

Zamenhof, R.G.; Patel, H.; Palmer, M.R.; Lin, H.C.; Busse, P.M.; Harling, O.; Binns, P.J.; Riley, K.J.; Bernard, J.

2000-01-01

A joint project by the Beth Israel Deaconess Medical Center at Harvard Medical School and The Nuclear Reactor Laboratory of the Massachusetts Institute of Technology is proposed which would provide a core laboratory for the evaluation of new boron compounds. Federal agency funding has been applied for to support such a facility. The facility's evaluation of candidate boron compounds will include: quantitative cellular boron uptake; cell survival curve analysis (using a thermal neutron beam); small or large animal pharmacokinetic analysis; macro- and micro boron distribution analysis using high-resolution autoradiography, prompt gamma analysis and ICP-AES; small or large animal in vivo tumor control studies (using thermal or epithermal neutron beams); and pharmacological in vivo toxicity evaluation. The laboratory will include small and large animal surgical facilities and resources for additional boron compound chemistry as required by the evaluation procedure. This facility will be open to the BNCT research community. (author)

{sup 124}Sb–Be photo-neutron source for BNCT: Is it possible?

Energy Technology Data Exchange (ETDEWEB)

Golshanian, Mohadeseh [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Department of Physics, Shahrood University, Shahrood (Iran, Islamic Republic of); Rajabi, Ali Akbar [Department of Physics, Shahrood University, Shahrood (Iran, Islamic Republic of); Kasesaz, Yaser, E-mail: ykasesaz@aeoi.org.ir [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of)

2016-11-01

In this research a computational feasibility study has been done on the use of {sup 124}SbBe photo-neutron source for Boron Neutron Capture Therapy (BNCT) using MCNPX Monte Carlo code. For this purpose, a special beam shaping assembly has been designed to provide an appropriate epithermal neutron beam suitable for BNCT. The final result shows that using 150 kCi of {sup 124}Sb, the epithermal neutron flux at the designed beam exit is 0.23×10{sup 9} (n/cm{sup 2} s). In-phantom dose analysis indicates that treatment time for a brain tumor is about 40 min which is a reasonable time. This high activity {sup 124}Sb could be achieved using three 50 kCi rods of {sup 124}Sb which can be produced in a research reactor. It is clear, that as this activity is several hundred times the activity of a typical cobalt radiotherapy source, issues related to handling, safety and security must be addressed.

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

Science.gov (United States)

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

2011-01-01

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

Current status of accelerator-based boron neutron capture therapy

International Nuclear Information System (INIS)

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

2011-01-01

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

INEL BNCT Research Program annual report, 1992

Energy Technology Data Exchange (ETDEWEB)

Venhuizen, J.R. [ed.

1993-05-01

This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1992. Contributions from all the principal investigators about their individual projects are included, specifically, chemistry (pituitary tumor targeting compounds, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis of biological samples), physics (radiation dosimetry software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (small and large animal models tissue studies and efficacy studies). Information on the potential toxicity of borocaptate sodium and boronophenylalanine is presented, results of 21 spontaneous-tumor-bearing dogs that have been treated with BNCT at the Brookhaven National Laboratory (BNL) Medical Research Reactor (BMRR) are discussed, and predictions for an epithermal-neutron beam at the Georgia Tech Research Reactor (GTRR) are shown. Cellular-level boron detection and localization by secondary ion mass spectrometry, sputter-initiated resonance ionization spectroscopy, low atomization resonance ionization spectroscopy, and alpha track are presented. Boron detection by ICP-AES is discussed in detail. Several boron carrying drugs exhibiting good tumor uptake are described. Significant progress in the potential of treating pituitary tumors with BNCT is presented. Measurement of the epithermal-neutron flux at BNL and comparison to predictions are shown. Calculations comparing the GTRR and BMRR epithermal-neutron beams are also presented. Individual progress reports described herein are separately abstracted and indexed for the database.

INEL BNCT Research Program annual report, 1992

International Nuclear Information System (INIS)

Venhuizen, J.R.

1993-05-01

This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1992. Contributions from all the principal investigators about their individual projects are included, specifically, chemistry (pituitary tumor targeting compounds, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis of biological samples), physics (radiation dosimetry software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (small and large animal models tissue studies and efficacy studies). Information on the potential toxicity of borocaptate sodium and boronophenylalanine is presented, results of 21 spontaneous-tumor-bearing dogs that have been treated with BNCT at the Brookhaven National Laboratory (BNL) Medical Research Reactor (BMRR) are discussed, and predictions for an epithermal-neutron beam at the Georgia Tech Research Reactor (GTRR) are shown. Cellular-level boron detection and localization by secondary ion mass spectrometry, sputter-initiated resonance ionization spectroscopy, low atomization resonance ionization spectroscopy, and alpha track are presented. Boron detection by ICP-AES is discussed in detail. Several boron carrying drugs exhibiting good tumor uptake are described. Significant progress in the potential of treating pituitary tumors with BNCT is presented. Measurement of the epithermal-neutron flux at BNL and comparison to predictions are shown. Calculations comparing the GTRR and BMRR epithermal-neutron beams are also presented. Individual progress reports described herein are separately abstracted and indexed for the database

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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.

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

International Nuclear Information System (INIS)

Chadha, M.

1996-01-01

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

Boron neutron capture therapy of intracerebral rat gliosarcomas

International Nuclear Information System (INIS)

Joel, D.D.; Fairchild, R.G.; Laissue, J.A.; Saraf, S.K.; Kalef-Ezra, J.A.; Slatkin, D.N.

1990-01-01

The efficacy of boron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested. Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na4(10)B24H22S2, at a rate of 45-50 micrograms of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0). This infusion schedule resulted in average blood 10B concentrations of 35 micrograms/ml in a group of 12 gliosarcoma-bearing rats and 45 micrograms/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT. Estimated tumor 10B levels in these two groups were 26 and 34 micrograms/g, respectively. On day 14, boron-treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW.min of radiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of approximately 2.0 x 10(12) or approximately 3.0 x 10(12) n/cm2, respectively, in the tumors. Untreated rats had a median postinitiation survival time of 21 days. Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MW.min) or 28 (7.5 MW.min) days. The 12 rats that received 5 MW.min of BNCT had a median postinitiation survival time of 60 days. Two of these animals survived greater than 15 months. In the 7.5 MW.min group, the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after BNCT. The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively. Similar gliosarcoma-bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation

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

International Nuclear Information System (INIS)

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

1986-01-01

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 10 B; (2) Synthesis of 10 B-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 10 B 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

Analysis of accelerator based neutron spectra for BNCT using proton recoil spectroscopy

International Nuclear Information System (INIS)

Wielopolski, L.; Ludewig, H.; Powell, J.R.; Raparia, D.; Alessi, J.G.; Lowenstein, D.I.

1998-01-01

Boron Neutron Capture Therapy (BNCT) is a promising binary treatment modality for high-grade primary brain tumors (glioblastoma multiforme, GM) and other cancers. BNCT employs a boron-10 containing compound that preferentially accumulates in the cancer cells in the brain. Upon neutron capture by 10 B energetic alpha particles and triton released at the absorption site kill the cancer cell. In order to gain penetration depth in the brain Fairchild proposed, for this purpose, the use of energetic epithermal neutrons at about 10 keV. Phase I/II clinical trials of BNCT for GM are underway at the Brookhaven Medical Research Reactor (BMRR) and at the MIT Reactor, using these nuclear reactors as the source for epithermal neutrons. In light of the limitations of new reactor installations, e.g. cost, safety and licensing, and limited capability for modulating the reactor based neutron beam energy spectra alternative neutron sources are being contemplated for wider implementation of this modality in a hospital environment. For example, accelerator based neutron sources offer the possibility of tailoring the neutron beams, in terms of improved depth-dose distributions, to the individual and offer, with relative ease, the capability of modifying the neutron beam energy and port size. In previous work new concepts for compact accelerator/target configuration were published. In this work, using the Van de Graaff accelerator the authors have explored different materials for filtering and reflecting neutron beams produced by irradiating a thick Li target with 1.8 to 2.5 MeV proton beams. However, since the yield and the maximum neutron energy emerging from the Li-7(p,n)Be-7 reaction increase with increase in the proton beam energy, there is a need for optimization of the proton energy versus filter and shielding requirements to obtain the desired epithermal neutron beam. The MCNP-4A computer code was used for the initial design studies that were verified with benchmark experiments

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

International Nuclear Information System (INIS)

Nose, Tadao; Matsumura, Akira; Nakai, Kei; Nakagawa, Kunio; Yoshii, Yoshihiko; 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.)

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.)

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

International Nuclear Information System (INIS)

Yanagie, Hironobu; Takahashi, Hiroyuki

2010-01-01

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

On line local measurement of thermal neutron flux on BNCT patient using SPND

International Nuclear Information System (INIS)

Miller, M.E.; Sztejnberg Goncalves-Carralves, M.L.; Gonzalez, S.J.

2006-01-01

The first on-line neutron flux measurement on a patient using a self-powered neutron detector (SPND) was assessed during the fourth clinical trial of the Boron Neutron Capture Therapy (BNCT) Project carried out at the National Atomic Energy Commission of Argentina (CNEA) and the medical center Angel H. Roffo. The SPND was specially developed and assembled for BNCT by CNEA. Its small size, 1 cm sensible length and 1.9 mm diameter, allowed performing a localized measurement. Since the treated tumors were cutaneous melanomas of nodular type, the SPND was located on the patient's skin. The patient was exposed to three different and consecutive fields and in each of them the SPND was used to measure local thermal neutron fluxes at selected dosimetric reference points. The values of the measured fluxes agreed with the ones estimated by calculation. This trial also demonstrated the usefulness of the SPND for assessing flux on-line. (author)

An accelerator neutron source for BNCT. Technical progress report, 1 June 1993--31 May 1994

International Nuclear Information System (INIS)

Blue, T.E.; Vafai, K.

1994-02-01

This is the progress report for the project entitled, ''An Accelerator Neutron Source for BNCT.'' The progress report is for the period from July 1, 1993 to date. The overall objective of our research project is to develop an Accelerator Epithermal Neutron Irradiation Facility (AENIF) for Boron Neutron Capture Therapy (BNCT). The AENIF consists of a 2.5 MeV high current proton accelerator, a lithium target to produce source neutrons, and a moderator/reflector assembly to obtain from the energetic source neutrons an epithermal neutron field suitable for BNCT treatments. Our project goals are to develop the non-accelerator components of the AENIF, and to specifically include in our development: (1) design, numerical simulation, and experimental verification of a target assembly which is capable of removing 75 kW of beam power; (2) re-optimization of the moderator assembly design based on in-phantom dose assessments using neutron spectra calculated in phantom and an energy-dependent neutron Relative Biological Effectiveness (RBE); (3) construction of a prototype moderator assembly and confirmation of its design by measurements; (4) design of the shielding of the accelerator and treatment rooms for an AENIF; and (5) design of a high energy beam transport system which is compatible with the shielding design and the thermal-hydraulic design

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

International Nuclear Information System (INIS)

Moss, R.L.

2004-01-01

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

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

International Nuclear Information System (INIS)

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

1994-01-01

The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report

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.

Conceptual design of 30 MeV magnet system used for BNCT epithermal neutron source

International Nuclear Information System (INIS)

Slamet Santosa; Taufik

2015-01-01

Conceptual design of 30 MeV Magnet System Used for BNCT Epithermal Neutron Source has been done based on methods of empirical model of basic equation, experiences of 13 MeV cyclotron magnet design and personal communications. In the field of health, cyclotron can be used as an epithermal neutron source for Boron Neutron Capture Therapy (BNCT). The development of cyclotron producing epithermal neutrons for BNCT has been performed at Kyoto University, of which it produces a proton beam current of 1.1 mA with energy of 30 MeV. With some experiences on 13 MeV cyclotron magnet design, to support BNCT research and development we performed the design studies of 30 MeV cyclotron magnet system, which is one of the main components of the cyclotron for deflecting proton beam into circular trajectory and serves as beam focusing. Results of this study are expected to define the parameters of particular cyclotron magnet. The scope of this study includes the study of the parameters component of the 30 MeV cyclotron and magnet initial parameters. The empirical method of basic equation model is then corroborated by a simulation using Superfish software. Based on the results, a 30 MeV cyclotron magnet for BNCT neutron source enables to be realized with the parameters of B 0 = 1.06 T, frequency RF = 64.733938 ≈ 65 MHz, the external radius of 0.73 m, the radius of the polar = 0.85 m, BH = 1.95 T and a gap hill of 4 cm. Because proton beam current that be needed for BNCT application is very large, then in the calculation it is chosen a great focusing axial νz = 0.630361 which can generate B V = 0.44 T. (author)

Boron neutron capture therapy: Brain Tumor Treatment Evaluation Program

International Nuclear Information System (INIS)

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

1988-01-01

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

2-O-α-glucopytanosyl L-ascorbic acid reduced mutagenicity at HPRT locus of mouse splenocytes following BNCT

International Nuclear Information System (INIS)

Kinashi, Yuko; Masunaga, Shin-ichiro; Suzuki, Minoru; Nagata, Kanji; Ono, Koji

2006-01-01

In boron neutron capture therapy (BNCT), normal tissue surrounding the tumor cells sometimes take up boron compounds resulting in radiation-induced damage to normal tissue. We have previously reported the evidence for increased the mutagenicity of thermal neutron in the presence of boron. In addition, we described the biological radio-protective effects of the ascorbic acid for mutation induction following BNCT in vitro. Here, we investigated these radio-protective effects of ascorbic acid for mutation induction in mouse splenocytes on HPRT locus following a BNCT study in vivo. (author)

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.

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

International Nuclear Information System (INIS)

Nigg, D.W.

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.

A new target concept for proton accelerator driven boron neutron capture therapy applications

International Nuclear Information System (INIS)

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

1998-01-01

A new target concept termed Discs Incorporating Sector Configured Orbiting Sources (DISCOS), is proposed for spallation applications, including BNCT (Boron Neutron Capture Therapy). In the BNCT application a proton beam impacts a sequence of ultra thin lithium DISCOS targets to generate neutrons by the 7 Li(p,n) 7 Be reaction. The proton beam loses only a few keV of its ∼MeV energy as it passes through a given target, and is re-accelerated to its initial energy, by a DC electric field between the targets

Commercial Clinical Application of Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

1999-01-01

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

Feasibility of the utilization of BNCT in the fast neutron therapy beam at Fermilab

International Nuclear Information System (INIS)

Langen, Katja; Lennox, Arlene J.; Kroc, Thomas K.; DeLuca, Paul M. Jr.

2000-01-01

The Neutron Therapy Facility at Fermilab has treated cancer patients since 1976. Since then more than 2,300 patients have been treated and a wealth of clinical information accumulated. The therapeutic neutron beam at Fermilab is produced by bombarding a beryllium target with 66 MeV protons. The resulting continuous neutron spectrum ranges from thermal to 66 MeV in neutron energy. It is clear that this spectrum is not well suited for the treatment of tumors with boron neutron capture therapy (BNCT) only However, since this spectrum contains thermal and epithermal components the authors are investigating whether BNCT can be used in this beam to boost the tumor dose. There are clinical scenarios in which a selective tumor dose boost of 10 - 15% could be clinically significant. For these cases the principal treatment would still be fast neutron therapy but a tumor boost could be used either to deliver a higher dose to the tumor tissue or to reduce the dose to the normal healthy tissue while maintaining the absorbed dose level in the tumor tissue

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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.

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

Energy Technology Data Exchange (ETDEWEB)

Bortolussi, S.; Stella, S.; De Bari, A.; Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy)]|[National Institute of Nuclear Physics (INFN), Pavia (Italy); Bruschi, P.; Bakeine, J.G. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Clerici, A.; Ferrari, C.; Zonta, C.; Zonta, A. [Department of Surgery, University of Pavia, Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, Pavia (Italy)

2008-10-29

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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

Science.gov (United States)

Blue, Thomas E; Yanch, Jacquelyn C

2003-01-01

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

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

International Nuclear Information System (INIS)

Monti Hughes, Andrea; Trivillin, Veronica A.; Schwint, Amanda E.; Longhino, Juan; Boggio, Esteban; Medina, Vanina A.; Martinel Lamas, Diego J.; Garabalino, Marcela A.; Heber, Elisa M.; Pozzi, Emiliano C.C.; Itoiz, Maria E.; Aromando, Romina F.; Nigg, David W.

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-11-15

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

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)

Moss, R.L.; Rassow, J.; Finke, E.; Sauerwein, W.; Stecher-Rasmussen, F.

2001-01-01

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)

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

International Nuclear Information System (INIS)

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

2001-01-01

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

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

International Nuclear Information System (INIS)

Yamada, Yoshihiko; Ichihashi, Masamitsu; Kahl, S.B.; Toda, Ken-ichi.

1994-01-01

We have already achieved successful treatment of several human patients with malignant melanoma by boron neutron capture therapy (BNCT) using 10 B 1 -paraboronophenylalanine ( 10 B 1 -BPA·HCl). In this study we used a new compound, a manganese boronated protoporphyrin (Mn- 10 BOPP), and compared it to 10 B 1 -BPA·HCl with respect to uptake in murine melanoma and angiosarcoma cells as well as to their cell killing effect. 10 B uptake was measured in a new method, and the new compound was much more incorporated into both cells than 10 B 1 -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 10 B 1 -BPA·HCl. (author)

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

International Nuclear Information System (INIS)

Hatanaka, Hiroshi

1993-01-01

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

In vitro biological models in order to study BNCT

International Nuclear Information System (INIS)

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

1999-01-01

Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of 10 B-boronated compounds by some tumours, followed by irradiation with an appropriate neutron beam. The radioactive boron originated ( 11 B) decays releasing 7 Li, gamma rays and alpha particles, and these latter will destroy the tumour. In order to explore the possibility of applying BNCT to UTC we have studied the biodistribution of BPA. In vitro studies: the uptake of p- 10 borophenylalanine (BPA) by the UTC cell line ARO, primary cultures of normal bovine thyroid cells (BT) and human follicular adenoma (FA) thyroid was studied. No difference in BPA uptake was observed between proliferating and quiescent ARO cells. The uptake by quiescent ARO, BT and FA showed that the ARO/BT and ARO/FA ratios were 4 and 5, respectively (p< 0.001). The present experimental results open the possibility of applying BNCT for the treatment of UTC. (author)

Boron neutron capture therapy for malignant brain tumor in Japan

Energy Technology Data Exchange (ETDEWEB)

Nakagawa, Yoshinobu [National Kagawa Children`s Hospital, Takamatsu, Kagawa (Japan)

1998-03-01

Since 1968, we have treated 149 patients and performed boron-neutron capture therapy (BNCT) on 164 occasions using 5 reactors in Japan. There were 64 patients with glioblastoma, 39 patients with anaplastic astrocytoma and 17 patients with low grade astrocytoma (grade 1 or 2). There were 30 patients with other types of tumor. The overall response rate in the glioma patients was 64%. Seven patients (12%) of glioblastoma, 22 patients (56%) of anaplastic astrocytoma and 8 patients (62%) of low grade astrocytoma lived more than 2 years Median survival time of glioblastoma was 640 days. Median survival times of patients with anaplastic astrocytoma was 1811 days, and 1669 days in low grade astrocytoma. Six patients (5 glioblastoma and one anaplastic astrocytoma) died within 90 days after BNCT. Six patients lived more than 10 years. Histological grading, age of the patients, neutron fluence at the target point and target depth or size of the tumor were proved to be important factors. BNCT is an effective treatment for malignant brain tumors. We are now became able to radiate the tumor more correctly with a high enough dose of neutron beam even if we use thermal neutron beam. (author)

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

Summaries on various researches aiming at the closed head BNCT

International Nuclear Information System (INIS)

Ono, Koji

2000-01-01

As in the boron neutron capture therapy (BNCT) flight of alpha particle formed by reaction of neutron and boron is nearly equal to diameter of cancer cell, when a boron compound accumulates selectively to a cancer cell to be radiated onto the cell by enough amount of neutron beam the alpha particles are irradiated onto the cancer cells nearly selectively. Like this, this is a curing means capable of overcoming a problem undecidable by a paradigm of radiation remedy in the 20th Century, a micro dose amount effect supposing to be a paradigm in the 21st Century, the very (biological) dose concentration into cancer cell is a curing method matching to upgrading on rate of cancer control and improvement on post-cure of the patients without increase of subreaction in every tumors. Here were summarized on characteristic comparison of thermal outer-neutron beams in KUR, JRR-4 and the Peten HFR reactors, development of new boron compounds, effect of BNCT on re-oxygenation of the cancer, and induction of mutation by neutron beam. (G.K.)

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

Directory of Open Access Journals (Sweden)

Muhammad Mu’Alim

2018-01-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Implementation of BNCT treatment planning procedures

International Nuclear Information System (INIS)

Capala, J.; Ma, R.; Diaz, A.Z.; Chanana, A.D.; Coderre, J.A.

2001-01-01

Estimation of radiation doses delivered during boron neutron capture therapy (BNCT) requires combining data on spatial distribution of both the thermal neutron fluence and the 10 B concentration, as well as the relative biological effectiveness of various radiation dose components in the tumor and normal tissues. Using the treatment planning system created at Idaho National Engineering and Environmental Laboratory and the procedures we had developed for clinical trials, we were able to optimize the treatment position, safely deliver the prescribed BNCT doses, and carry out retrospective analyses and reviews. In this paper we describe the BNCT treatment planning process and its implementation in the ongoing dose escalation trials at Brookhaven National Laboratory. (author)

A parameter study to determine the optimal source neutron energy in boron neutron capture therapy of brain tumours

Energy Technology Data Exchange (ETDEWEB)

Nievaart, V A [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Moss, R L [Joint Research Centre of the European Commission, Postbus 2, 1755ZG Petten (Netherlands); Kloosterman, J L [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Hagen, T H J J van der [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Dam, H van [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands)

2004-09-21

The values of the parameters used in boron neutron capture therapy (BNCT) to calculate a given dose to human tissue vary with patients due to different physical, biological and/or medical circumstances. Parameters include the tissue dimensions, the {sup 10}B concentration and the relative biological effectiveness (RBE) factors for the different dose components associated with BNCT. Because there is still no worldwide agreement on RBE values, more often than not, average values for these parameters are used. It turns out that the RBE-problem can be circumvented by taking into account all imaginable parameter values. Approaching this quest from another angle: the outcome will also provide the parameters (and values) which influence the optimal source neutron energy. For brain tumours it turns out that the {sup 10}B concentration, the RBE factors for {sup 10}B as well as fast neutrons, together with the dose limit set for healthy tissue, affect the optimal BNCT source neutron energy. By using source neutrons of a few keV together with neutrons of a few eV, it ensures that, under all imaginable circumstances, a maximum of alpha (and lithium) particles can be delivered in the tumour.

Spectrum shaping assessment of accelerator-based fusion neutron sources to be used in BNCT treatment

Science.gov (United States)

Cerullo, N.; Esposito, J.; Daquino, G. G.

2004-01-01

Monte Carlo modelling of an irradiation facility, for boron neutron capture therapy (BNCT) application, using a set of advanced type, accelerator based, 3H(d,n) 4He (D-T) fusion neutron source device is presented. Some general issues concerning the design of a proper irradiation beam shaping assembly, based on very hard energy neutron source spectrum, are reviewed. The facility here proposed, which represents an interesting solution compared to the much more investigated Li or Be based accelerator driven neutron source could fulfil all the medical and safety requirements to be used by an hospital environment.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

Neutron field characterization in the installation for BNCT study in the IEA-R1 reactor; Caracterizacao do campo de neutrons na instalacao para estudo em BNCT no reator IEA-R1

Energy Technology Data Exchange (ETDEWEB)

Carneiro Junior, Valdeci

2008-07-01

This work aims to characterize the mixed neutron and gamma field, in the sample irradiation position, in a research installation for Boron Neutron Capture Therapy (BNCT), in the IPEN IEA-R1 reactor. The BNCT technique has been studied as a safe and selective option in the treatment of resistant cancerigenous tumors or considered non-curable by the conventional techniques, for example, the Glioblastoma Multiform - a brain cancerigenous tumor. Neutron flux measurements were carried out: thermal, resonance and fast, as well as neutron and gamma rays doses, in the sample position, using activation foils detectors and thermoluminescent dosimeters. For the determination of the neutron spectrum and intensity, a set of different threshold activation foils and gold foils covered and uncovered with cadmium irradiated in the installation was used, analyzed by a high Pure Germanium semiconductor detector, coupled to an electronic system suitable for gamma spectrometry. The results were processed with the SAND-BP code. The doses due to gamma and neutron rays were determined using thermoluminescent dosimeters TLD 400 and TLD 700 sensitive to gamma and TLD 600, sensitive to neutrons. The TLDs were selected and used for obtaining the calibration curves - dosimeter answer versus dose - from each of the TLD three types, which were necessary to calculate the doses due to neutron and gamma, in the sample position. The radiation field, in the sample irradiation position, was characterized flux for thermal neutrons of 1.39.10{sup 8} {+-} 0,12.10{sup 8} n/cm{sup 2}s the doses due to thermal neutrons are three times higher than those due to gamma radiation and confirm the reproducibility and consistency of the experimental findings obtained. Considering these results, the neutron field and gamma radiation showed to be appropriated for research in BNCT. (author)

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

International Nuclear Information System (INIS)

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

2002-01-01

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 10 B(n,a) 7 Li reaction products is very short, 10-14 μm 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 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 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)

{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.

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

International Nuclear Information System (INIS)

Burns, T.D. Jr.

1995-05-01

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

Synthesis and evaluation of boronated folates for BNCT

International Nuclear Information System (INIS)

Shukla, S.; Sekido, M.; Guo, W.; Mueller, R.; Sudimack, J.; Lee, R.J.; Tjarks, W.; Adams, D.M.; Barth, R.F.

2000-01-01

To study the possible utilization of folic acid as the 10 B carrier for BNCT, folic acid conjugated boron containing liposomes and starburst dendrimers were prepared. In both systems folic acid was used as the recognition part and polyethylene glycol (PEG) as the spacer. In vitro studies were carried out using folate receptor overexpressing 24JK-FBP and KB cells. The results indicated that these boronated folic acid conjugates were incorporated into the tumor cells via receptor-mediated endocytosis. (author)

Radiobiology studies for the evaluation of epithermal neutron beams used for BNCT

International Nuclear Information System (INIS)

Green, S.; Jones, B.; Mill, A.J.

2006-01-01

This paper outlines our plans for a study to establish the radiobiological effectiveness of the various mixes of radiation components present in an epithermal neutron beam designed for BNCT and to incorporate these data into clinical protocols for the treatment of malignant glioma. This is a description of work which is funded and just now beginning in Birmingham so no results can be presented. Our project will involve a combination of experimental measurements carried out in Birmingham and in Boston and mathematical modelling carried out in Birmingham. Despite all the extant in-vitro and in-vivo work, there is no widely accepted method to determine biological effect by accounting for variations in beam component mix, dose rate and treatment fractionation for disparate from the various BNCT centres. The objectives of this study are: To develop a cell-based radiobiology protocol to provide essential data on safety and efficacy of beams for Boron Neutron Capture Therapy (BNCT) in advance of clinical trials. To exploit the facilities at Massachusetts Institute of Technology for variable dose-rate epithermal irradiations to validate the above protocol. To develop mathematical models of this radiobiological system that can be used to inform decisions on dose selection, fractionation schedules, BNCT use as supplementary boosts or for re-treatment of recurrent cancers. To provide fundamental data relevant to the understanding of the radiobiology of simultaneous mixed high-and low-LET radiations over a clinically relevant dose-range. (author)

Medical aspects of boron-slow neutron capture therapy

International Nuclear Information System (INIS)

Sweet, W.H.

1986-01-01

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

Hyaluronic acid as a potential boron carrier for BNCT: Preliminary evaluation

International Nuclear Information System (INIS)

Zaboronok, A.; Yamamoto, T.; Nakai, K.; Yoshida, F.; Uspenskii, S.; Selyanin, M.; Zelenetskii, A.; Matsumura, Akira

2015-01-01

Hyaluronic acid (HA), a nonimmunogenic, biocompatible polymer found in different biological tissues, has the potential to attach to CD44 receptors on the surface of certain cancer cells, where the receptor is overexpressed compared with normal cells. Boron–hyaluronic acid (BHA) was tested for its feasibility as a potential agent for BNCT. BHA with low-viscosity 30 kDa HA could be administered by intravenous injection. The compound showed a certain degree of cytotoxicity and accumulation in C6 rat glioma cells in vitro. Instability of the chelate bonds between boron and HA and/or insufficient specificity of CD44 receptors on C6 cells to BHA could account for the insufficient in vitro accumulation. To ensure the future eligibility of BHA for BNCT experiments, using alternative tumor cell lines and chemically securing the chelate bonds or synthesizing BHA with boron covalently attached to HA might be required. - Highlights: • Hyaluronic acid (HA) is a nonimmunogenic, biocompatible polymer. • Boron–HA (BHA) acid can contain a large number of boron atoms for BNCT. • Active targeting can be realized with CD44 and other HA receptors on tumor cells. • BHA showed a certain degree of toxicity against C6 tumor cells and V79 fibroblasts. • BHA was injected into rats via the tail vein, boron was detected in tumors in vivo.

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

International Nuclear Information System (INIS)

Hawthorne, M. Frederick

2005-01-01

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

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

Science.gov (United States)

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

2014-06-01

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

Clinical practice in BNCT to the brain

International Nuclear Information System (INIS)

Nakagawa, Y.

2001-01-01

Our concept of Boron Neutron Capture Therapy (BNCT) is to selectively destroy tumour cells using the high LET particles yielded from the 10B(n,α)7Li reactions. The effort of clinical investigators has concentrated on how to escalate the radiation dose at the target point. BNCT in Japan combines thermal neutrons and BSH (Na 2 B 12 H 11 SH). The radiation dose is determined by the neutron fluence at the target point and the boron concentration in the tumour tissue. According to the recent analysis, the ratio of boron concentration (BSH) in tumour tissue and blood is nearly stable at around 1.2 to 1.69. Escalation of the radiation dose was carried out by means of improving the penetration of the thermal neutron beam. Since 1968, 175 patients with glioblastoma (n=83), anaplastic astrocytoma (n=44), low grade astrocytoma (n=16) or other types of tumour (n=32) were treated by BNCT at 5 reactors (HTR n=13, JRR-3 n=1, MulTR n=98, KUR n=30, JRR-2 n=33). The retrospective analysis revealed that the important factors related to the clinical results and QOL of the patients were minimum tumour volume radiation dose, more than 18Gy of physical dose and maximum vascular radiation dose (less than 15Gy) in the normal cortex. We have planned several trials to escalate the target radiation dose. One trial makes use of a cavity in the cortex following debulking surgery of the tumour tissue to improve neutron penetration. The other trial is introduction of epithermal neutron. KUR and JRR-4 were reconstructed and developed to be able to irradiate using epithermal neutrons. The new combination of surgical procedure and irradiation using epithermal neutrons should remarkably improve the target volume dose compared to the radiation dose treated by thermal neutrons. (author)

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

Directory of Open Access Journals (Sweden)

Bemby Yulio Vallenry

2015-03-01

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

INEL BNCT Program

International Nuclear Information System (INIS)

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

1991-03-01

This Bulletin presents a summary of accomplishments and highlights in the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program for March 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, a milestone summary, and animal data charts

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

International Nuclear Information System (INIS)

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

1990-01-01

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

Boron neutron capture therapy for malignant brain tumor and future potential

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Hatanaka, Hiroshi.

1994-01-01

This paper presents therapeutic experience with boron neutron capture therapy (BNCT) for malignant brain tumors. Nine patients who survived for 10 years or more as of 1986 are given in a table. A review of the 9 patients concluded that physical dose of 15 Gy is required. In addition, the following factors are defined to be the most important: (1) to determine tumor size and depth as accurately as possible, (2) to measure neutron doses in the deepest site of the tumor during irradiation, (3) to measure the content of boron within the tumor, and to deliver neutron beams as deeply as possible. Finally, the importance of knowing RBE of alpha particles for tumor cells of the human brain is emphasized. (N.K.)

Monitoring total boron in blood for BNCT by a novel atomic emission method

International Nuclear Information System (INIS)

Laakso, J.; Kulvik, M.; Ruokonen, I.; Vaehaetalo, J.; Faerkkilae, M.; Kallio, M.; Zilliacus, R.

2000-01-01

In BNCT the duration and timing of the is adjusted by 10 B concentrations in whole blood. Time-frame for determinations is less than 20 minutes. Therefore fast and accurate boron determinations are a prerequisite for BNCT. We present a method based on ICP-AES instrument for whole blood and plasma boron determinations with protein precipitation with trichloroacetic acid as sample pre-treatment and beryllium as an internal standard. The method was compared to established but tedious ICP-mass spectrometric method with wet ashing as a sample pre-treatment. The ICP-AES method is in good agreement (correlation coefficient 0.99) the ICP-MS. Within-day and between-day imprecisions were less than 3,5% CV for whole blood samples. Samples taken during and after BPA-F infusion (290 mg/kg) revealed an uneven distribution between plasma and erythrocytes. The present method is feasible and one of the fastest currently available for BNCT. Our results indicate that BPA-F or its metabolites do not seem to be tightly bound to plasma proteins. It also seems that determination of boron in plasma sample may be preferable than measuring boron in whole blood. (author)

Microwave digestion techniques applied to determination of boron by ICP-AES in BNCT program; Digestion de matrices biologicas asistida por microondas para el analisis espectrometrico de boro en BNCT

Energy Technology Data Exchange (ETDEWEB)

Farias, Silvia S; Di Santo, Norberto R; Garavaglia, Ricardo N; Pucci, Gladys N; Batistoni, Daniel A [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Quimica; Schwint, Amanda E [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Radiobiologia

1999-07-01

Recently, boron neutron capture therapy (BNCT) has merged as an interesting option for the treatment of some kind of tumors where established therapies show no success. A molecular boronated species, enriched in {sup 10}B is administrated to the subject; it localizes in malignant tissues depending the kind of tumor and localization. Therefore, a very important fact in BNCT research is the detection of boron at trace or ultra trace levels precisely and accurately. This is extremely necessary as boronated species do localize in tumoral tissue and also localize in liver, kidney, spleen, skin, membranes. By this way, before testing a boronated species, it is mandatory to determine its biodistribution in a statistically meaning population, that is related with managing of a great number of samples. In the other hand, it is necessary to exactly predict when to begin the irradiation and to determine the magnitude of radiation to obtain the desired radiological dose for a specified mean boron concentration. This involves the determination of boron in whole blood, which is related with boron concentration in the tumor object of treatment. The methodology selected for the analysis of boron in whole blood and tissues must join certain characteristics: it must not be dependant of the chemical form of boron, it has to be fast and capable to determine boron accurately and precisely in a wide range of concentrations. The design and validation of experimental models involving animals in BNCT studies and the determination of boron in blood of animals and subjects upon treatment require reliable analytical procedures to determine boron quantitatively in those biologic materials. Inductively coupled plasma-atomic emission spectrometry (ICP-AES) using pneumatic nebulization is one of the most promising methods for boron analysis, but the sample must be liquid and have low solid concentration. In our case, biological tissues and blood, it is mandatory to mineralize and/or dilute

INEL BNCT Program

Energy Technology Data Exchange (ETDEWEB)

Ackermann, A.L. (ed.)

1991-08-01

This Bulletin presents a summary of accomplishments and highlights in the Idaho National Engineering Laboratory's (INEL) Boron Neutron Capture Therapy (BNCT) Program for August 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, and updates to the animal data charts.

A sensitivity study on neutron flux variation due to 10B concentration in dose calculation for BNCT

International Nuclear Information System (INIS)

Jung, Sang Hoon

2006-02-01

The effects of inclusion of 10 B concentration on neutron flux and dose in dose calculation were studied. In order to provide the quantitative effects of inclusion of 10 B concentrations on depressions of neutron and photon flux and dose, the fluxes and doses with voxel head phantoms for various 10 B concentrations homogeneously distributed were calculated by using MCNPX simulations. A lithium target system and beam shaping assembly, which have been developed at the Hanyang University, were used as epithermal neutron beam. The calculation results show that the neutron flux at the center of the head phantom decreases by approximately 5.4% per 10 ppm of 10 B concentration in comparison with the neutron flux in the case of boron-free. It was also observed that the tissue dose at the center of the head phantom is depressed by approximately 4.7% per 10 ppm of the 10 B concentration and the tumor dose by approximately 5.3% per 10 ppm. According to depth of tumors, it was observed that the depressions of the doses in the tumors are ranged in 3.7 ∼ 9.2%. The dose calculations in the case of boron-free show that it is overestimated in comparison with the dose calculations in the cases of the inclusion of 10 B concentrations for the normal tissue and the tumors. Therefore, in dose calculation for BNCT, the depressions of neutron flux and dose should be considered. The results in this study are available to setting up the depression ratios which can be used for converting neutron and gamma fluxes and doses in phantom with boron free into the fluxes and doses in phantom with inclusion of 10 B concentrations in treatment. It is expected that the depression ratios is practicable to dose evaluation for BNCT

Boron neutron capture therapy for children with malignant brain tumor

International Nuclear Information System (INIS)

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

1993-01-01

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

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

International Nuclear Information System (INIS)

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

2003-01-01

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

Demonstration of the importance of a dedicated neutron beam monitoring system for BNCT facility

International Nuclear Information System (INIS)

Chao, Der-Sheng; Liu, Yuan-Hao; Jiang, Shiang-Huei

2016-01-01

The neutron beam monitoring system is indispensable to BNCT facility in order to achieve an accurate patient dose delivery. The neutron beam monitoring of a reactor-based BNCT (RB-BNCT) facility can be implemented through the instrumentation and control system of a reactor provided that the reactor power level remains constant during reactor operation. However, since the neutron flux in reactor core is highly correlative to complicated reactor kinetics resulting from such as fuel depletion, poison production, and control blade movement, some extent of variation may occur in the spatial distribution of neutron flux in reactor core. Therefore, a dedicated neutron beam monitoring system is needed to be installed in the vicinity of the beam path close to the beam exit of the RB-BNCT facility, where it can measure the BNCT beam intensity as closely as possible and be free from the influence of the objects present around the beam exit. In this study, in order to demonstrate the importance of a dedicated BNCT neutron beam monitoring system, the signals originating from the two in-core neutron detectors installed at THOR were extracted and compared with the three dedicated neutron beam monitors of the THOR BNCT facility. The correlation of the readings between the in-core neutron detectors and the BNCT neutron beam monitors was established to evaluate the improvable quality of the beam intensity measurement inferred by the in-core neutron detectors. In 29 sampled intervals within 16 days of measurement, the fluctuations in the mean value of the normalized ratios between readings of the three BNCT neutron beam monitors lay within 0.2%. However, the normalized ratios of readings of the two in-core neutron detectors to one of the BNCT neutron beam monitors show great fluctuations of 5.9% and 17.5%, respectively. - Highlights: • Two in-core neutron detectors and three BNCT neutron beam monitors were compared. • BNCT neutron beam monitors improve the stability in neutron

Bystander effect-induced mutagenicity in HPRT locus of CHO cells following BNCT neutron irradiation: Characteristics of point mutations by sequence analysis

Energy Technology Data Exchange (ETDEWEB)

Kinashi, Yuko [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka (Japan)], E-mail: kinashi@rri.kyoto-u.ac.jp; Suzuki, Minoru; Masunaga, Shinichiro; Ono, Koji [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka (Japan)

2009-07-15

To investigate bystander mutagenic effects induced by alpha particles during boron neutron capture therapy (BNCT), we mixed cells that were electroporated with borocaptate sodium (BSH), which led to the accumulation of {sup 10}B inside the cells, with cells that did not contain the boron compound. BSH-containing cells were irradiated with {alpha} particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction, whereas cells without boron were only affected by the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. The frequency of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus was examined in Chinese hamster ovary (CHO) cells irradiated with neutrons (Kyoto University Research Reactor: 5 MW). Neutron irradiation of 1:1 mixtures of cells with and without BSH resulted in a survival fraction of 0.1, and the cells that did not contain BSH made up 99.4% of the surviving cell population. Using multiplex polymerase chain reactions (PCRs), molecular structural analysis indicated that most of the mutations induced by the bystander effect were point mutations and that the frequencies of total and partial deletions induced by the bystander effect were lower than those resulting from the {alpha} particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction or the neutron beam from the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. The types of point mutations induced by the BNCT bystander effect were analyzed by cloning and sequencing methods. These mutations were comprised of 65.5% base substitutions, 27.5% deletions, and 7.0% insertions. Sequence analysis of base substitutions showed that transversions and transitions occurred in 64.7% and 35.3% of cases, respectively. G:C{yields}T:A transversion induced by 8-oxo-guanine in DNA occurred in 5.9% of base substitution mutants in the BNCT bystander group. The characteristic mutations seen in this group, induced by BNCT {alpha} particles

Dose prescription in boron neutron capture therapy

International Nuclear Information System (INIS)

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

1994-01-01

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

In vitro studies of the cellular response to boron neutron capture therapy (BNCT) in thyroid carcinoma

International Nuclear Information System (INIS)

Rodriguez, C; Carpano, M; Perona, M; Thorp, S; Curotto, P; Pozzi, E; Casal, M; Juvenal, G; Pisarev, M; Dagrosa, A

2012-01-01

Background: Previously, we have started to study the mechanisms of DNA damage and repair induced by BNCT in thyroid carcinoma some years ago. We have shown different genotoxic patterns for tumor cells irradiated with gamma rays, neutrons alone or neutrons plus different compounds, boronophenylalanine (BPA) or α, β - dihydroxyethyl)-deutero-porphyrin IX (BOPP). In the present study we analyzed the expression of Ku70, Rad51 and Rad54 components of non homologous end-joing (NHEJ) and homologous recombination repair (HRR) pathways, respectively, induced by BNCT in human cells of thyroid carcinoma. Methods: A human cell line of follicular thyroid carcinoma (WRO) in exponential growth phase was distributed into the following groups: 1) Gamma Radiation, 2) Radiation with neutrons beam (NCT), 3) Radiation with n th in presence of BPA (BNCT). A control group for each treatment was added. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux= 1.10 10 n/cm 2 sec) or with a source of 60 Co. The irradiations were performed during different lapses in order to obtain a total physical dose of 3 Gy (±10%). The mRNA expressions of Ku70, Rad 51 and Rad 54 were analysed by reverse transcription-polymerase chain reaction (RT-PCR) at different times post irradiation (2, 4, 6, 24 and 48 h). DNA damage was evaluated by immunofluorescence using an antibody against the phosphorylation of histone H2AX, which indicates double strand breaks in the DNA. Results: The expression of Rad51 increased at 2 h post-irradiation and it lasted until 6 h only in the neutron and neutron + BPA groups (p<0.05). Rad54 showed an up-regulation from 2 to 24 h in both groups irradiated with the neutron beam (with and without BPA) (p<0.05). On the other hand, Ku70 mRNA did not show a modification of its expression in the irradiated groups respect to the control group. Conclusion: these results would indicate an activation of the HRR pathway in the thyroid carcinoma cells treated by

Investigation of dose distribution in mixed neutron-gamma field of boron neutron capture therapy using N isopropylacrylamide gel

Energy Technology Data Exchange (ETDEWEB)

Bavarmegin, Elham; Sadremomtaz, Alireza [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Khalafi, Hossein; Kasesaz, Yaser [Dept. of Physics, University of Guilan, Rasht (Iran, Islamic Republic of); Khajeali, Azim [Medical Education Research Center, Tabriz (Iran, Islamic Republic of)

2017-02-15

Gel dosimeters have unique advantages in comparison with other dosimeters. Until now, these gels have been used in different radiotherapy techniques as a reliable dosimetric tool. Because dose distribution measurement is an important factor for appropriate treatment planning in different radiotherapy techniques, in this study, we evaluated the ability of the N-isopropylacrylamide (NIPAM) polymer gel to record the dose distribution resulting from the mixed neutron-gamma field of boron neutron capture therapy (BNCT). In this regard, a head phantom containing NIPAM gel was irradiated using the Tehran Research Reactor BNCT beam line, and then by a magnetic resonance scanner. Eventually, the R2 maps were obtained in different slices of the phantom by analyzing T2-weighted images. The results show that NIPAM gel has a suitable potential for recording three-dimensional dose distribution in mixed neutron-gamma field dosimetry.

A comparison of the COG and MCNP codes in computational neutron capture therapy modeling, Part I: boron neutron capture therapy models.

Science.gov (United States)

Culbertson, C N; Wangerin, K; Ghandourah, E; Jevremovic, T

2005-08-01

The goal of this study was to evaluate the COG Monte Carlo radiation transport code, developed and tested by Lawrence Livermore National Laboratory, for neutron capture therapy related modeling. A boron neutron capture therapy model was analyzed comparing COG calculational results to results from the widely used MCNP4B (Monte Carlo N-Particle) transport code. The approach for computing neutron fluence rate and each dose component relevant in boron neutron capture therapy is described, and calculated values are shown in detail. The differences between the COG and MCNP predictions are qualified and quantified. The differences are generally small and suggest that the COG code can be applied for BNCT research related problems.

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

International Nuclear Information System (INIS)

Ariyoshi, Yasunori; Shimahara, Masashi; Kimura, Yoshihiro; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Nagata, Kenji; Sakurai, Yoshinori; Maruhashi, Akira; Ono, Koji

2006-01-01

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 10 B-carrier p-boronophenylalanine (BPA) with or without borocaptate sodium (BSH) and irradiation thereafter with epithermal neutrons. All underwent 18 F-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)

INEEL BNCT research program. Annual report, January 1, 1996--December 31, 1996

International Nuclear Information System (INIS)

Venhuizen, J.R.

1997-04-01

This report is a summary of the progress and research produced for the Idaho National Engineering and Environmental Laboratory (INEEL) Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1996. Contributions from the individual investigators about their projects are included, specifically, physics: treatment planning software, real-time neutron beam measurement dosimetry, measurement of the Finnish research reactor epithermal neutron spectrum, BNCT accelerator technology; and chemistry: analysis of biological samples and preparation of 10 B enriched decaborane

Neutron field characterization in the installation for BNCT study in the IEA-R1 reactor

International Nuclear Information System (INIS)

Carneiro Junior, Valdeci

2008-01-01

This work aims to characterize the mixed neutron and gamma field, in the sample irradiation position, in a research installation for Boron Neutron Capture Therapy (BNCT), in the IPEN IEA-R1 reactor. The BNCT technique has been studied as a safe and selective option in the treatment of resistant cancerigenous tumors or considered non-curable by the conventional techniques, for example, the Glioblastoma Multiform - a brain cancerigenous tumor. Neutron flux measurements were carried out: thermal, resonance and fast, as well as neutron and gamma rays doses, in the sample position, using activation foils detectors and thermoluminescent dosimeters. For the determination of the neutron spectrum and intensity, a set of different threshold activation foils and gold foils covered and uncovered with cadmium irradiated in the installation was used, analyzed by a high Pure Germanium semiconductor detector, coupled to an electronic system suitable for gamma spectrometry. The results were processed with the SAND-BP code. The doses due to gamma and neutron rays were determined using thermoluminescent dosimeters TLD 400 and TLD 700 sensitive to gamma and TLD 600, sensitive to neutrons. The TLDs were selected and used for obtaining the calibration curves - dosimeter answer versus dose - from each of the TLD three types, which were necessary to calculate the doses due to neutron and gamma, in the sample position. The radiation field, in the sample irradiation position, was characterized flux for thermal neutrons of 1.39.10 8 ± 0,12.10 8 n/cm 2 s the doses due to thermal neutrons are three times higher than those due to gamma radiation and confirm the reproducibility and consistency of the experimental findings obtained. Considering these results, the neutron field and gamma radiation showed to be appropriated for research in BNCT. (author)

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

International Nuclear Information System (INIS)

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

1993-01-01

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

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

International Nuclear Information System (INIS)

Sun, Ting; Zhang, Zizhu; Li, Bin; Chen, Guilin; Xie, Xueshun; Wei, Yongxin; Wu, Jie; Zhou, Youxin; Du, Ziwei

2013-01-01

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

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

International Nuclear Information System (INIS)

Kabalka, G. W.

2005-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Bortolussi, S., E-mail: silva.bortolussi@pv.infn.i [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bakeine, J.G. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Ballarini, F. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Gadan, M.A. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Protti, N.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Clerici, A.; Ferrari, C.; Cansolino, L.; Zonta, C.; Zonta, A. [Department of Surgery, University of Pavia, via Ferrata 27100 Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, via Ferrata 27100 Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy)

2011-02-15

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

Tandem-ESQ for accelerator-based BNCT

International Nuclear Information System (INIS)

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

2006-01-01

A project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT) is described. A folded tandem, with 1.25 MV terminal voltage, combined with an ElectroStatic Quadrupole (ESQ) chain is being proposed. The project goal is a machine capable of delivering 30 mA of 2.5 MeV protons to be used in conjunction with a neutron production target based on the 7 Li(p,n) 7 Be reaction beyond its resonance at 2.25 MeV. 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) 7 Be reaction, to perform BNCT treatment for deep-seated tumors in less than an hour. This electrostatic machine is the technologically simplest and cheapest solution for optimized AB-BNCT. (author)

Comparison and analysis of BNCT radiation dose between gold wire and JCDS measurement

International Nuclear Information System (INIS)

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

2006-01-01

We compared and evaluated boron neutron capture therapy (BNCT) radiation dose between gold wire measurement and JAERI Computational Dosimetry System (JCDS). Gold wire analysis demonstrates the actual BNCT dose though it dose not reflect the real the maximum and minimum dose in tumor tissue. We can conclude that JCDS is precise and high-reliable dose planning system for BNCT. (author)

Protocols for BNCT of glioblastoma multiforme at Brookhaven: Practical considerations

Energy Technology Data Exchange (ETDEWEB)

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

1996-12-31

In this report we discuss some issues considered in selecting initial protocols for boron neutron capture therapy (BNCT) of human glioblastoma multiforme. First the tolerance of normal tissues, especially the brain, to the radiation field. Radiation doses limits were based on results with human and animal exposures. Estimates of tumor control doses were based on the results of single-fraction photon therapy and single fraction BNCT both in humans and experimental animals. Of the two boron compounds (BSH and BPA), BPA was chosen since a FDA-sanctioned protocol for distribution in humans was in effect at the time the first BNCT protocols were written and therapy studies in experimental animals had shown it to be more effective than BSH.

Experience of boron neutron capture therapy in Japan

International Nuclear Information System (INIS)

Kanda, K.

2004-01-01

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

A clinical trial protocol for second line treatment of malignant brain tumors with BNCT at University of Tsukuba

International Nuclear Information System (INIS)

Aiyama, H.; Nakai, K.; Yamamoto, T.; Nariai, T.; Kumada, H.; Ishikawa, E.; Isobe, T.; Endo, K.; Takada, T.; Yoshida, F.; Shibata, Y.; Matsumura, A.

2011-01-01

We have evaluated the efficacy and safety of boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor using a new protocol. One of the two patients enrolled in this trial is a man with recurrent glioblastoma and the other is a woman with anaplastic meningioma. Both are still alive and no severe adverse events have been observed. Our findings suggest that NCT will be safe as a palliative therapy for malignant brain tumors. - Highlights: ► Boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor. ► Two cases with recurrent glioblastoma and anaplastic meningioma. ► No severe adverse events have been observed using BNCT. ► BNCT has a possibility of a safe palliative therapy for malignant brain tumors.

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

Science.gov (United States)

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

2017-01-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Rhodium self-powered neutron detector as a suitable on-line thermal neutron flux monitor in BNCT treatments.

Science.gov (United States)

Miller, Marcelo E; Sztejnberg, Manuel L; González, Sara J; Thorp, Silvia I; Longhino, Juan M; Estryk, Guillermo

2011-12-01

A rhodium self-powered neutron detector (Rh SPND) has been specifically developed by the Comisión Nacional de Energía Atómica (CNEA) of Argentina to measure locally and in real time thermal neutron fluxes in patients treated with boron neutron capture therapy (BNCT). In this work, the thermal and epithermal neutron response of the Rh SPND was evaluated by studying the detector response to two different reactor spectra. In addition, during clinical trials of the BNCT Project of the CNEA, on-line neutron flux measurements using the specially designed detector were assessed. The first calibration of the detector was done with the well-thermalized neutron spectrum of the CNEA RA-3 reactor thermal column. For this purpose, the reactor spectrum was approximated by a Maxwell-Boltzmann distribution in the thermal energy range. The second calibration was done at different positions along the central axis of a water-filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been well characterized by both calculation and measurement, and it presented some marked differences with the ideal spectrum considered for SPND calibrations at RA-3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom and thus the percentage of the epithermal contribution to the total neutron flux changed at each measurement location. Local (one point-position) and global (several points-positions) and thermal and mixed-field thermal neutron sensitivities were determined from these measurements. Thermal neutron flux was also measured during BNCT clinical trials within the irradiation fields incident on the patients. In order to achieve this, the detector was placed on patient's skin at dosimetric reference points for each one of the fields. System stability was adequate for this kind of measurement. Local mixed-field thermal neutron sensitivities and global thermal and mixed

Rhodium self-powered neutron detector as a suitable on-line thermal neutron flux monitor in BNCT treatments

Energy Technology Data Exchange (ETDEWEB)

Miller, Marcelo E.; Sztejnberg, Manuel L.; Gonzalez, Sara J.; Thorp, Silvia I.; Longhino, Juan M.; Estryk, Guillermo [Comision Nacional de Energia Atomica, Av. del Libertador 8250, Ciudad de Buenos Aires 1429 (Argentina); Comision Nacional de Energia Atomica, Av. del Libertador 8250, Ciudad de Buenos Aires 1429, Argentina and CONICET, Av. Rivadavia 1917, Ciudad de Buenos Aires 1033 (Argentina); Comision Nacional de Energia Atomica, Av. del Libertador 8250, Ciudad de Buenos Aires 1429 (Argentina)

2011-12-15

Purpose: A rhodium self-powered neutron detector (Rh SPND) has been specifically developed by the Comision Nacional de Energia Atomica (CNEA) of Argentina to measure locally and in real time thermal neutron fluxes in patients treated with boron neutron capture therapy (BNCT). In this work, the thermal and epithermal neutron response of the Rh SPND was evaluated by studying the detector response to two different reactor spectra. In addition, during clinical trials of the BNCT Project of the CNEA, on-line neutron flux measurements using the specially designed detector were assessed. Methods: The first calibration of the detector was done with the well-thermalized neutron spectrum of the CNEA RA-3 reactor thermal column. For this purpose, the reactor spectrum was approximated by a Maxwell-Boltzmann distribution in the thermal energy range. The second calibration was done at different positions along the central axis of a water-filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been well characterized by both calculation and measurement, and it presented some marked differences with the ideal spectrum considered for SPND calibrations at RA-3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom and thus the percentage of the epithermal contribution to the total neutron flux changed at each measurement location. Local (one point-position) and global (several points-positions) and thermal and mixed-field thermal neutron sensitivities were determined from these measurements. Thermal neutron flux was also measured during BNCT clinical trials within the irradiation fields incident on the patients. In order to achieve this, the detector was placed on patient's skin at dosimetric reference points for each one of the fields. System stability was adequate for this kind of measurement. Results: Local mixed-field thermal neutron sensitivities and

Rhodium self-powered neutron detector as a suitable on-line thermal neutron flux monitor in BNCT treatments

International Nuclear Information System (INIS)

Miller, Marcelo E.; Sztejnberg, Manuel L.; Gonzalez, Sara J.; Thorp, Silvia I.; Longhino, Juan M.; Estryk, Guillermo

2011-01-01

Purpose: A rhodium self-powered neutron detector (Rh SPND) has been specifically developed by the Comision Nacional de Energia Atomica (CNEA) of Argentina to measure locally and in real time thermal neutron fluxes in patients treated with boron neutron capture therapy (BNCT). In this work, the thermal and epithermal neutron response of the Rh SPND was evaluated by studying the detector response to two different reactor spectra. In addition, during clinical trials of the BNCT Project of the CNEA, on-line neutron flux measurements using the specially designed detector were assessed. Methods: The first calibration of the detector was done with the well-thermalized neutron spectrum of the CNEA RA-3 reactor thermal column. For this purpose, the reactor spectrum was approximated by a Maxwell-Boltzmann distribution in the thermal energy range. The second calibration was done at different positions along the central axis of a water-filled cylindrical phantom, placed in the mixed thermal-epithermal neutron beam of CNEA RA-6 reactor. In this latter case, the RA-6 neutron spectrum had been well characterized by both calculation and measurement, and it presented some marked differences with the ideal spectrum considered for SPND calibrations at RA-3. In addition, the RA-6 neutron spectrum varied with depth in the water phantom and thus the percentage of the epithermal contribution to the total neutron flux changed at each measurement location. Local (one point-position) and global (several points-positions) and thermal and mixed-field thermal neutron sensitivities were determined from these measurements. Thermal neutron flux was also measured during BNCT clinical trials within the irradiation fields incident on the patients. In order to achieve this, the detector was placed on patient's skin at dosimetric reference points for each one of the fields. System stability was adequate for this kind of measurement. Results: Local mixed-field thermal neutron sensitivities and global

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Early effects of boron neutron capture therapy on rat glioma models

International Nuclear Information System (INIS)

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

2006-01-01

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

Analysis of MCNP simulated gamma spectra of CdTe detectors for boron neutron capture therapy.

Science.gov (United States)

Winkler, Alexander; Koivunoro, Hanna; Savolainen, Sauli

2017-06-01

The next step in the boron neutron capture therapy (BNCT) is the real time imaging of the boron concentration in healthy and tumor tissue. Monte Carlo simulations are employed to predict the detector response required to realize single-photon emission computed tomography in BNCT, but have failed to correctly resemble measured data for cadmium telluride detectors. In this study we have tested the gamma production cross-section data tables of commonly used libraries in the Monte Carlo code MCNP in comparison to measurements. The cross section data table TENDL-2008-ACE is reproducing measured data best, whilst the commonly used ENDL92 and other studied libraries do not include correct tables for the gamma production from the cadmium neutron capture reaction that is occurring inside the detector. Furthermore, we have discussed the size of the annihilation peaks of spectra obtained by cadmium telluride and germanium detectors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Boron biodistribution for BNCT in the hamster cheek pouch oral cancer model: Combined administration of BSH and BPA

Energy Technology Data Exchange (ETDEWEB)

D.W. Nigg; William Bauer; Various Others

2014-06-01

Sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically for BNCT. We examined the biodistribution of BSH and BPA administered jointly in different proportions in the hamster cheek pouch oral cancer model. The 3 assayed protocols were non-toxic, and showed preferential tumor boron uptake versus precancerous and normal tissue and therapeutic tumor boron concentration values (70–85 ppm). All 3 protocols warrant assessment in BNCT studies to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology for head and neck cancer and optimize therapeutic efficacy.

Boron neutron capture therapy in cancer: past, present and future

Energy Technology Data Exchange (ETDEWEB)

Pisarev, Mario A.; Dagrosa, Maria Alejandra; Juvenal, Guilermo J. [National Atomic Energy Commission, Buenos Aires (Argentina). Div. of Nuclear Biochemistry; University of Buenos Aires (Argentina). School of Medicine. Dept. of Human Biochemistry

2007-07-15

Undifferentiated thyroid cancer (UTC) is a very aggressive tumor with no effective treatment, since it lacks iodine uptake and does not respond to radio or chemotherapy. The prognosis of these patients is bad, due to the rapid growth of the tumor and the early development of metastasis. Boron neutron capture therapy (BNCT) is based on the selective uptake of certain boron non-radioactive compounds by a tumor, and the subsequent irradiation of the area with an appropriate neutron beam. {sup 10}B is then activated to {sup 11}B, which will immediately decay releasing alpha particles and {sup 7}Li, of high linear energy transfer (LET) and limited reach. Clinical trials are being performed in patients with glioblastoma multiform and melanoma. We have explored its possible application to UTC. Our results demonstrated that a cell line of human UTC has a selective uptake of borophenylalanine (BPA) both in vitro and after transplantation to nude mice. Treatment of mice by BNCT led to a complete control of growth and cure of 100% of the animals. Moreover dogs with spontaneous UTC also have a selective uptake of BPA. At the present we are studying the biodistribution of BPA in patients with UTC before its application in humans. (author)

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.

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)

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

International Nuclear Information System (INIS)

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

2014-01-01

We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,L-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content. - Highlights: • Herein, we have synthesized boron-modified diblock copolymer. • Bpin-PLA-PEOz, which will be served as new boron containing vehicle for transporting the boron drug. • This boron containing Bpin-PLA-PEOz micelle was low toxicity can be applied to drug delivery

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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)

A clinical trial protocol for second line treatment of malignant brain tumors with BNCT at University of Tsukuba

Energy Technology Data Exchange (ETDEWEB)

Aiyama, H. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Nakai, K., E-mail: knakai@Neurosurg-tsukuba.com [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Yamamoto, T. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan)] [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Nariai, T. [Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyouku (Japan); Kumada, H. [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Ishikawa, E. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Isobe, T. [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Endo, K.; Takada, T.; Yoshida, F.; Shibata, Y.; Matsumura, A. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan)

2011-12-15

We have evaluated the efficacy and safety of boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor using a new protocol. One of the two patients enrolled in this trial is a man with recurrent glioblastoma and the other is a woman with anaplastic meningioma. Both are still alive and no severe adverse events have been observed. Our findings suggest that NCT will be safe as a palliative therapy for malignant brain tumors. - Highlights: Black-Right-Pointing-Pointer Boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor. Black-Right-Pointing-Pointer Two cases with recurrent glioblastoma and anaplastic meningioma. Black-Right-Pointing-Pointer No severe adverse events have been observed using BNCT. Black-Right-Pointing-Pointer BNCT has a possibility of a safe palliative therapy for malignant brain tumors.

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

Energy Technology Data Exchange (ETDEWEB)

Schmitz, Tobias

2016-01-22

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

The Phase I/II BNCT Trials at the Brookhaven medical research reactor: Critical considerations

International Nuclear Information System (INIS)

Diaz, A.Z.

2001-01-01

A phase I/II clinical trial of boronophenylalanine-fructose (BPA-F) mediated boron neutron capture therapy (BNCT) for Glioblastoma Multiforme (GBM) was initiated at Brookhaven National Laboratory (BNL) in 1994. Many critical issues were considered during the design of the first of many sequential dose escalation protocols. These critical issues included patient selection criteria, boron delivery agent, dose limits to the normal brain, dose escalation schemes for both neutron exposure and boron dose, and fractionation. As the clinical protocols progressed and evaluation of the tolerance of the central nervous system (CNS) to BPA-mediated BNCT at the BMRR continued new specifications were adopted. Clinical data reflecting the progression of the protocols will be presented to illustrate the steps taken and the reasons behind their adoption. (author)

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

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

Science.gov (United States)

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

2017-06-01

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

Effects of secondary interactions on the dose calculation in treatments with Boron Neutron Capture Therapy (BNCT)

International Nuclear Information System (INIS)

Monteiro, E.

2004-01-01

The aimed of this work consists of evaluating the influence of the secondary contributions of dose (thermal neutrons dose, epithermal neutrons dose, fast neutrons dose and photon dose) in treatment planning with BNCT. MCNP4B Code was used to calculate RBE-Gy doses through the irradiation of the modified Snyder head head phantom.A reduction of the therapeutical gain of monoenergetic neutron beans was observed in non invasive treatments, provoked for the predominance of the fast neutron dose component in the skin, showing that the secondary contributions of dose can contribute more in the direction to raise the dose in the fabric healthy that in the tumor, thus reducing the treatment efficiency. (author)

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

International Nuclear Information System (INIS)

Matsumoto, Tetsuo; Fukushima, Yuji

2001-01-01

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 10 8 ncm -2 s -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)

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Research needs for neutron capture therapy

International Nuclear Information System (INIS)

1995-01-01

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

Measurement and simulation of the TRR BNCT beam parameters

Energy Technology Data Exchange (ETDEWEB)

Bavarnegin, Elham [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Department of Physics, University of Guilan, Rasht (Iran, Islamic Republic of); Sadremomtaz, Alireza [Department of Physics, University of Guilan, Rasht (Iran, Islamic Republic of); Khalafi, Hossein [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Kasesaz, Yaser, E-mail: ykasesaz@aeoi.org.ir [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Golshanian, Mohadeseh; Ghods, Hossein; Ezzati, Arsalan; Keyvani, Mehdi; Haddadi, Mohammad [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of)

2016-09-11

Recently, the configuration of the Tehran Research Reactor (TRR) thermal column has been modified and a proper thermal neutron beam for preclinical Boron Neutron Capture Therapy (BNCT) has been obtained. In this study, simulations and experimental measurements have been carried out to identify the BNCT beam parameters including the beam uniformity, the distribution of the thermal neutron dose, boron dose, gamma dose in a phantom and also the Therapeutic Gain (TG). To do this, the entire TRR structure including the reactor core, pool, the thermal column and beam tubes have been modeled using MCNPX Monte Carlo code. To measure in-phantom dose distribution a special head phantom has been constructed and foil activation techniques and TLD700 dosimeter have been used. The results show that there is enough uniformity in TRR thermal BNCT beam. TG parameter has the maximum value of 5.7 at the depth of 1 cm from the surface of the phantom, confirming that TRR thermal neutron beam has potential for being used in treatment of superficial brain tumors. For the purpose of a clinical trial, more modifications need to be done at the reactor, as, for example design, and construction of a treatment room at the beam exit which is our plan for future. To date, this beam is usable for biological studies and animal trials. There is a relatively good agreement between simulation and measurement especially within a diameter of 10 cm which is the dimension of usual BNCT beam ports. This relatively good agreement enables a more precise prediction of the irradiation conditions needed for future experiments.

Might iodomethyl-α-tyrosine be a surrogate for BPA in BNCT?

International Nuclear Information System (INIS)

Miura, Michiko; Micca, P.L.; Nawrocky, M.M.; Slatkin, D.N.

1996-01-01

A single-photon emission computed tomography [SPECT] imaging agent that is an analogue of a boron carrier for boron neutron-capture therapy [BNCT] of cerebral gliomas would be useful for assessing the kinetics of boron uptake in tumors and in the surrounding brain tissues noninvasively. BNCT is based on the interaction of thermalized neutrons with 10 B nuclei in the targeted tumor. For BNCT of brain tumors, it is crucial that 10 B concentrations in radiosensitive regions of the brain be minimal since malignant cells and vital brain tissues are often inter-mingled at the margins of the tumor. Currently, boronophenylalanine [BPA]-mediated BNCT is undergoing preliminary clinical study for postoperative radiotherapy of glioblastorna multiforme at Brookhaven National Laboratory. Investigators in Japan are developing 18 F-fluoroboronophenylaianine [FBPA] as a positron 18 F (T 1/2 = 110 min), which is usually emission tomography [PET] surrogate for BPA. generated at a cyclotron dedicated to PET, is generally a minimally perturbing substitute for the 2-H on the aromatic ring because of its small size and the strong covalent bond it forms with carbon. However, SPECT has potential advantages over PET: (1) SPECT is clinically more widely available at lower cost; (2) most radioisotopes for the synthesis of SPECT agents can be purchased; (3) SPECT is less difficult to implement. It is thought that the quality of images derived from the two techniques would each be sufficiently informative for BNCT treatment planning purposes, provided that the SPECT and PET agents being considered were both pharmacokinetic surrogates for BPA. This study evaluated the use of 123 I alpha methyltyrosine as a surrogate for BPA in BNCT

Might iodomethyl-{alpha}-tyrosine be a surrogate for BPA in BNCT?

Energy Technology Data Exchange (ETDEWEB)

Miura, Michiko; Micca, P.L.; Nawrocky, M.M.; Slatkin, D.N.

1996-12-31

A single-photon emission computed tomography [SPECT] imaging agent that is an analogue of a boron carrier for boron neutron-capture therapy [BNCT] of cerebral gliomas would be useful for assessing the kinetics of boron uptake in tumors and in the surrounding brain tissues noninvasively. BNCT is based on the interaction of thermalized neutrons with {sup 10}B nuclei in the targeted tumor. For BNCT of brain tumors, it is crucial that {sup 10}B concentrations in radiosensitive regions of the brain be minimal since malignant cells and vital brain tissues are often inter-mingled at the margins of the tumor. Currently, boronophenylalanine [BPA]-mediated BNCT is undergoing preliminary clinical study for postoperative radiotherapy of glioblastorna multiforme at Brookhaven National Laboratory. Investigators in Japan are developing {sup 18}F-fluoroboronophenylaianine [FBPA] as a positron {sup 18}F (T{sub 1/2} = 110 min), which is usually emission tomography [PET] surrogate for BPA. generated at a cyclotron dedicated to PET, is generally a minimally perturbing substitute for the 2-H on the aromatic ring because of its small size and the strong covalent bond it forms with carbon. However, SPECT has potential advantages over PET: (1) SPECT is clinically more widely available at lower cost; (2) most radioisotopes for the synthesis of SPECT agents can be purchased; (3) SPECT is less difficult to implement. It is thought that the quality of images derived from the two techniques would each be sufficiently informative for BNCT treatment planning purposes, provided that the SPECT and PET agents being considered were both pharmacokinetic surrogates for BPA. This study evaluated the use of {sup 123}I alpha methyltyrosine as a surrogate for BPA in BNCT.

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

International Nuclear Information System (INIS)

Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito

2014-01-01

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

A case of astrocytoma, 19 year history after BNCT

International Nuclear Information System (INIS)

Kamano, Shuji

2006-01-01

A 39-year-old man had received Boron Neutron Capture Therapy (BNCT) in 1987 for a Grade II Astrocytoma. He gradually exacerbated and received a second operation in 1994. The mass taken in the second operation is almost competent with radiation necrosis. Following that, he shows no signs of recurrence. Currently, he has returned to full time employment in physical labor. This case suggests effectiveness of BNCT for rather low-grade astrocytomas. (author)

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

Science.gov (United States)

Halfon, S; Arenshtam, A; Kijel, D; Paul, M; Weissman, L; Berkovits, D; Eliyahu, I; Feinberg, G; Kreisel, A; Mardor, I; Shimel, G; Shor, A; Silverman, I; Tessler, M

2015-12-01

A free surface liquid-lithium jet target is operating routinely at Soreq Applied Research Accelerator Facility (SARAF), bombarded with a ~1.91 MeV, ~1.2 mA continuous-wave narrow proton beam. The experiments demonstrate the liquid lithium target (LiLiT) capability to constitute an intense source of epithermal neutrons, for Accelerator based Boron Neutron Capture Therapy (BNCT). The target dissipates extremely high ion beam power densities (>3 kW/cm(2), >0.5 MW/cm(3)) for long periods of time, while maintaining stable conditions and localized residual activity. LiLiT generates ~3×10(10) n/s, which is more than one order of magnitude larger than conventional (7)Li(p,n)-based near threshold neutron sources. A shield and moderator assembly for BNCT, with LiLiT irradiated with protons at 1.91 MeV, was designed based on Monte Carlo (MCNP) simulations of BNCT-doses produced in a phantom. According to these simulations it was found that a ~15 mA near threshold proton current will apply the therapeutic doses in ~1h treatment duration. According to our present results, such high current beams can be dissipated in a liquid-lithium target, hence the target design is readily applicable for accelerator-based BNCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

A Tandem-electrostatic-quadrupole for accelerator-based BNCT

International Nuclear Information System (INIS)

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

2007-01-01

A project to develop a Tandem-electrostatic-quadrupole (TESQ) accelerator for accelerator-based boron neutron capture therapy (AB-BNCT) is described. A folded Tandem, with 1.25 MV terminal voltage, combined with an electrostatic quadrupole (ESQ) chain is being proposed. The project goal is a machine capable of delivering 30 mA of 2.5 MeV protons to be used in conjunction with a neutron production target based on the 7 Li(p, n) 7 Be reaction slightly beyond its resonance at 2.25 MeV. 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 7 Li(p, n) 7 Be reaction, to perform BNCT treatment for deep-seated tumors in less than an hour. This electrostatic machine is the technologically simplest and cheapest solution for optimized AB-BNCT

Characterisation of the TAPIRO BNCT epithermal facility

Energy Technology Data Exchange (ETDEWEB)

Burn, K. W. [FIS-NUC, ENEA, Via Martiri di Montesole 4, Bologna (Italy); Colli, V. [Dept. of Physics of Univ., INFN, Via Celoria 16, I-20133 Milano (Italy); Curzio, G.; D' Errico, F. [DIMNP, Univ. of Pisa, Via Diotisalvi 2, I-56126 Pisa (Italy); Gambarini, G. [Dept. of Physics of Univ., INFN, Via Celoria 16, I-20133 Milano (Italy); Rosi, G. [FIS-ION, ENEA, Casaccia, Via Anguillarese 301, I-00060 Santa Maria di Galeria, Roma (Italy); Scolari, L. [Dept. of Physics of Univ., INFN, Via Celoria 16, I-20133 Milano (Italy)

2004-07-01

A collimated epithermal beam for boron neutron capture therapy (BNCT) research has been designed and built at the TAPIRO fast research reactor. A complete experimental characterisation of the radiation field in the irradiation chamber has been performed, to verify agreement with IAEA requirements. Slow neutron fluxes have been measured by means of an activation technique and with thermoluminescent detectors (TLDs). The fast neutron dose has been determined with gel dosemeters, while the fast neutron spectrum has been acquired by means of a neutron spectrometer based on superheated drop detectors. The gamma-dose has been measured with gel dosemeters and TLDs. For an independent verification of the experimental results, fluxes, doses and neutron spectra have been calculated with Monte Carlo simulations using the codes MCNP4B and MCNPX 2.1.5 with the direct statistical approach (DSA). The results obtained confirm that the epithermal beams achievable at TAPIRO are of suitable quality for BNCT purposes. (authors)

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

International Nuclear Information System (INIS)

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

1994-01-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

Monte Carlo simulations were performed to evaluate dose for possible treatment of cancers by boron neutron capture therapy (BNCT). The computational model of male Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the lung. Calculations have been performed by means of the MCNP5/X code. In this simulation, two opposite neutron beams were considered, in order to obtain uniform neutron flux distribution inside the lung. The obtained results indicate that the lung cancer could be treated by BNCT under the assumptions of calculations. The difference in evaluated dose in cancer and normal lung tissue suggests that BNCT could be applied for the treatment of cancers. The difference in exposure of cancer and healthy tissue can be observed, so the healthy tissue can be spared from damage. An absorbed dose ratio of metastatic tissue-to-the healthy tissue was ∼5. Absorbed dose to all other organs was low when compared with the lung dose. Absorbed dose depth distribution shows that BNC therapy can be very useful in the treatments for tumour. The ratio of the tumour absorbed dose and irradiated healthy tissue absorbed dose was also ∼5. It was seen that an elliptical neutron field was better irradiation choice. (authors)

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Design of a boron neutron capture enhanced fast neutron therapy assembly

Energy Technology Data Exchange (ETDEWEB)

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

2006-12-01

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

Design study of a medical reactor for Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Sasaki, M.; Hirota, J.; Tamao, S.; Kanda, K.; Mishima, Y.

1992-01-01

A new design study of a medical reactor for Boron Neutron Capture Therapy (BNCT) has been carried out. The reactor is to be used exclusively for the treatment of malignant melanoma and other cancers as well as for the further biomedical research. Main specifications of the reactor are as follows; thermal power of 2 MW, water cooling by natural convection, semitight core of triangular lattice, UO 2 fuel rod of 9.5 mm diameter and no refueling in the reactor-life. Three horizontal and one vertical neutron beam hole are to be provided to deliver thermal and epithermal neutrons. N-γ coupling Sn transport calculations indicate that the patient treatment period will be about 30 minutes with minimal fast neutron and gamma contaminants. (author)

TU-FG-BRB-07: GPU-Based Prompt Gamma Ray Imaging From Boron Neutron Capture Therapy

Energy Technology Data Exchange (ETDEWEB)

Kim, S; Suh, T; Yoon, D; Jung, J; Shin, H; Kim, M [The catholic university of Korea, Seoul (Korea, Republic of)

2016-06-15

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). Conclusion: 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 reconstruction using the GPU computation for BNCT simulations.

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...

Carborane-containing metalloporphyrins for BNCT

International Nuclear Information System (INIS)

Miura, Michiko; Joel, D.D.; Nawrocky, M.M.; Micca, P.L.

1996-01-01

For BNCT of malignant brain tumors, it is crucial that there be relatively high boron concentrations in tumor compared with normal tissues within the neutron-irradiated treatment volume. Fairchild and Bond estimated that major advances in BNCT should be possible if ratios of 10 B concentrations in tumor to those in normal tissue (e.g. brain and blood) were at least 5: 1. Given that the only current boron carrier being tested clinically in the U.S., p-boronophenyl-alanine[BPA], yields tumor blood and tumor brain ratios of about 3:1, the criteria for new boronated compounds should be to at least match these ratios and maintain tumor boron concentrations greater than 30 μg B/g. Although previously tested boronated porphyrins have not only matched but surpassed these ratios, it was at a cost of greater toxicity. Chemical and hematological assays of blood analytes; showed marked thrombocytopenia, a decrease to about one-tenth the normal concentration of platelets circulating in the blood, in addition to abnormalities in concentrations of circulating enzymes, that indicated liver toxicity. The physical appearance and behavior of the affected mice were different from those of mice injected with solvent only. Although thrombocytopenia and other toxic effects had disappeared after a few days, previously tested porphyrins would not be safe to infuse into patients for BNCT of potentially hemorrhagic malignant tumors in the brain such as glioblastoma multiforme and metastatic melanoma. We synthesized a different boronated porphyrin, tetracarboranylphenylporphyrin, [TCP] and inserted nickel, copper, or manganese into its coordination center. Biological studies of NiTCP in mice and of CuTCP in rats show that these compounds elicit little or no toxicity when given at potentially therapeutic doses

Carborane-containing metalloporphyrins for BNCT

Energy Technology Data Exchange (ETDEWEB)

Miura, Michiko; Joel, D.D.; Nawrocky, M.M.; Micca, P.L. [and others

1996-12-31

For BNCT of malignant brain tumors, it is crucial that there be relatively high boron concentrations in tumor compared with normal tissues within the neutron-irradiated treatment volume. Fairchild and Bond estimated that major advances in BNCT should be possible if ratios of {sup 10}B concentrations in tumor to those in normal tissue (e.g. brain and blood) were at least 5: 1. Given that the only current boron carrier being tested clinically in the U.S., p-boronophenyl-alanine[BPA], yields tumor blood and tumor brain ratios of about 3:1, the criteria for new boronated compounds should be to at least match these ratios and maintain tumor boron concentrations greater than 30 {mu}g B/g. Although previously tested boronated porphyrins have not only matched but surpassed these ratios, it was at a cost of greater toxicity. Chemical and hematological assays of blood analytes; showed marked thrombocytopenia, a decrease to about one-tenth the normal concentration of platelets circulating in the blood, in addition to abnormalities in concentrations of circulating enzymes, that indicated liver toxicity. The physical appearance and behavior of the affected mice were different from those of mice injected with solvent only. Although thrombocytopenia and other toxic effects had disappeared after a few days, previously tested porphyrins would not be safe to infuse into patients for BNCT of potentially hemorrhagic malignant tumors in the brain such as glioblastoma multiforme and metastatic melanoma. We synthesized a different boronated porphyrin, tetracarboranylphenylporphyrin, [TCP] and inserted nickel, copper, or manganese into its coordination center. Biological studies of NiTCP in mice and of CuTCP in rats show that these compounds elicit little or no toxicity when given at potentially therapeutic doses.

Nuclear engineering aspects of glioma BNCT research in Italy

International Nuclear Information System (INIS)

Curzio, G.; Mazzini, M.

1998-01-01

A research project on Boron Neutron Capture Therapy (BNCZ) of gliomas has been set up in Italy, with the participation of Departments of Oncology and Mechanical and Nuclear Construction (DCMN) of the University of Pisa, as well as the Neuroscience and Physics Departments of the Universities of Roma. The specific objective of DCMN Research Unit is the study of the physical-engineering aspects related to BNCT. The paper outlines the research lines in progress at DCMN: Monte Carlo calculations of neutron dose distribution for BNCT treatment planning; measurements of neutron fluxes, spectra and doses by neutron detectors specifically set up; design of modifications to the nuclear reactors of ENEA Casaccia Center. In particular, the paper emphasizes the most original contributions on dosimetric aspects, both from informatic and experimental points of view.(author)

Medical setup of intraoperative BNCT at JRR-4

International Nuclear Information System (INIS)

Akutsu, H.; Yamamoto, T.; Matsumura, A.

2000-01-01

Since October 1999, we have been performing clinical trials of intraoperative boron neutron capture therapy (IOBNCT) using a mixed thermal-epithermal beam at the Japan Research Reactor No. 4 (JRR-4). For immediate pre-BNCT care, including administration of a boron compound as well as post-BNCT care, a collaborating neurosurgical department of the University of Tsukuba was prepared in the vicinity of JRR-4. Following craniotomy in the treatment room, anesthetized patients were transported into the irradiation room for BNCT. The boron concentration in tissue was measured by the PGA and ICP-AES methods. The long-term follow-up was done at the University of Tsukuba Hospital. IOBNCT is a complex clinical procedure, which requires sophisticated operating team and co-medical staffs and also cooperation with physicist team. IOBNCT is a complex clinical procedure requiring a high level of cooperation among the operating team, co-medical staff, and physicists. For the safe and successful performance of IOBNCT, we have made the program including critical pathway and prepared various equipments for IOBNCT. To ensure the safe and successful performance of IOBNCT, we developed a critical pathway for use during the procedure, and prepared various apparatus for IOBNCT. (author)

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

International Nuclear Information System (INIS)

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

2012-01-01

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

PET pharmacokinetic analysis to estimate boron concentration in tumor and brain as a guide to plan BNCT for malignant cerebral glioma

International Nuclear Information System (INIS)

Nariai, Tadashi; Ishiwata, Kiichi; Kimura, Yuichi; Inaji, Motoki; Momose, Toshiya; Yamamoto, Tetsuya; Matsumura, Akira; Ishii, Kenji; Ohno, Kikuo

2009-01-01

Introduction: To plan the optimal BNCT for patients with malignant cerebral glioma, estimation of the ratio of boron concentration in tumor tissue against that in the surrounding normal brain (T/N ratio of boron) is important. We report a positron emission tomography (PET) imaging method to estimate T/N ratio of tissue boron concentration based on pharmacokinetic analysis of amino acid probes. Methods: Twelve patients with cerebral malignant glioma underwent 60 min dynamic PET scanning of brain after bolus injection of 18 F-borono-phenyl-alanine (FBPA) with timed arterial blood sampling. Using kinetic parameter obtained by this scan, T/N ratio of boron concentration elicited by one-hour constant infusion of BPA, as performed in BNCT, was simulated on Runge-Kutta algorithm. 11 C-methionine (MET) PET scan, which is commonly used in worldwide PET center as brain tumor imaging tool, was also performed on the same day to compare the image characteristics of FBPA and that of MET. Result: PET glioma images obtained with FBPA and MET are almost identical in all patients by visual inspection. Estimated T/N ratio of tissue boron concentration after one-hour constant infusion of BPA, T/N ratio of FBPA on static condition, and T/N ratio of MET on static condition showed significant linear correlation between each other. Conclusion: T/N ratio of boron concentration that is obtained by constant infusion of BPA during BNCT can be estimated by FBPA PET scan. This ratio can also be estimated by MET-PET imaging. As MET-PET study is available in many clinical PET center, selection of candidates for BNCT may be possible by MET-PET images. Accurate planning of BNCT may be performed by static images of FBPA PET. Use of PET imaging with amino acid probes may contribute very much to establish an appropriate application of BNCT for patients with malignant glioma.

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.

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

INEL BNCT research program: Annual report, 1995

Energy Technology Data Exchange (ETDEWEB)

Venhuizen, J.R. [ed.

1996-04-01

This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1995. Contributions from the principal investigators about their individual projects are included, specifically, physics (treatment planning software, real-time neutron beam measurement dosimetry), and radiation biology (large animal models efficacy studies). Design of a reactor based epithermal neutron extraction facility is discussed in detail. Final results of boron magnetic resonance imagining is included for both borocaptate sodium (BSH) and boronophenylalanine (BPA) in rats, and BSH in humans. Design of an epithermal neutron facility using electron linear accelerators is presented, including a treatise on energy removal from the beam target. Information on the multiple fraction injection of BSH in rats is presented.

INEL BNCT research program: Annual report, 1995

International Nuclear Information System (INIS)

Venhuizen, J.R.

1996-04-01

This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1995. Contributions from the principal investigators about their individual projects are included, specifically, physics (treatment planning software, real-time neutron beam measurement dosimetry), and radiation biology (large animal models efficacy studies). Design of a reactor based epithermal neutron extraction facility is discussed in detail. Final results of boron magnetic resonance imagining is included for both borocaptate sodium (BSH) and boronophenylalanine (BPA) in rats, and BSH in humans. Design of an epithermal neutron facility using electron linear accelerators is presented, including a treatise on energy removal from the beam target. Information on the multiple fraction injection of BSH in rats is presented

Radiation transport calculation methods in BNCT

International Nuclear Information System (INIS)

Koivunoro, H.; Seppaelae, T.; Savolainen, S.

2000-01-01

Boron neutron capture therapy (BNCT) is used as a radiotherapy for malignant brain tumours. Radiation dose distribution is necessary to determine individually for each patient. Radiation transport and dose distribution calculations in BNCT are more complicated than in conventional radiotherapy. Total dose in BNCT consists of several different dose components. The most important dose component for tumour control is therapeutic boron dose D B . The other dose components are gamma dose D g , incident fast neutron dose D f ast n and nitrogen dose D N . Total dose is a weighted sum of the dose components. Calculation of neutron and photon flux is a complex problem and requires numerical methods, i.e. deterministic or stochastic simulation methods. Deterministic methods are based on the numerical solution of Boltzmann transport equation. Such are discrete ordinates (SN) and spherical harmonics (PN) methods. The stochastic simulation method for calculation of radiation transport is known as Monte Carlo method. In the deterministic methods the spatial geometry is partitioned into mesh elements. In SN method angular integrals of the transport equation are replaced with weighted sums over a set of discrete angular directions. Flux is calculated iteratively for all these mesh elements and for each discrete direction. Discrete ordinates transport codes used in the dosimetric calculations are ANISN, DORT and TORT. In PN method a Legendre expansion for angular flux is used instead of discrete direction fluxes, land the angular dependency comes a property of vector function space itself. Thus, only spatial iterations are required for resulting equations. A novel radiation transport code based on PN method and tree-multigrid technique (TMG) has been developed at VTT (Technical Research Centre of Finland). Monte Carlo method solves the radiation transport by randomly selecting neutrons and photons from a prespecified boundary source and following the histories of selected particles

Development of an anthropomorfic simulator for simulation and measurements of neutron dose and flux the facility for BNCT studies

International Nuclear Information System (INIS)

Muniz, Rafael Oliveira Rondon

2010-01-01

IPEN facility for researches in BNCT (Boron Neutron Capture Therapy) uses IEA-R1 reactor's irradiation channel number 3, where there is a mixed radiation field - neutrons and gamma. The researches in progress require the radiation fields, in the position of the irradiation of sample, to have in its composition maximized thermal neutrons component and minimized, fast and epithermal neutron flux and gamma radiation. This work was developed with the objective of evaluating whether the present radiation field in the facility is suitable for BNCT researches. In order to achieve this objective, a methodology for the dosimetry of thermal neutrons and gamma radiation in mixed fields of high doses, which was not available in IPEN, was implemented in the Center of Nuclear Engineering of IPEN, by using thermoluminescent dosimeters - TLDs 400, 600 and 700. For the measurements of thermal and epithermal neutron flux, activation detectors of gold were used applying the cadmium ratio technique. A cylindrical phantom composed by acrylic discs was developed and tested in the facility and the DOT 3.5. computational code was used in order to obtain theoretical values of neutron flux and the dose along phantom. In the position corresponding to about half the length of the cylinder of the phantom, the following values were obtained: thermal neutron flux (2,52 ± 0,06).10 8 n/cm 2 s, epithermal neutron flux (6,17 ± 0,26).10 7 .10 6 n/cm 2 s, absorbed dose due to thermal neutrons (4,2 ± 1,8)Gy and (10,1 ± 1,3)Gy due to gamma radiation. The obtained values show that the fluxes of thermal and epithermal neutrons flux are appropriate for studies in BNCT, however, the dose due to gamma radiation is high, indicating that the facility should be improved. (author)

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

International Nuclear Information System (INIS)

Irhas; Andang Widi Harto; Yohannes Sardjono

2014-01-01

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

Alpha-amino alcohol of para-boronophenylalanine, BPAol, as a potential boron carrier for BNCT

International Nuclear Information System (INIS)

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

2000-01-01

α amino alcohol of boronophenylalanine BPAol in which -COOH group is replaced with hydrophilic group of -OH of p-boronophenylalanine (BPA) has been synthesized and its BNCT effect on experimental tumor models have been investigated. Tumor cell killing effect of BPAol on C6 gliosarcoma cells was very high 4.4 times as that of BPA, since it was actively accumulated into tumor cells in 4-5 times as that of BPA. Carboxylic group of BPA might not play as an essential role in uptake of BPA into tumor cells. BPAol-based BNCT strongly inhibited the tumor growth of Green's melanotic melanoma hamsters even under therapeutic dose of BPA-based BNCT. These preliminary findings strongly warrant further extensive pre-clinical study for BPAol as a boron carrier for BNCT. (author)

Collimator and shielding design for boron neutron capture therapy (BNCT) facility at TRIGA MARK II reactor

International Nuclear Information System (INIS)

Mohd Rafi Mohd Solleh; Abdul Aziz Tajuddin; Abdul Aziz Mohamed; Eid Mahmoud Eid Abdel Munem; Mohamad Hairie Rabir; Julia Abdul Karim; Yoshiaki, Kiyanagi

2011-01-01

The geometry of reactor core, thermal column, collimator and shielding system for BNCT application of TRIGA MARK II Reactor were simulated with MCNP5 code. Neutron particle lethargy and dose were calculated with MCNPX code. Neutron flux in a sample located at the end of collimator after normalized to measured value (Eid Mahmoud Eid Abdel Munem, 2007) at 1 MW power was 1.06 x 10 8 n/ cm 2 / s. According to IAEA (2001) flux of 1.00 x 10 9 n/ cm 2 / s requires three hours of treatment. Few modifications were needed to get higher flux. (Author)

INEL BNCT Program: Volume 5, No. 9

Energy Technology Data Exchange (ETDEWEB)

Ackermann, A.L. (ed.)

1991-01-01

This Bulletin presents a summary of accomplishments and highlights of the Idaho National Engineering Laboratory's (INEL) Boron Neutron Capture Therapy (BNCT) Program for September 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, and updates to the animal data charts.

Monte Carlo simulations of the cellular S-value, lineal energy and RBE for BNCT

International Nuclear Information System (INIS)

Liu Chingsheng; Tung Chuanjong

2006-01-01

Due to the non-uniform uptake of boron-containing pharmaceuticals in cells and the short-ranged alpha and lithium particles, microdosimetry provides useful information on the cellular dose and response of boron neutron capture therapy (BNCT). Radiation dose and quality in BNCT may be expressed in terms of the cellular S-value and the lineal energy spectrum. In the present work, Monte Carlo simulations were performed to calculate these microdosimetric parameters for different source-target configurations and sizes in cells. The effective relative biological effectiveness (RBE) of the Tsing Hua Open-pool Reactor (THOR) epithermal neutron beam was evaluated using biological weighting functions that depended on the lineal energy. RBE changes with source-target configurations and sizes were analyzed. (author)

Desain Beam Shaping Assembly (BSA berbasis D-D Neutron Generator 2,45 MeV untuk Uji Fasilitas BNCT

Directory of Open Access Journals (Sweden)

Desman P. Gulo

2015-12-01

Full Text Available Boron Neutron Capture Therapy (BNCT is one of the cancer treatments that are being developed in nowadays. In order to support BNCT treatment for cancer that exists in underneath skin like breast cancer, the facility needs a generator that is able to produce epithermal neutron. One of the generator that is able to produce neutron is D-D neutron generator with 2.45 MeV energy. Based on the calculation of this paper, we found that the total production of neutron per second (neutron yield from Neutron Generator (NG by PSTA-BATAN Yogyakarta is 2.55×1011 n/s. The energy and flux that we found is in the range of quick neutron. Thus, it needs to be moderated to the level of epithermal neutron which is located in the interval energy of 1 eV to 10 KeV with 109 n/cm2s flux. This number is the recommendation standard from IAEA. Beam Shaping Assembly (BSA is needed in order to moderate the quick neutron to the level of epithermal neutron. One part of BSA that has the responsibility in moderating the quick neutron to epithermal neutron is the moderator. The substance of moderator used in this paper is MgF2 and A1F3. The thickness of moderator has been set in in such a way by using MCNPX software in order to fulfill the standard of IAEA. As the result of optimizing BSA moderator, the data obtain epithermal flux with the total number of 4.64×108 n/cm2/s for both of moderators with the thickness of moderator up to 15 cm. At the end of this research, the number of epithermal flux does not follow the standard of IAEA. This is because the flux neutron that is being produced by NG is relatively small. In conclusion, the NG from PSTA-BATAN Yogyakarta is not ready to be used for the BNCT treatment facility for the underneath skin cancer like breast cancer.

Radioprotective agents to reduce BNCT (Boron Neutron Capture Therapy) induced mucositis in the hamster cheek pouch; Agentes radioprotectores para reducir la mucositis inducida por la terapia por captura neutrónica en boro (BNCT) en la bolsa de la mejilla del hámster

Energy Technology Data Exchange (ETDEWEB)

Monti Hughes, A. [Dpto. de Radiobiología, Gerencia de Química Nuclear y Ciencias de la Salud, GAATEN, Comisión Nacional de Energía Atómica (CNEA) (Argentina); Pozzi, E. C.C. [Gerencia de Reactores de Investigación y Producción, GAATEN, CNEA (Argentina); Thorp, S., E-mail: andrea.monti@cnea.gov.ar [Sub-Gerencia Instrumentación y Control, GAEN, CNEA(Argentina)

2013-07-01

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

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

International Nuclear Information System (INIS)

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

1990-01-01

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

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.

Depth-dose evaluation for lung and pancreas cancer treatment by BNCT using an epithermal neutron beam

International Nuclear Information System (INIS)

Matsumoto, Tetsuo; Fukushima, Yuji

2000-01-01

The depth-dose distributions were evaluated for possible treatment of both lung and pancreas cancers using an epithermal neutron beam. The 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 5x10 8 ncm -2 s -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 could be applied for both lung and pancreas cancer treatment. (author)

Liquid Li based neutron source for BNCT and science application

International Nuclear Information System (INIS)

Horiike, H.; Murata, I.; Iida, T.; Yoshihashi, S.; Hoashi, E.; Kato, I.; Hashimoto, N.; Kuri, S.; Oshiro, S.

2015-01-01

Liquid lithium (Li) is a candidate material for a target of intense neutron source, heat transfer medium in space engines and charges stripper. For a medical application of BNCT, epithermal neutrons with least energetic neutrons and γ-ray are required so as to avoid unnecessary doses to a patient. This is enabled by lithium target irradiated by protons at 2.5 MeV range, with utilizing the threshold reaction of "7Li(p,n)"7Be at 1.88 MeV. In the system, protons at 2.5 MeV penetrate into Li layer by 0.25 mm with dissipating heat load near the surface. To handle it, thin film flow of high velocity is important for stable operation. For the proton accelerator, electrostatic type of the Schnkel or the tandem is planned to be employed. Neutrons generated at 0.6 MeV are gently moderated to epithermal energy while suppressing accompanying γ-ray minimum by the dedicated moderator assembly. - Highlights: • Liquid lithium (Li) is a candidate material for a target of intense neutron source. • An accelerator based neutron source with p-liquid Li target for boron neutron capture therapy is under development in Osaka University, Japan. • In our system, the harmful radiation dose due to rays and fast neutrons will be suppressed very low. • The system performance are very promising as a state of art cancer treatment system. • The project is planned as a joint undertaking between industries and Osaka University.

Adjustment methodology for preliminary study on the distribution of bone tissue boron. Potential therapeutic applications

International Nuclear Information System (INIS)

Brandizzi, D; Dagrosa, A; Carpano, M.; Olivera, M. S.; Nievas, S; Cabrini, R.L.

2013-01-01

Boron is an element that has an affinity for bone tissue and represents a considered element in bone health . Other boron compounds are used in the Boron Neutron Capture Therapy (BNCT ) in the form of sodium borocaptate (BSH ) and borono phenylalanine (BPA). The results of clinical trials up to date are encouraging but not conclusive . At an experimental level , some groups have applied BNCT in osteosarcomas . We present preliminary methodological adjustments for the presence of boron in bone. (author)

PET pharmacokinetic analysis to estimate boron concentration in tumor and brain as a guide to plan BNCT for malignant cerebral glioma

Energy Technology Data Exchange (ETDEWEB)

Nariai, Tadashi [Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo (Japan)], E-mail: nariai.nsrg@tmd.ac.jp; Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Nakacho, Itabashi-ku, Tokyo (Japan); Kimura, Yuichi [Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba (Japan); Inaji, Motoki; Momose, Toshiya [Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo (Japan); Yamamoto, Tetsuya; Matsumura, Akira [Department of Neurosurgery, University of Tsukuba, Tennodai, Tsukuba, Igaraki (Japan); Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Nakacho, Itabashi-ku, Tokyo (Japan); Ohno, Kikuo [Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo (Japan)

2009-07-15

Introduction: To plan the optimal BNCT for patients with malignant cerebral glioma, estimation of the ratio of boron concentration in tumor tissue against that in the surrounding normal brain (T/N ratio of boron) is important. We report a positron emission tomography (PET) imaging method to estimate T/N ratio of tissue boron concentration based on pharmacokinetic analysis of amino acid probes. Methods: Twelve patients with cerebral malignant glioma underwent 60 min dynamic PET scanning of brain after bolus injection of {sup 18}F-borono-phenyl-alanine (FBPA) with timed arterial blood sampling. Using kinetic parameter obtained by this scan, T/N ratio of boron concentration elicited by one-hour constant infusion of BPA, as performed in BNCT, was simulated on Runge-Kutta algorithm. {sup 11}C-methionine (MET) PET scan, which is commonly used in worldwide PET center as brain tumor imaging tool, was also performed on the same day to compare the image characteristics of FBPA and that of MET. Result: PET glioma images obtained with FBPA and MET are almost identical in all patients by visual inspection. Estimated T/N ratio of tissue boron concentration after one-hour constant infusion of BPA, T/N ratio of FBPA on static condition, and T/N ratio of MET on static condition showed significant linear correlation between each other. Conclusion: T/N ratio of boron concentration that is obtained by constant infusion of BPA during BNCT can be estimated by FBPA PET scan. This ratio can also be estimated by MET-PET imaging. As MET-PET study is available in many clinical PET center, selection of candidates for BNCT may be possible by MET-PET images. Accurate planning of BNCT may be performed by static images of FBPA PET. Use of PET imaging with amino acid probes may contribute very much to establish an appropriate application of BNCT for patients with malignant glioma.

In vivo BNCT in experimental and spontaneous tumors at RA-1 reactor

International Nuclear Information System (INIS)

Trivillin, Veronica A.; Heber, Elisa M.; Itoiz, Maria E.; Schwint, Amanda E.; Nigg, David W.

2003-01-01

Within the search for new applications of Boron Neutron Capture Therapy (BNCT) and the basic research oriented towards the study of BNCT radiobiology to optimize its therapeutic gain, we previously proposed and validated the hamster cheek pouch oral cancer model and showed, for the first time, the success of BNCT to treat oral cancer in an experimental model. The staff of the Ra-1 Reactor (Constituyentes Atomic Center) adapted the thermal beam and physical set-up to perform in vivo BNCT of superficial tumors in small animals. We preformed a preliminary characterization of the thermal beam, performed beam only irradiation of normal and tumor bearing hamsters and in vivo BNCT of experimental oral squamous cell carcinomas in hamsters mediated by boron phenylalanine (BPA) and GB-10 (Na 2 10 B 10 H 10 ). Having demonstrated the absence of radio toxic effects in healthy tissue and a therapeutic effect of in vivo BNCT in hamster cheek pouch tumors employing the Ra-1 thermal beam, we performed a feasibility study of the treatment by BNCT of 3 terminal cases of spontaneous head and neck squamous cell carcinoma in cats following the corresponding biodistribution studies. This was the first treatment of spontaneous tumors by BNCT in our country and the first treatment by BNCT in cats worldwide. This preclinical study in terminal cases showed significant tumor control by BNCT with no damage to normal tissue. (author)

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies.

Science.gov (United States)

Fujimoto, T; Andoh, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Sonobe, H; Epstein, Alan L; Akisue, T; Kirihata, M; Kurosaka, M; Fukumori, Y; Ichikawa, H

2011-12-01

Clear cell sarcoma (CCS), a rare malignant tumor with a predilection for young adults, is of poor prognosis. Recently however, boron neutron capture therapy (BNCT) with the use of p-borono-L-phenylalanine (BPA) for malignant melanoma has provided good results. CCS also produces melanin; therefore, the uptake of BPA is the key to the application of BNCT to CCS. We describe, for the first time, the high accumulation of boron in CCS and the CCS tumor-bearing animal model generated for BNCT studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Design of a BNCT facility at HANARO

International Nuclear Information System (INIS)

Jun, Byung Jin; Lee, Byung Chul

1998-01-01

Based on the feasibility study of the BNCT at HANARO, it was confirmed that only thermal BNCT is possible at the IR beam tube if appropriate filtering system be installed. Medical doctors in Korea Cancer Center Hospital agreed that the thermal BNCT facility would be worthwhile for the BNCT technology development in Korea as well as superficial cancer treatment. For the thermal BNCT to be effective, the thermal neutron flux should be high enough for patient treatment during relatively short time and also the fast neutron and gamma-ray fluxes should be as low as possible. In this point of view, the following design requirements are set up: 1) thermal neutron flux at the irradiation position should be higher than 3x10 9 n/cm 2 -sec, 2) ratio of the fast neutrons and gamma-rays to the thermal neutrons should be minimized, and 3) patient treatment should be possible without interrupt to the reactor operation. To minimize the fast neutrons and gamma-rays with the required thermal neutrons at the irradiation position, a radiation filter consisting of single crystals of silicon and bismuth at liquid nitrogen temperature is designed. For the shielding purpose around the irradiation position, polyethylene, lead, LiF, etc., are appropriately arranged around the radiation filter. A water shutter in front of the radiation filter is adopted so as to avoid interrupt to the reactor operation. At present, detail design of the radiation filter is ongoing. Cooling capabilities of the filter will be tested through a mockup experiment. Dose rate distributions around the radiation filter and a prompt gamma-ray activation analysis system for the analyses of boron content in the biological samples are under design. The construction of this facility will be started from next year if it is permitted from the regulatory body this year. Some other future works exist and are described in the paper. (author)

Optimization of the irradiation beam in the BNCT research facility at IEA-R1 reactor

International Nuclear Information System (INIS)

Castro, Vinicius Alexandre de

2014-01-01

Boron Neutron Capture Therapy (BNCT) is a radiotherapeutic technique for the treatment of some types of cancer whose useful energy comes from a nuclear reaction that occurs when thermal neutron impinges upon a Boron-10 atom. In Brazil there is a research facility built along the beam hole number 3 of the IEA-R1 research reactor at IPEN, which was designed to perform BNCT research experiments. For a good performance of the technique, the irradiation beam should be mostly composed of thermal neutrons with a minimum as possible gamma and above thermal neutron components. This work aims to monitor and evaluate the irradiation beam on the sample irradiation position through the use of activation detectors (activation foils) and also to propose, through simulation using the radiation transport code, MCNP, new sets of moderators and filters which shall deliver better irradiation fields at the irradiation sample position In this work, a simulation methodology, based on a MCNP card, known as wwg (weight window generation) was studied, and the neutron energy spectrum has been experimentally discriminated at 5 energy ranges by using a new set o activation foils. It also has been concluded that the BNCT research facility has the required thermal neutron flux to perform studies in the area and it has a great potential for improvement for tailoring the irradiation field. (author)

Towards a new therapy protocol for liver metastases. Effect of boron compounds and BNCT on normal liver regeneration

International Nuclear Information System (INIS)

Cardoso, Jorge E.; Heber, Elisa M.; Trivillin, Veronica A.

2006-01-01

The Taormina project developed a new method for BNCT treatment of multifocal unresectable liver metastases based on whole liver autograft. The Roffo Institute liver surgeons propose a new technique based on partial liver autograft that would pose less risk to the patient but would require significant healthy liver regeneration following BNCT. The aim of the present study was to assess the effect of BPA, GB-10 (Na 2 10 B 10 H 10 ) and (GB-10 + BPA) and of BNCT mediated by these boron compounds on normal liver regeneration in the Wistar rat. Normal liver regeneration, body weight, hemogram, liver and kidney function were assessed following partial hepatectomy post administration of BPA, GB-10 or (GB-10 + BPA) and post in vivo BNCT at the RA-6 Reactor. These end-points were evaluated 9 days following partial hepatectomy, the time at which complete liver regeneration occurs in untreated controls. The corresponding biodistribution studies were conducted to perform dosimetric calculations. BPA, GB-10 and (GB-10 + PBA) and in vivo BNCT mediated by these boron compounds in dose ranges compatible with therapy did not cause alterations in the outcome of normal liver regeneration, and did not induce alterations in body weight, hemogram, liver or kidney function. The experimental data available to date support the development of a new BNCT protocol for the treatment of liver metastases that requires the regeneration of normal liver past-BNCT. (author)

Dose distribution and clinical response of glioblastoma treated with boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Matsuda, M. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan)], E-mail: mhide-m@gk9.so-net.ne.jp; Yamamoto, T. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan); Kumada, H. [Japan Atomic Energy Agency, Shirakatashirane 2-4, Tokai (Japan); Nakai, K.; Shirakawa, M.; Tsurubuchi, T.; Matsumura, A. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan)

2009-07-15

The dose distribution and failure pattern after treatment with the external beam boron neutron capture therapy (BNCT) protocol were retrospectively analyzed. BSH (5 g/body) and BPA (250 mg/kg) based BNCT was performed in eight patients with newly diagnosed glioblastoma. The gross tumor volume (GTV) and clinical target volume (CTV)-1 were defined as the residual gadolinium-enhancing volume. CTV-2 and CTV-3 were defined as GTV plus a margin of 2 and 3 cm, respectively. As additional photon irradiation, a total X-ray dose of 30 Gy was given to the T2 high intensity area on MRI. Five of the eight patients were alive at analysis for a mean follow-up time of 20.3 months. The post-operative median survival time of the eight patients was 27.9 months (95% CI=21.0-34.8). The minimum tumor dose of GTV, CTV-2, and CTV-3 averaged 29.8{+-}9.9, 15.1{+-}5.4, and 12.4{+-}2.9 Gy, respectively. The minimum tumor non-boron dose of GTV, CTV-2, and CTV-3 averaged 2.0{+-}0.5, 1.3{+-}0.3, and 1.1{+-}0.2 Gy, respectively. The maximum normal brain dose, skin dose, and average brain dose were 11.4{+-}1.5, 9.6{+-}1.4, and 3.1{+-}0.4 Gy, respectively. The mean minimum dose at the failure site in cases of in-field recurrence (IR) and out-field recurrence (OR) was 26.3{+-}16.7 and 14.9 GyEq, respectively. The calculated doses at the failure site were at least equal to the tumor control doses which were previously reported. We speculate that the failure pattern was related to an inadequate distribution of boron-10. Further improvement of the microdistribution of boron compounds is expected, and may improve the tumor control by BNCT.

Fission reactor based epithermal neutron irradiation facilities for routine clinical application in BNCT-Hatanaka memorial lecture

International Nuclear Information System (INIS)

Harling, Otto K.

2009-01-01

Based on experience gained in the recent clinical studies at MIT/Harvard, the desirable characteristics of epithermal neutron irradiation facilities for eventual routine clinical BNCT are suggested. A discussion of two approaches to using fission reactors for epithermal neutron BNCT is provided. This is followed by specific suggestions for the performance and features needed for high throughput clinical BNCT. An example of a current state-of-the-art, reactor based facility, suited for routine clinical use is discussed. Some comments are provided on the current status of reactor versus accelerator based epithermal neutron sources for BNCT. This paper concludes with a summary and a few personal observations on BNCT by the author.

Boron neutron capture therapy for recurrent head and neck malignancies

International Nuclear Information System (INIS)

Kato, Itsuro; Ono, Koji; Sakurai, Yoshinori

2006-01-01

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

Evaluation of the characteristics of boron-dose enhancer (BDE) materials for BNCT using near threshold {sup 7}Li(p,n){sup 7}Be direct neutrons

Energy Technology Data Exchange (ETDEWEB)

Bengua, Gerard [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennann-gun, Osaka 590-0494 (Japan); Kobayashi, Tooru [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennann-gun, Osaka 590-0494 (Japan); Tanaka, Kenichi [Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi, Minami-ku, Hiroshima 734-8553 (Japan); Nakagawa, Yoshinobu [National Kagawa Children' s Hospital, Zentsuji-cho, Zentsuji, Kagawa 765-8501 (Japan)

2004-03-07

The characteristics of a number of candidate boron-dose enhancer (BDE) materials for boron neutron capture therapy (BNCT) using near threshold {sup 7}Li(p,n){sup 7}Be direct neutrons were evaluated based on the treatable protocol depth (TPD), defined in this paper. Simulation calculations were carried out by means of MCNP-4B transport code for candidate BDE materials, namely, (C{sub 2}H{sub 4}){sub n}, (C{sub 2}H{sub 3}F){sub n}, (C{sub 2}H{sub 2}F{sub 2}){sub n}, (C{sub 2}HF{sub 3}){sub n}, (C{sub 2}D{sub 4}){sub n}, (C{sub 2}F{sub 4}){sub n}, beryllium metal, graphite, D{sub 2}O and {sup 7}LiF. Dose protocols applied were those used for intra-operative BNCT treatment for brain tumour currently used in Japan. The maximum TPD (TPD{sub max}) for each BDE material was found to be between 4 cm and 5 cm in the order of (C{sub 2}H{sub 4}){sub n} < (C{sub 2}H{sub 3}F){sub n} < (C{sub 2}H{sub 2}F{sub 2}){sub n} < (C{sub 2}HF{sub 3}){sub n} < beryllium metal < (C{sub 2}D{sub 4}){sub n} < graphite < (C{sub 2}F{sub 4}){sub n} < D{sub 2}O < {sup 7}LiF. Based on the small and arbitrary variations in the TPD{sub max} for these materials, an explicit advantage of a candidate BDE material could not be established from the TPD{sub max} alone. The dependence of TPD on BDE thickness was found to be influenced by the type of BDE material. For materials with hydrogen, sharp variations in TPD were observed, while those without hydrogen exhibited more moderate fluctuations in TPD as the BDE thickness was varied. The BDE thickness corresponding to TPD{sub max} (BDE(TPD{sub max})) was also found to depend on the type of BDE material used. Thicker BDE(TPD{sub max}), obtained mostly for BDE materials without hydrogen, significantly reduced the dose rates within the phantom. The TPD{sub max}, the dependence of TPD on BDE thickness and the BDE (TPD{sub max}) were ascertained as appropriate optimization criteria in choosing suitable BDE materials for BNCT. Among the candidate BDE materials

Reprint of Application of BNCT to the treatment of HER2+ breast cancer recurrences: Research and developments in Argentina

International Nuclear Information System (INIS)

Gadan, M.A.; González, S.J.; Batalla, M.; Olivera, M.S.; Policastro, L.; Sztejnberg, M.L.

2015-01-01

In the frame of the Argentine BNCT Project a new research line has been started to study the application of BNCT to the treatment of locoregional recurrences of HER2+ breast cancer subtype. Based on former studies, the strategy considers the use of immunoliposomes as boron carriers nanovehicles to target HER2 overexpressing cells. The essential concerns of the current stage of this proposal are the development of carriers that can improve the efficiency of delivery of boron compounds and the dosimetric assessment of treatment feasibility. For this purpose, an specific pool of clinical cases that can benefit from this application was determined. In this work, we present the proposal and the advances related to the different stages of current research. - Highlights: • A new proposal of BNCT for HER2+ breast cancer treatment is introduced. • The proposal considers development of immunoliposomes as boron carrier nanovehicles. • Locoregional recurrences after treatment were identified as candidates for initial BNCT studies. • First analysis show acceptable neutron flux distributions provided by RA-6 BNCT facility.

INEL BNCT Research Program, May/June 1992

Energy Technology Data Exchange (ETDEWEB)

Venhuizen, J.R.

1992-09-01

This report presents summaries for two months of current research of the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murine screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor cell culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronophenylaianine (IBPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed.

INEL BNCT Research Program, September--October 1992

Energy Technology Data Exchange (ETDEWEB)

Venhuizen, J.R.

1992-12-01

This report presents summaries for two months of current research of the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murine screening experiments of low-density lipoprotain. carboranyl alanine, and liposome boron containing compounds. Pituitary tumor call culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronophonylalanine (BPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed.

INEL BNCT research program, July--August 1992

Energy Technology Data Exchange (ETDEWEB)

Venhuizen, J.R.

1992-10-01

This report presents summaries for two months of current research of the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murine screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor cell culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronophenylalanine (BPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed.

INEL BNCT Research Program, March/April 1992

Energy Technology Data Exchange (ETDEWEB)

Venhuizen, J.R.

1992-09-01

This report presents summaries for two months of current research for the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murino screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor call culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronopheoylalanine (BPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed.

INEL BNCT Research Program, September--October 1992

International Nuclear Information System (INIS)

Venhuizen, J.R.

1992-12-01

This report presents summaries for two months of current research of the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murine screening experiments of low-density lipoprotain. carboranyl alanine, and liposome boron containing compounds. Pituitary tumor call culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronophonylalanine (BPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed

INEL BNCT Research Program, January/February 1993

Energy Technology Data Exchange (ETDEWEB)

Venhuizen, J.R. [ed.

1993-04-01

This report presents summaries for two months of current research of the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murine screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor cell culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronophenylaianine (BPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed.

INEL BNCT Research Program, January/February 1993

International Nuclear Information System (INIS)

Venhuizen, J.R.

1993-04-01

This report presents summaries for two months of current research of the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murine screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor cell culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronophenylaianine (BPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed

INEL BNCT Research Program, May/June 1992

International Nuclear Information System (INIS)

Venhuizen, J.R.

1992-09-01

This report presents summaries for two months of current research of the Idaho National Engineering Laboratory (INEL) Boron Neutron Capture Therapy (BNCT) Program. Information is presented on development and murine screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor cell culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium (BSH) and boronophenylaianine (IBPA) are described. Treatment protocol development via the large animal (canine) model studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed

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

International Nuclear Information System (INIS)

Kobayashi, T.; Sakurai, Y.; Kanda, K.

2001-01-01

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)

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)

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Validation of dose planning calculations for boron neutron capture therapy using cylindrical and anthropomorphic phantoms

Energy Technology Data Exchange (ETDEWEB)

Koivunoro, Hanna; Seppaelae, Tiina; Uusi-Simola, Jouni; Merimaa, Katja; Savolainen, Sauli [Department of Physics, POB 64, FI-00014 University of Helsinki (Finland); Kotiluoto, Petri; Seren, Tom; Auterinen, Iiro [VTT Technical Research Centre of Finland, Espoo, POB 1000, FI-02044 VTT (Finland); Kortesniemi, Mika, E-mail: hanna.koivunoro@helsinki.f [HUS Helsinki Medical Imaging Center, University of Helsinki, POB 340, FI-00029 HUS (Finland)

2010-06-21

In this paper, the accuracy of dose planning calculations for boron neutron capture therapy (BNCT) of brain and head and neck cancer was studied at the FiR 1 epithermal neutron beam. A cylindrical water phantom and an anthropomorphic head phantom were applied with two beam aperture-to-surface distances (ASD). The calculations using the simulation environment for radiation application (SERA) treatment planning system were compared to neutron activation measurements with Au and Mn foils, photon dose measurements with an ionization chamber and the reference simulations with the MCNP5 code. Photon dose calculations using SERA differ from the ionization chamber measurements by 2-13% (disagreement increased along the depth in the phantom), but are in agreement with the MCNP5 calculations within 2%. The {sup 55}Mn(n,{gamma}) and {sup 197}Au(n,{gamma}) reaction rates calculated using SERA agree within 10% and 8%, respectively, with the measurements and within 5% with the MCNP5 calculations at depths >0.5 cm from the phantom surface. The {sup 55}Mn(n,{gamma}) reaction rate represents the nitrogen and boron depth dose within 1%. Discrepancy in the SERA fast neutron dose calculation (of up to 37%) is corrected if the biased fast neutron dose calculation option is not applied. Reduced voxel cell size ({<=}0.5 cm) improves the SERA calculation accuracy on the phantom surface. Despite the slight overestimation of the epithermal neutrons and underestimation of the thermal neutrons in the beam model, neutron calculation accuracy with the SERA system is sufficient for reliable BNCT treatment planning with the two studied treatment distances. The discrepancy between measured and calculated photon dose remains unsatisfactorily high for depths >6 cm from the phantom surface. Increasing discrepancy along the phantom depth is expected to be caused by the inaccurately determined effective point of the ionization chamber.

Logic Estimation of the Optimum Source Neutron Energy for BNCT of Brain Tumors

International Nuclear Information System (INIS)

Dorrah, M.A.; Gaber, F.A.; Abd Elwahab, M.A.; Kotb, M.A.; Mohammed, M.M.

2012-01-01

BNCT is very complicated technique; primarily due to the complexity of element composition of the brain. Moreover; numerous components contributes to the over all radiation dose both to normal brain and to tumor. Simple algebraic summation cannot be applied to these dose components, since each component should at first be weighed by its relative biological effectiveness (RBE) value. Unfortunately, there is no worldwide agreement on these RBE values. For that reason, the parameters required for accurate planning of BNCT of brain tumors located at different depths in brain remained obscure. The most important of these parameters is; the source neutron energy. Thermal neutrons were formerly employed for BNCT, but they failed to prove therapeutic efficacy. Later on; epithermal neutrons were suggested proposing that they would be enough thermalized while transporting in the brain tissues. However; debate aroused regarding the source neutrons energy appropriate for treating brain tumors located at different depths in brain. Again, the insufficient knowledge regarding the RBE values of the different dose components was a major obstacle. A new concept was adopted for estimating the optimum source neutrons energy appropriate for different circumstances of BNCT. Four postulations on the optimum source neutrons energy were worked out, almost entirely independent of the RBE values of the different dose components. Four corresponding condition on the optimum source neutrons energy were deduced. An energy escalation study was carried out investigating 65 different source neutron energies, between 0.01 eV and 13.2 MeV. MCNP4B Monte C arlo neutron transport code was utilized to study the behavior of neutrons in the brain. The deduced four conditions were applied to the results of the 65 steps of the neutron energy escalation study. A source neutron energy range of few electron volts (eV) to about 30 keV was estimated to be the most appropriate for BNCT of brain tumors located at

Tumor accumulation of {epsilon}-poly-lysines-based polyamines conjugated with boron clusters

Energy Technology Data Exchange (ETDEWEB)

Umano, Masayuki; Uechi, Kazuhiro; Uriuda, Takatoshi; Murayama, Sayuri; Azuma, Hideki [Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 5588585 (Japan); Shinohara, Atsuko [Department of Epidemiology and Environmental Health, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 1138421 (Japan); Liu, Young; Ono, Koji [Research Reactor Institute, Kyoto University, 2-1010 Asashiro-nishi, Kumatori 5900494 (Japan); Kirihata, Mitsunori [Department of Bioscience and Informatics, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai 5998531 (Japan); Yanagie, Hironobu [Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1138656 (Japan); Nagasaki, Takeshi, E-mail: nagasaki@bioa.eng.osaka-cu.ac.jp [Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 5588585 (Japan)

2011-12-15

Boron Neutron Capture Therapy (BNCT) is one of the potent cancer radiotherapies using nuclear reaction between {sup 10}B atoms and the neutron. Whether BNCT will succeed or not depends on tumor selective delivery of {sup 10}B compounds. {epsilon}-Poly-L-lysine is a naturally occurring polyamine characterized by the peptide linkages between the carboxyl and {epsilon}-amino groups of L-lysine. Because of high safety {epsilon}-PLL is applied practically as a food additive due to its strong antimicrobial activity. In this study, we focus on a development of a novel polymeric delivery system for BNCT using biodegradable {epsilon}-PLL conjugated with {sup 10}B-containing clusters (BSH). This polymeric boron carrier will be expected to deliver safely and efficiently into tumor tissues based on Enhanced Permeability and Retention (EPR) effect.

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

Science.gov (United States)

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

2017-02-01

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

Clinical requirements and accelerator concepts for BNCT

International Nuclear Information System (INIS)

Ludewigt, B.A.; Bleuel, D.L.; Chu, W.T.; Donahue, R.J.; Kwan, J.; Leung, K.N.; Reginato, L.L.; Wells, R.P.

1997-05-01

Accelerator-based neutron sources are an attractive alternative to nuclear reactors for providing epithermal neutron beams for Boron Neutron Capture Therapy. Based on clinical requirements and neutronics modeling the use of proton and deuteron induced reactions in 7 Li and 9 Be targets has been compared. Excellent epithermal neutron beams can be produced via the 7 Li(p,n) 7 Be reaction at proton energies of ∼2.5 MeV. An electrostatic quadrupole accelerator and a lithium target, which can deliver and handle 2.5 MeV protons at beam currents up to 50 mA, are under development for an accelerator-based BNCT facility at the Lawrence Berkeley National Laboratory

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)

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

2011-01-01

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

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

International Nuclear Information System (INIS)

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

2001-01-01

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

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

Science.gov (United States)

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

2011-12-01

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

INEL BNCT Program: Volume 5, No. 9. Bulletin, September 1991

Energy Technology Data Exchange (ETDEWEB)

Ackermann, A.L. [ed.

1991-12-31

This Bulletin presents a summary of accomplishments and highlights of the Idaho National Engineering Laboratory`s (INEL) Boron Neutron Capture Therapy (BNCT) Program for September 1991. This bulletin includes information on the brain tumor and melanoma research programs, Power Burst Facility (PBF) technical support and modifications, PBF operations, and updates to the animal data charts.

Radiation field characterization of a BNCT research facility using Monte Carlo Method - Code MCNP-4B

International Nuclear Information System (INIS)

Hernandes, Antonio Carlos

2002-01-01

Boron Neutron Capture Therapy - BNCT- is a selective cancer treatment and arises as an alternative therapy to treat cancer when usual techniques - surgery, chemotherapy or radiotherapy - show no satisfactory results. The main proposal of this work is to project a facility to BNCT studies. This facility relies on the use of an AmBe neutron source and on a set of moderators, filters and shielding which will provide the best neutron/gamma beam characteristic for these BNCT studies, i.e., high intensity thermal and/or epithermal neutron fluxes and with the minimum feasible gamma rays and fast neutrons contaminants. A computational model of the experiment was used to obtain the radiation field in the sample irradiation position. The calculations have been performed with the MCNP 4B Monte Carlo Code and the results obtained can be regarded as satisfactory, i.e., a thermal neutron fluency Ν Τ = 1,35x10 8 n/cm 2 , a fast neutron dose of 5,86x -1 0 Gy/Ν Τ and a gamma ray dose of 8,30x -14 Gy/Ν Τ . (author)

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

International Nuclear Information System (INIS)

Yanagie, H.; Yasuhara, H.; Ogura, K.; Maruyama, K.; Matsumoto, T.; Skvarc, J.; Ilic, R.; Kuhne, G.; Eriguchi, M.; Kobayashi, H.

2001-01-01

It is necessary to accumulate the 10 B atoms selectively to the tumor cells for effective boron neutron capture therapy (BNCT). In order to achieve accurate measurements of 10 B 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 10 B-polyethylene-glycol (PEG) binding liposome or 10 B-bare liposome. The 10 B 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 10 B 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, 10 B-PEG liposome is a candidate for an effective 10 B carrier in BNCT.(author)

Boron uptake measurements in metastatic tumours in rat lung

International Nuclear Information System (INIS)

Bortolussi, S.; Altieri, S.; Bruschi, P.

2006-01-01

Lung carcinoma is the leading cause of cancer mortality worldwide; despite the introduction over the last few years of new therapeutic agents, very little progress has been made in terms of survival, and the overall prognosis for these patients remains poor. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely and essential. To study the possibility to apply BNCT in the cure of diffuse pulmonary tumours, we created a BNCT Lung Project in Pavia, supported by Ministry of Education, University and Research (MIUR), in which Physicists, Medical Doctors and Biologists are involved. The first steps were; 1. development of an animal model for Boron uptake measurements in healthy and tumour lung tissues; 2. evaluation of the possibility to treat patients with epithermal neutron beams (See S. Altieri et al., this Conference); 3. in-vitro study of BNCT efficacy (see A. Zonta et al.). Spatial Boron distribution by neutron radiography in lung metastases from Colon Adenocarcinoma is reported; furthermore we present preliminary results of Boron concentration measures in rat lung tissues. The measures were performed using alpha spectrometry in thin tissue samples. (author)

First clinical results from the EORTC phase I Trial ''postoperative treatment of glioblastoma with BNCT at the Petten irradiation facility''

International Nuclear Information System (INIS)

Sauerwein, W.; Hideghety, K.; Rassow, J.; Devries, M.J.; Goetz, C.; Paquis, P.; Grochulla, F.; Wolbers, J.G.; Haselsberger, K.; Turowski, B.; Moss, R.L.; Stecher-Rasmussen, F.; Touw, D.; Wiestler, O.D.; Frankhauser, H.; Gabel, D.

2001-01-01

Based on the pre-clinical work of the European Collaboration on Boron Neutron Capture Therapy a study protocol was prepared in 1995 to initiate Boron Neutron Capture Therapy (BNCT) in patients at the High Flux Reactor (HFR) in Petten. Bio-distribution and pharmacokinetics data of the boron drug Na 2 B 12 H 11 SH (BSH) as well as the radiobiological effects of BNCT with BSH in healthy brain tissue of dogs were considered in designing the strategy for this clinical Phase I trial. The primary goal of the radiation dose escalation study is the investigation of possible adverse events due to BNCT; i.e. to establish the dose limiting toxicity and the maximal tolerated dose. The treatment is delivered in 4 fractions at a defined average boron concentration in blood. Cohorts of 10 patients are treated per dose group. The starting dose was set at 80% of the dose at which neurological symptoms occurred in preclinical dog experiments following a single fraction. After an observation period of at least 6 months, the dose is increased by 10% for the next cohort if less then three severe side effects related to the treatment occurred. The results of the first cohort are presented here. The evaluated dose level can be considered safe. (author)

First clinical results from the EORTC phase I Trial ''postoperative treatment of glioblastoma with BNCT at the Petten irradiation facility''

Energy Technology Data Exchange (ETDEWEB)

Sauerwein, W; Hideghety, K; Rassow, J [Department of Radiotherapy, University of Essen (Germany); Devries, M J [NDDO Oncology, Amsterdam (Netherlands); Goetz, C [Neurochirurgische Klinik, Klinikum Grosshadern Muenchen, Munich (Germany); Paquis, P [Dept. de Neurochirurgie, Hopital Pasteur, Nice (France); Grochulla, F [Klinik fuer Neurochirurgie, Zentralkrankenhaus Bremen (Germany); Wolbers, J G [Department of Neurosurgery, University Hospital ' ' Vrije Universiteit' ' , Amsterdam (Netherlands); Haselsberger, K [Klinik fuer Neurochirurgie, Karl-Franzens-Universitaet, Graz (Austria); Turowski, B [Institut fuer Neuroradiologie, Johann-Wolfgang-von-Goethe-Universitaet, Frankfurt (Germany); Moss, R L [HFR Unit, Joint Research Centre, European Commission, Petten (Netherlands); Stecher-Rasmussen, F [Nuclear Research and Consultancy Group NRG, Petten (Netherlands); Touw, D [Pharmacy, University/Academic Hospital ' ' Vrije Universiteit' ' , Amsterdam (Netherlands); Wiestler, O D [Department of Neuropathology, German Brain Tumour Reference Centre, Universitaetsklinikum Bonn (Germany); Frankhauser, H [Service de Neurochirurgie CHUV, Lausanne (Switzerland); Gabel, D [Chemistry Department, University of Bremen (Germany)

2001-05-01

Based on the pre-clinical work of the European Collaboration on Boron Neutron Capture Therapy a study protocol was prepared in 1995 to initiate Boron Neutron Capture Therapy (BNCT) in patients at the High Flux Reactor (HFR) in Petten. Bio-distribution and pharmacokinetics data of the boron drug Na{sub 2}B{sub 12}H{sub 11}SH (BSH) as well as the radiobiological effects of BNCT with BSH in healthy brain tissue of dogs were considered in designing the strategy for this clinical Phase I trial. The primary goal of the radiation dose escalation study is the investigation of possible adverse events due to BNCT; i.e. to establish the dose limiting toxicity and the maximal tolerated dose. The treatment is delivered in 4 fractions at a defined average boron concentration in blood. Cohorts of 10 patients are treated per dose group. The starting dose was set at 80% of the dose at which neurological symptoms occurred in preclinical dog experiments following a single fraction. After an observation period of at least 6 months, the dose is increased by 10% for the next cohort if less then three severe side effects related to the treatment occurred. The results of the first cohort are presented here. The evaluated dose level can be considered safe. (author)

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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 ...

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

Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours

International Nuclear Information System (INIS)

Sakurai, Yoshinori; Ono, Koji; Miyatake, Shin-ichi; Maruhashi, Akira

2006-01-01

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

Improvement effect on the depth-dose distribution by CSF drainage and air infusion of a tumour-removed cavity in boron neutron capture therapy for malignant brain tumours

Science.gov (United States)

Sakurai, Yoshinori; Ono, Koji; Miyatake, Shin-ichi; Maruhashi, Akira

2006-03-01

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

Boronated monoclonal antibody 225.28S for potential use in neutron capture therapy of malignant melanoma

International Nuclear Information System (INIS)

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

1989-01-01

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

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.

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

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.

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

International Nuclear Information System (INIS)

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

2006-01-01

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

High neutronic efficiency, low current targets for accelerator-based BNCT applications

International Nuclear Information System (INIS)

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

1998-01-01

The neutronic efficiency of target/filters for accelerator-based BNCT applications is measured by the proton current required to achieve a desirable neutron current at the treatment port (10 9 n/cm 2 /s). In this paper the authors describe two possible targeyt/filter concepts wihch minimize the required current. Both concepts are based on the Li-7 (p,n)Be-7 reaction. Targets that operate near the threshold energy generate neutrons that are close tothe desired energy for BNCT treatment. Thus, the filter can be extremely thin (∼ 5 cm iron). However, this approach has an extremely low neutron yield (n/p ∼ 1.0(-6)), thus requiring a high proton current. The proposed solutino is to design a target consisting of multiple extremely thin targets (proton energy loss per target ∼ 10 keV), and re-accelerate the protons between each target. Targets operating at ihgher proton energies (∼ 2.5 MeV) have a much higher yield (n/p ∼ 1.0(-4)). However, at these energies the maximum neutron energy is approximately 800 keV, and thus a neutron filter is required to degrade the average neutron energy to the range of interest for BNCT (10--20 keV). A neutron filter consisting of fluorine compounds and iron has been investigated for this case. Typically a proton current of approximately 5 mA is required to generate the desired neutron current at the treatment port. The efficiency of these filter designs can be further increased by incorporating neutron reflectors that are co-axial with the neutron source. These reflectors are made of materials which have high scattering cross sections in the range 0.1--1.0 MeV

Radiobiology of BNCT mediated by GB-10 and GB-10+BPA in experimental oral cancer

Energy Technology Data Exchange (ETDEWEB)

Trivillin, Veronica A.; Heber, Elisa M.; Itoiz, Maria E.; Nigg, David; Calzetta, Osvaldo; Blaumann, Herman; Longhino, Juan; Schwint, Amanda E. E-mail: schwint@cnea.gov.ar

2004-11-01

We previously reported biodistribution and pharmacokinetic data for GB-10 (Na{sub 2}{sup 10}B{sub 10}H{sub 10}) and the combined administration of GB-10 and boronophenylalanine (BPA) as boron delivery agents for boron neutron capture therapy (BNCT) in the hamster cheek pouch oral cancer model. The aim of the present study was to assess, for the first time, the response of hamster cheek pouch tumors, precancerous tissue and normal tissue to BNCT mediated by GB-10 and BNCT mediated by GB-10 and BPA administered jointly using the thermalized epithermal beam of the RA-6 Reactor at the Bariloche Atomic Center. GB-10 exerted 75.5% tumor control (partial+complete remission) with no damage to precancerous tissue around tumor or to normal tissue. Thus, GB-10 proved to be a therapeutically efficient boron agent in this model despite the fact that it is not taken up selectively by oral tumor tissue. GB-10 exerted a selective effect on tumor blood vessels leading to significant tumor control with a sparing effect on normal tissue. BNCT mediated by the combined administration of GB-10 and BPA resulted in a reduction in the dose to normal tissue and would thus allow for significant escalation of dose to tumor without exceeding normal tissue tolerance.

Radiobiology of BNCT mediated by GB-10 and GB-10+BPA in experimental oral cancer

International Nuclear Information System (INIS)

Trivillin, Veronica A.; Heber, Elisa M.; Itoiz, Maria E.; Nigg, David; Calzetta, Osvaldo; Blaumann, Herman; Longhino, Juan; Schwint, Amanda E.

2004-01-01

We previously reported biodistribution and pharmacokinetic data for GB-10 (Na 2 10 B 10 H 10 ) and the combined administration of GB-10 and boronophenylalanine (BPA) as boron delivery agents for boron neutron capture therapy (BNCT) in the hamster cheek pouch oral cancer model. The aim of the present study was to assess, for the first time, the response of hamster cheek pouch tumors, precancerous tissue and normal tissue to BNCT mediated by GB-10 and BNCT mediated by GB-10 and BPA administered jointly using the thermalized epithermal beam of the RA-6 Reactor at the Bariloche Atomic Center. GB-10 exerted 75.5% tumor control (partial+complete remission) with no damage to precancerous tissue around tumor or to normal tissue. Thus, GB-10 proved to be a therapeutically efficient boron agent in this model despite the fact that it is not taken up selectively by oral tumor tissue. GB-10 exerted a selective effect on tumor blood vessels leading to significant tumor control with a sparing effect on normal tissue. BNCT mediated by the combined administration of GB-10 and BPA resulted in a reduction in the dose to normal tissue and would thus allow for significant escalation of dose to tumor without exceeding normal tissue tolerance

New EORTC clinical trials for BNCT

International Nuclear Information System (INIS)

Hideghety, K.; Moss, R.; Vries, M. de

2000-01-01

Due to ethical reasons, a separated optimization of the two components of BNCT in the frame of clinical investigations can only be performed applying the whole binary system. The ongoing trial at HFR (High Flux Reactor Petten) has proven the feasibility of BNCT under defined conditions. On that basis the European Commission supported a comprehensive research project on boron imaging including three further clinical studies. In the first trial the boron uptake related to the blood boron concentration and surrounding normal tissue in various solid tumours will be examined using BSH (Sodiumborocaptate), BPA (Boronophenylalanine) or both in order to explore tumour entities, which may gain benefit from BNCT. The major objectives of the second trial are to define the maximum tolerated single and cumulative dose, and the dose limiting toxicity of BSH. The third clinical trial, a phase II study is designed to evaluate the anti-tumour effect of fractionated BNCT at the Petten treatment facility against cerebral metastasis of malignant melanoma using BPA. (author)

Design and optimization of a beam-shaping assembly (BSA) for BNCT based on a neutron generator located at CEADEN, Havana, Cuba

International Nuclear Information System (INIS)

Padilla Cabal, F.; Martin, G; Abrahantes, A.

2007-01-01

A monoenergetic neutron beam simulation study is carried out to determine the most suitable neutron energy for treatment of shallow and deep-seated brain tumors in the context of Boron Neutron Capture Therapy (BNCT). Two figures-of-merit, i.e. the absorbed dose for healthy tissue and the absorbed tumor dose at a given depth in the brain are used to measure the neutron beam quality. Also irradiation time, therapeutic gain and the power generated in the target are utilized as beam assessment parameters. Moderators, reflectors and delimiters are designed and optimized to moderate the high-energy neutrons from the fusion reactions 2 H(d;n) 3 He and 3 H(d;n) 4 He down to a suitable energy spectrum. Metallic uranium and manganese are successfully tested for fast-to-epithermal neutron moderation as well as Fluental TM for the neutron spectrum shifting. A semispherical target is proposed in order to dissipate twice the amount of power generated in the target, and decrease all the dimensions of the BSA. The cooling system of the target is also included in the calculations. Calculations are performed using the MCNP code. After the optimization of our beam-shaper a study of the dose distribution in the head had been made. The therapeutic gain is increased in 9% while the current required for one hour treatment is decreased in comparison with the trading prototypes of NG used for BNCT. (Author)

Design and optimization of a beam-shaping assembly (BSA) for BNCT based on a neutron generator located at CEADEN, Havana, Cuba