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

PubMed

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

2015-02-22

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

Workshop on neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fairchild, R.G.; Bond, V.P.

1986-01-01

Potentially optimal conditions for Neutron Capture Therapy (NCT) may soon be in hand due to the anticipated development of band-pass filtered beams relatively free of fast neutron contaminations, and of broadly applicable biomolecules for boron transport such as porphyrins and monoclonal antibodies. Consequently, a number of groups in the US are now devoting their efforts to exploring NCT for clinical application. The purpose of this Workshop was to bring these groups together to exchange views on significant problems of mutual interest, and to assure a unified and effective approach to the solutions. Several areas of preclinical investigation were deemed tomore » be necessary before it would be possible to initiate clinical studies. As neither the monomer nor the dimer of sulfhydryl boron hydride is unequivocally preferable at this time, studies on both compounds should be continued until one is proven superior.« less

Boron neutron capture therapy: Moving toward targeted cancer therapy.

PubMed

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

2016-01-01

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

Boron containing compounds and their preparation and use in neutron capture therapy

DOEpatents

Gabel, D.

1992-09-01

The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

Boron Neutron Capture Therapy - A Literature Review

PubMed Central

Nedunchezhian, Kavitaa; Thiruppathy, Manigandan; Thirugnanamurthy, Sarumathi

2016-01-01

Boron Neutron Capture Therapy (BNCT) is a radiation science which is emerging as a hopeful tool in treating cancer, by selectively concentrating boron compounds in tumour cells and then subjecting the tumour cells to epithermal neutron beam radiation. BNCT bestows upon the nuclear reaction that occurs when Boron-10, a stable isotope, is irradiated with low-energy thermal neutrons to yield α particles (Helium-4) and recoiling lithium-7 nuclei. A large number of 10 Boron (10B) atoms have to be localized on or within neoplastic cells for BNCT to be effective, and an adequate number of thermal neutrons have to be absorbed by the 10B atoms to maintain a lethal 10B (n, α) lithium-7 reaction. The most exclusive property of BNCT is that it can deposit an immense dose gradient between the tumour cells and normal cells. BNCT integrates the fundamental focusing perception of chemotherapy and the gross anatomical localization proposition of traditional radiotherapy. PMID:28209015

Boron Neutron Capture Therapy for Malignant Brain Tumors

PubMed Central

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

2016-01-01

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

Boron Neutron Capture Therapy for Malignant Brain Tumors.

PubMed

Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

2016-07-15

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

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

PubMed

Haapaniemi, Aaro; Kankaanranta, Leena; Saat, Riste; Koivunoro, Hanna; Saarilahti, Kauko; Mäkitie, Antti; Atula, Timo; Joensuu, Heikki

2016-05-01

To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer. 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. 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. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

Iodine neutron capture therapy

NASA Astrophysics Data System (ADS)

Ahmed, Kazi Fariduddin

A new technique, Iodine Neutron Capture Therapy (INCT) is proposed to treat hyperthyroidism in people. Present thyroid therapies, surgical removal and 131I treatment, result in hypothyroidism and, for 131I, involve protracted treatment times and excessive whole-body radiation doses. The new technique involves using a low energy neutron beam to convert a fraction of the natural iodine stored in the thyroid to radioactive 128I, which has a 24-minute half-life and decays by emitting 2.12-MeV beta particles. The beta particles are absorbed in and damage some thyroid tissue cells and consequently reduce the production and release of thyroid hormones to the blood stream. Treatment times and whole-body radiation doses are thus reduced substantially. This dissertation addresses the first of the several steps needed to obtain medical profession acceptance and regulatory approval to implement this therapy. As with other such programs, initial feasibility is established by performing experiments on suitable small mammals. Laboratory rats were used and their thyroids were exposed to the beta particles coming from small encapsulated amounts of 128I. Masses of 89.0 mg reagent-grade elemental iodine crystals have been activated in the ISU AGN-201 reactor to provide 0.033 mBq of 128I. This activity delivers 0.2 Gy to the thyroid gland of 300-g male rats having fresh thyroid tissue masses of ˜20 mg. Larger iodine masses are used to provide greater doses. The activated iodine is encapsulated to form a thin (0.16 cm 2/mg) patch that is then applied directly to the surgically exposed thyroid of an anesthetized rat. Direct neutron irradiation of a rat's thyroid was not possible due to its small size. Direct in-vivo exposure of the thyroid of the rat to the emitted radiation from 128I is allowed to continue for 2.5 hours (6 half-lives). Pre- and post-exposure blood samples are taken to quantify thyroid hormone levels. The serum T4 concentration is measured by radioimmunoassay at

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haapaniemi, Aaro, E-mail: aaro.haapaniemi@hus.fi; Kankaanranta, Leena; Saat, Riste

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 patientsmore » 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.« less

Neutron therapy of cancer

NASA Technical Reports Server (NTRS)

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

1969-01-01

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

Perspectives of boron-neutron capture therapy of malignant brain tumors

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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

2017-12-01

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

Accelerator-based neutron source for boron neutron capture therapy (BNCT) and method

DOEpatents

Yoon, W.Y.; Jones, J.L.; Nigg, D.W.; Harker, Y.D.

1999-05-11

A source for boron neutron capture therapy (BNCT) comprises a body of photoneutron emitter that includes heavy water and is closely surrounded in heat-imparting relationship by target material; one or more electron linear accelerators for supplying electron radiation having energy of substantially 2 to 10 MeV and for impinging such radiation on the target material, whereby photoneutrons are produced and heat is absorbed from the target material by the body of photoneutron emitter. The heavy water is circulated through a cooling arrangement to remove heat. A tank, desirably cylindrical or spherical, contains the heavy water, and a desired number of the electron accelerators circumferentially surround the tank and the target material as preferably made up of thin plates of metallic tungsten. Neutrons generated within the tank are passed through a surrounding region containing neutron filtering and moderating materials and through neutron delimiting structure to produce a beam or beams of epithermal neutrons normally having a minimum flux intensity level of 1.0{times}10{sup 9} neutrons per square centimeter per second. Such beam or beams of epithermal neutrons are passed through gamma ray attenuating material to provide the required epithermal neutrons for BNCT use. 3 figs.

Accelerator-based neutron source for boron neutron capture therapy (BNCT) and method

DOEpatents

Yoon, Woo Y.; Jones, James L.; Nigg, David W.; Harker, Yale D.

1999-01-01

A source for boron neutron capture therapy (BNCT) comprises a body of photoneutron emitter that includes heavy water and is closely surrounded in heat-imparting relationship by target material; one or more electron linear accelerators for supplying electron radiation having energy of substantially 2 to 10 MeV and for impinging such radiation on the target material, whereby photoneutrons are produced and heat is absorbed from the target material by the body of photoneutron emitter. The heavy water is circulated through a cooling arrangement to remove heat. A tank, desirably cylindrical or spherical, contains the heavy water, and a desired number of the electron accelerators circumferentially surround the tank and the target material as preferably made up of thin plates of metallic tungsten. Neutrons generated within the tank are passed through a surrounding region containing neutron filtering and moderating materials and through neutron delimiting structure to produce a beam or beams of epithermal neutrons normally having a minimum flux intensity level of 1.0.times.10.sup.9 neutrons per square centimeter per second. Such beam or beams of epithermal neutrons are passed through gamma ray attenuating material to provide the required epithermal neutrons for BNCT use.

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

PubMed Central

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

2015-01-01

Abstract Phantom experiments to evaluate thermal neutron flux distribution were performed using the Scintillator with Optical Fiber (SOF) detector, which was developed as a thermal neutron monitor during boron neutron capture therapy (BNCT) irradiation. Compared with the gold wire activation method and Monte Carlo N-particle (MCNP) calculations, it was confirmed that the SOF detector is capable of measuring thermal neutron flux as low as 105 n/cm2/s with sufficient accuracy. The SOF detector will be useful for phantom experiments with BNCT neutron fields from low-current accelerator-based neutron sources. PMID:25589504

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1996-12-31

Boron neutron capture therapy (BNCT) is a bimodal form of radiation therapy for cancer. The first component of this treatment is the preferential localization of the stable isotope {sup 10}B in tumor cells by targeting with boronated compounds. The tumor and surrounding tissue is then irradiated with a neutron beam resulting in thermal neutron/{sup 10}B reactions ({sup 10}B(n,{alpha}){sup 7}Li) resulting in the production of localized high LET radiation from alpha and {sup 7}Li particles. These products of the neutron capture reaction are very damaging to cells, but of short range so that the majority of the ionizing energy released ismore » 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.« less

Proceedings of the first international symposium on neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fairchild, R.G.; Brownell, G.L.

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

In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent.

PubMed

Dewi, Novriana; Mi, Peng; Yanagie, Hironobu; Sakurai, Yuriko; Morishita, Yasuyuki; Yanagawa, Masashi; Nakagawa, Takayuki; Shinohara, Atsuko; Matsukawa, Takehisa; Yokoyama, Kazuhito; Cabral, Horacio; Suzuki, Minoru; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Nishiyama, Nobuhiro; Kataoka, Kazunori; Takahashi, Hiroyuki

2016-04-01

A more immediate impact for therapeutic approaches of current clinical research efforts is of major interest, which might be obtained by developing a noninvasive radiation dose-escalation strategy, and neutron capture therapy represents one such novel approach. Furthermore, some recent researches on neutron capture therapy have focused on using gadolinium as an alternative or complementary for currently used boron, taking into account several advantages that gadolinium offers. Therefore, in this study, we carried out feasibility evaluation for both single and multiple injections of gadolinium-based MRI contrast agent incorporated in calcium phosphate nanoparticles as neutron capture therapy agent. In vivo evaluation was performed on colon carcinoma Col-26 tumor-bearing mice irradiated at nuclear reactor facility of Kyoto University Research Reactor Institute with average neutron fluence of 1.8 × 10(12) n/cm(2). Antitumor effectivity was evaluated based on tumor growth suppression assessed until 27 days after neutron irradiation, followed by histopathological analysis on tumor slice. The experimental results showed that the tumor growth of irradiated mice injected beforehand with Gd-DTPA-incorporating calcium phosphate-based nanoparticles was suppressed up to four times higher compared to the non-treated group, supported by the results of histopathological analysis. The results of antitumor effectivity observed on tumor-bearing mice after neutron irradiation indicated possible effectivity of gadolinium-based neutron capture therapy treatment.

Geant4 beam model for boron neutron capture therapy: investigation of neutron dose components.

PubMed

Moghaddasi, Leyla; Bezak, Eva

2018-03-01

Boron neutron capture therapy (BNCT) is a biochemically-targeted type of radiotherapy, selectively delivering localized dose to tumour cells diffused in normal tissue, while minimizing normal tissue toxicity. BNCT is based on thermal neutron capture by stable [Formula: see text]B nuclei resulting in emission of short-ranged alpha particles and recoil [Formula: see text]Li nuclei. The purpose of the current work was to develop and validate a Monte Carlo BNCT beam model and to investigate contribution of individual dose components resulting of neutron interactions. A neutron beam model was developed in Geant4 and validated against published data. The neutron beam spectrum, obtained from literature for a cyclotron-produced beam, was irradiated to a water phantom with boron concentrations of 100 μg/g. The calculated percentage depth dose curves (PDDs) in the phantom were compared with published data to validate the beam model in terms of total and boron depth dose deposition. Subsequently, two sensitivity studies were conducted to quantify the impact of: (1) neutron beam spectrum, and (2) various boron concentrations on the boron dose component. Good agreement was achieved between the calculated and measured neutron beam PDDs (within 1%). The resulting boron depth dose deposition was also in agreement with measured data. The sensitivity study of several boron concentrations showed that the calculated boron dose gradually converged beyond 100 μg/g boron concentration. This results suggest that 100μg/g tumour boron concentration may be optimal and above this value limited increase in boron dose is expected for a given neutron flux.

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

NASA Astrophysics Data System (ADS)

Skalyga, V.; Izotov, I.; Golubev, S.; Razin, S.; Sidorov, A.; Maslennikova, A.; Volovecky, A.; Kalvas, T.; Koivisto, H.; Tarvainen, O.

2014-12-01

Boron-neutron capture therapy (BNCT) is a perspective treatment method for radiation resistant tumors. Unfortunately its development is strongly held back by a several physical and medical problems. Neutron sources for BNCT currently are limited to nuclear reactors and accelerators. For wide spread of BNCT investigations more compact and cheap neutron source would be much more preferable. In present paper an approach for compact D-D neutron generator creation based on a high current ECR ion source is suggested. Results on dense proton beams production are presented. A possibility of ion beams formation with current density up to 600 mA/cm2 is demonstrated. Estimations based on obtained experimental results show that neutron target bombarded by such deuteron beams would theoretically yield a neutron flux density up to 6·1010 cm-2/s. Thus, neutron generator based on a high-current deuteron ECR source with a powerful plasma heating by gyrotron radiation could fulfill the BNCT requirements significantly lower price, smaller size and ease of operation in comparison with existing reactors and accelerators.

Thiourea derivatives, methods of their preparation and their use in neutron capture therapy of malignant melanoma

DOEpatents

Gabel, D.

1991-06-04

The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

Tandem-ESQ for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreiner, A. J.; Escuela de Ciencia y Tecnologia, Universidad de Gral San Martin; CONICET,

2007-02-12

A folded tandem, with 1.25 MV terminal voltage, combined with an ElectroStatic Quadrupole (ESQ) chain is being proposed as a machine for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT). The machine is shown to be capable of accelerating a 30 mA proton beam to 2.5 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the on the 7Li(p,n)7Be reaction, to perform BNCT treatment for deep seated tumors in less than an hour.

Neutron capture therapy with deep tissue penetration using capillary neutron focusing

DOEpatents

Peurrung, Anthony J.

1997-01-01

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

Boron neutron capture therapy for recurrent high-grade meningiomas.

PubMed

Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Ono, Koji; Miyatake, Shin-Ichi

2013-10-01

Similar to glioblastomas, high-grade meningiomas are difficult pathologies to control. In this study, the authors used boron neutron capture therapy (BNCT), a tumor-selective intensive particle radiation modality, to treat high-grade meningioma. From June 2005 to September 2011, BNCT was applied 28 times in 20 cases of recurrent high-grade meningioma. All patients had previously undergone intensive treatments such as repetitive surgeries and multiple sessions of radiation therapy. Fluorine-18-labeled boronophenylalanine ((18)F-BPA) PET was performed before BNCT in 19 of the 20 cases; BPA is itself a therapeutic compound. Compound uptake, tumor shrinkage, long-term control rate including survival time, and failure pattern of the treated patients were all evaluated. Eighteen of 19 cases studied using (18)F-BPA PET showed good BPA uptake, with ratios of tumor to normal brain greater than 2.7. These ratios indicated the likely effects of BNCT prior to neutron irradiation. The original tumor sizes were between 4.3 cm(3) and 109 cm(3). A mean tumor volume reduction of 64.5% was obtained after BNCT within just 2 months. The median follow-up duration was 13 months. Six patients are still alive; at present, the median survival times after BNCT and diagnosis are 14.1 months (95% CI 8.6-40.4 months) and 45.7 months (95% CI 32.4-70.7 months), respectively. Clinical symptoms before BNCT, such as hemiparesis and facial pain, were improved after BNCT in symptomatic cases. Systemic metastasis, intracranial distant recurrence outside the radiation field, CSF dissemination, and local tumor progression were observed in 6, 7, 3, and 3 cases, respectively, during the clinical course. Apparent pseudoprogression was observed in at least 3 cases. Symptomatic radiation injuries occurred in 6 cases, and were controllable in all but 1 case. Boron neutron capture therapy may be especially effective in cases of high-grade meningioma.

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

PubMed

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

2016-05-01

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

Neutron capture therapy with deep tissue penetration using capillary neutron focusing

DOEpatents

Peurrung, A.J.

1997-08-19

An improved method is disclosed for delivering thermal neutrons to a subsurface cancer or tumor which has been first doped with a dopant having a high cross section for neutron capture. The improvement is the use of a guide tube in cooperation with a capillary neutron focusing apparatus, or neutron focusing lens, for directing neutrons to the tumor, and thereby avoiding damage to surrounding tissue. 1 fig.

[Possibilities of boron neutron capture therapy in the treatment of malignant brain tumors].

PubMed

Kanygin, V V; Kichigin, A I; Gubanova, N V; Taskaev, S Yu

2015-01-01

Boron neutron capture therapy (BNCT) that is of the highest attractiveness due to its selective action directly on malignant tumor cells is a promising approach to treating cancers. Clinical interest in BNCT focuses in neuro-oncology on therapy for gliomas, glioblastoma in particular, and BNCT may be used in brain metastatic involvement. This needs an epithermal neutron source that complies with the requirements for BNCT, as well as a 10B-containing agent that will selectively accumulate in tumor tissue. The introduction of BNCT into clinical practice to treat patients with glial tumors will be able to enhance therapeutic efficiency.

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

NASA Astrophysics Data System (ADS)

Khorshidi, A.; Ghafoori-Fard, H.; Sadeghi, M.

2014-05-01

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

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

PubMed

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

2016-01-01

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

A comparison of the COG and MCNP codes in computational neutron capture therapy modeling, Part II: gadolinium neutron capture therapy models and therapeutic effects.

PubMed

Wangerin, K; Culbertson, C N; 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 gadolinium neutron capture therapy (GdNCT) related modeling. The validity of COG NCT model has been established for this model, and here the calculation was extended to analyze the effect of various gadolinium concentrations on dose distribution and cell-kill effect of the GdNCT modality and to determine the optimum therapeutic conditions for treating brain cancers. The computational results were compared with the widely used MCNP code. The differences between the COG and MCNP predictions were generally small and suggest that the COG code can be applied to similar research problems in NCT. Results for this study also showed that a concentration of 100 ppm gadolinium in the tumor was most beneficial when using an epithermal neutron beam.

Final Stage in the Design of a Boron Neutron Capture Therapy facility at CEADEN, Cuba

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cabal, F. Padilla; Martin, G.

A neutron beam simulation study is carried out to determine the most suitable neutron energy for treatment of shallow and deep-seated brain tumors in the context of Boron Neutron Capture Therapy (BNCT). Two figures-of-merit, the therapeutic gain and the neutron fluence are utilized as beam assessment parameters. An irradiation cavity is used instead of a parallel beam port for the therapy. Calculations are performed using the MCNP5 code. After the optimization of our beam-shaper a study of the dose distribution in the head, neck, tyroids, lungs and upper and middle spine had been made. The therapeutic gain is increased whilemore » the current required for one hour treatment is decreased in comparison with the trading prototypes of NG used for BNCT.« less

Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

NASA Astrophysics Data System (ADS)

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

2010-08-01

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a real patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.

Treatment Planning for Accelerator-Based Boron Neutron Capture Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrera, Maria S.; Gonzalez, Sara J.; Minsky, Daniel M.

2010-08-04

Glioblastoma multiforme and metastatic melanoma are frequent brain tumors in adults and presently still incurable diseases. Boron Neutron Capture Therapy (BNCT) is a promising alternative for this kind of pathologies. Accelerators have been proposed for BNCT as a way to circumvent the problem of siting reactors in hospitals and for their relative simplicity and lower cost among other advantages. Considerable effort is going into the development of accelerator-based BNCT neutron sources in Argentina. Epithermal neutron beams will be produced through appropriate proton-induced nuclear reactions and optimized beam shaping assemblies. Using these sources, computational dose distributions were evaluated in a realmore » patient with diagnosed glioblastoma treated with BNCT. The simulated irradiation was delivered in order to optimize dose to the tumors within the normal tissue constraints. Using Monte Carlo radiation transport calculations, dose distributions were generated for brain, skin and tumor. Also, the dosimetry was studied by computing cumulative dose-volume histograms for volumes of interest. The results suggest acceptable skin average dose and a significant dose delivered to tumor with low average whole brain dose for irradiation times less than 60 minutes, indicating a good performance of an accelerator-based BNCT treatment.« less

Application of boronated anti-CEA immunoliposome to tumour cell growth inhibition in in vitro boron neutron capture therapy model.

PubMed Central

Yanagië, H.; Tomita, T.; Kobayashi, H.; Fujii, Y.; Takahashi, T.; Hasumi, K.; Nariuchi, H.; Sekiguchi, M.

1991-01-01

An immunoliposome containing a 10B-compound has been examined as a selective drug delivery system in boron neutron-capture therapy. Liposomes, conjugated with monoclonal antibodies specific for carcinoembryonic antigen (CEA) were shown to bind selectively to cells bearing CEA on their surface. The immunoliposomes attached to tumour cells suppressed growth in vitro upon thermal neutron irradiation and suppression was dependent upon the concentration of the 10B-compound in the liposomes and on the density of antibody conjugated to the liposomes. The results suggest that immunoliposomes containing the 10B-compound could act as a selective and efficient carrier of 10B atoms to target tumour cells in boron neutron-capture therapy. Images Figure 1 PMID:2021537

MAGIC polymer gel for dosimetric verification in boron neutron capture therapy

PubMed Central

Heikkinen, Sami; Kotiluoto, Petri; Serén, Tom; Seppälä, Tiina; Auterinen, Iiro; Savolainen, Sauli

2007-01-01

Radiation‐sensitive polymer gels are among the most promising three‐dimensional dose verification tools developed to date. We tested the normoxic polymer gel dosimeter known by the acronym MAGIC (methacrylic and ascorbic acid in gelatin initiated by copper) to evaluate its use in boron neutron capture therapy (BNCT) dosimetry. We irradiated a large cylindrical gel phantom (diameter: 10 cm; length: 20 cm) in the epithermal neutron beam of the Finnish BNCT facility at the FiR 1 nuclear reactor. Neutron irradiation was simulated with a Monte Carlo radiation transport code MCNP. To compare dose–response, gel samples from the same production batch were also irradiated with 6 MV photons from a medical linear accelerator. Irradiated gel phantoms then underwent magnetic resonance imaging to determine their R2 relaxation rate maps. The measured and normalized dose distribution in the epithermal neutron beam was compared with the dose distribution calculated by computer simulation. The results support the feasibility of using MAGIC gel in BNCT dosimetry. PACS numbers: 87.53.Qc, 87.53.Wz, 87.66.Ff PMID:17592463

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

NASA Astrophysics Data System (ADS)

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

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

Development of real-time thermal neutron monitor using boron-loaded plastic scintillator with optical fiber for boron neutron capture therapy.

PubMed

Ishikawa, M; Ono, K; Sakurai, Y; Unesaki, H; Uritani, A; Bengua, G; Kobayashi, T; Tanaka, K; Kosako, T

2004-11-01

A new thermal neutron monitor for boron neutron capture therapy was developed in this study. We called this monitor equipped boron-loaded plastic scintillator that uses optical fiber for signal transmission as an [scintillator with optical fiber] SOF detector. A water phantom experiment was performed to verify how the SOF detector compared with conventional method of measuring thermal neutron fluence. Measurements with a single SOF detector yielded indistinguishable signals for thermal neutrons and gamma rays. To account for the gamma ray contribution in the signal recorded by the SOF detector, a paired SOF detector system was employed. This was composed of an SOF detector with boron-loaded scintillator and an SOF detector with a boron-free scintillator. The difference between the recorded counts of these paired SOF detectors was used as the measure of the gamma ray contribution in the measured neutron fluence. The paired SOF detectors were ascertained to be effective in measuring thermal neutron flux in the range above 10(6)(n/cm(2)/s). Clinical trials using paired SOF to measure thermal neutron flux during therapy confirmed that paired SOF detectors were effective as a real-time thermal neutron flux monitor.

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

PubMed

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

2014-10-01

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

Study on High Speed Lithium Jet For Neutron Source of Boron Neutron Capture Therapy (BNCT)

NASA Astrophysics Data System (ADS)

Takahashi, Minoru; Kobayashi, Tooru; Zhang, Mingguang; Mák, Michael; Štefanica, Jirí; Dostál, Václav; Zhao, Wei

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.

Characteristics of a heavy water photoneutron source in boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Danial, Salehi; Dariush, Sardari; M. Salehi, Jozani

2013-07-01

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

Intracellular delivery and passive tumor targeting of a self-assembled nanogel containing carborane clusters for boron neutron capture therapy.

PubMed

Kawasaki, Riku; Sasaki, Yoshihiro; Akiyoshi, Kazunari

2017-01-29

Boron neutron capture therapy, based on the release of thermal neutron irradiation from boron, is a targeted radiation therapy for cancer. Targeted and sufficient accumulation of boron in tumor cells to achieve cytotoxic efficacy and reduce off-target effects remains a challenge. Carborane has been investigated for use as a delivery agent in boron neutron capture therapy because of its high boron content and chemical stability; however, it is cytotoxic, making safe delivery difficult. The aim of this study was to investigate the potential of carborane-bearing pullulan nanogels to safely and effectively deliver boron to tumor cells in vitro and in vivo and, consequently, assess their potential as a boron neutron capture therapeutic. Murine fibrosarcoma cells (CMS5a) were used for in vitro investigations of nanogel cytotoxicity, cell uptake. A mouse fibrosarcoma xenograft model was used to investigate the bio-distribution of nanogels after intravenous administration. The nanogels produced no apparent cytotoxicity and underwent cell uptake in CMS5a cells after a 24 h incubation at up to 2000 μg/mL and 400 μg/mL, respectively. The internalized nanogels were localized around the nuclear membrane. The nanogels were administered intravenously to mice bearing fibrosarcoma xenografts. Nanogel tumor localization likely occurred through the enhanced permeation and retention effect. The nanogels successfully reduced the cytotoxicity of carborane, were internalized into tumor cells, acted as a dual-delivery therapeutic and accumulated in tumors in vivo. Consequently, they demonstrate significant potential as a boron neutron capture therapeutic. Copyright © 2016 Elsevier Inc. All rights reserved.

Measurements of neutron distribution in neutrons-gamma-rays mixed field using imaging plate for neutron capture therapy.

PubMed

Tanaka, Kenichi; Endo, Satoru; Hoshi, Masaharu

2010-01-01

The imaging plate (IP) technique is tried to be used as a handy method to measure the spatial neutron distribution via the (157)Gd(n,gamma)(158)Gd reaction for neutron capture therapy (NCT). For this purpose, IP is set in a water phantom and irradiated in a mixed field of neutrons and gamma-rays. The Hiroshima University Radiobiological Research Accelerator is utilized for this experiment. The neutrons are moderated with 20-cm-thick D(2)O to obtain suitable neutron field for NCT. The signal for IP doped with Gd as a neutron-response enhancer is subtracted with its contribution by gamma-rays, which was estimated using IP without Gd. The gamma-ray response of Gd-doped IP to non-Gd IP is set at 1.34, the value measured for (60)Co gamma-rays, in estimating the gamma-ray contribution to Gd-doped IP signal. Then measured distribution of the (157)Gd(n,gamma)(158)Gd reaction rate agrees within 10% with the calculated value based on the method that has already been validated for its reproducibility of Au activation. However, the evaluated distribution of the (157)Gd(n,gamma)(158)Gd reaction rate is so sensitive to gamma-ray energy, e.g. the discrepancy of the (157)Gd(n,gamma)(158)Gd reaction rate between measurement and calculation becomes 30% for the photon energy change from 33keV to 1.253MeV.

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

NASA Astrophysics Data System (ADS)

Yamamoto, T.; Matsumura, A.; Yamamoto, K.; Kumada, H.; Shibata, Y.; Nose, T.

2002-07-01

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

A 13C(d,n)-based epithermal neutron source for Boron Neutron Capture Therapy.

PubMed

Capoulat, M E; Kreiner, A J

2017-01-01

Boron Neutron Capture Therapy (BNCT) requires neutron sources suitable for in-hospital siting. Low-energy particle accelerators working in conjunction with a neutron producing reaction are the most appropriate choice for this purpose. One of the possible nuclear reactions is 13 C(d,n) 14 N. The aim of this work is to evaluate the therapeutic capabilities of the neutron beam produced by this reaction, through a 30mA beam of deuterons of 1.45MeV. A Beam Shaping Assembly design was computationally optimized. Depth dose profiles in a Snyder head phantom were simulated with the MCNP code for a number of BSA configurations. In order to optimize the treatment capabilities, the BSA configuration was determined as the one that allows maximizing both the tumor dose and the penetration depth while keeping doses to healthy tissues under the tolerance limits. Significant doses to tumor tissues were achieved up to ∼6cm in depth. Peak doses up to 57Gy-Eq can be delivered in a fractionated scheme of 2 irradiations of approximately 1h each. In a single 1h irradiation, lower but still acceptable doses to tumor are also feasible. Treatment capabilities obtained here are comparable to those achieved with other accelerator-based neutron sources, making of the 13 C(d,n) 14 N reaction a realistic option for producing therapeutic neutron beams through a low-energy particle accelerator. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Intracellular delivery and passive tumor targeting of a self-assembled nanogel containing carborane clusters for boron neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawasaki, Riku; JST-ERATO, Japan Science and Technology Agency; Sasaki, Yoshihiro

Boron neutron capture therapy, based on the release of thermal neutron irradiation from boron, is a targeted radiation therapy for cancer. Targeted and sufficient accumulation of boron in tumor cells to achieve cytotoxic efficacy and reduce off-target effects remains a challenge. Carborane has been investigated for use as a delivery agent in boron neutron capture therapy because of its high boron content and chemical stability; however, it is cytotoxic, making safe delivery difficult. The aim of this study was to investigate the potential of carborane-bearing pullulan nanogels to safely and effectively deliver boron to tumor cells in vitro and in vivo and,more » consequently, assess their potential as a boron neutron capture therapeutic. Murine fibrosarcoma cells (CMS5a) were used for in vitro investigations of nanogel cytotoxicity, cell uptake. A mouse fibrosarcoma xenograft model was used to investigate the bio-distribution of nanogels after intravenous administration. The nanogels produced no apparent cytotoxicity and underwent cell uptake in CMS5a cells after a 24 h incubation at up to 2000 μg/mL and 400 μg/mL, respectively. The internalized nanogels were localized around the nuclear membrane. The nanogels were administered intravenously to mice bearing fibrosarcoma xenografts. Nanogel tumor localization likely occurred through the enhanced permeation and retention effect. The nanogels successfully reduced the cytotoxicity of carborane, were internalized into tumor cells, acted as a dual-delivery therapeutic and accumulated in tumors in vivo. Consequently, they demonstrate significant potential as a boron neutron capture therapeutic. - Highlights: • A carborane-bearing pullulan nanogel is developed as a boron delivery agent. • The nanogels are cell-friendly and show effective cell uptake for drug delivery. • The nanogels show passive tumor targeting by enhanced permeation and retention.« less

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

PubMed

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

2014-04-01

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

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

NASA Astrophysics Data System (ADS)

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

2009-06-01

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

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

PubMed

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

2015-12-01

The neutron source of BNCT is currently changing from reactor to accelerator, but peripheral facilities such as a dose-planning system and blood boron analysis have still not been established. To evaluate the potential application of particle-induced gamma-ray emission (PIGE) for boron measurement in clinical boron neutron capture therapy, boronophenylalanine dissolved within a cell culture medium was measured using PIGE. PIGE detected 18 μgB/mL f-BPA in the culture medium, and all measurements of any given sample were taken within 20 min. Two hours of f-BPA exposure was required to create a boron distribution image. However, even though boron remained in the cells, the boron on the cell membrane could not be distinguished from the boron in the cytoplasm. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC): application for photodynamic therapy and boron neutron capture therapy.

PubMed

Hiramatsu, Ryo; Kawabata, Shinji; Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Ono, Koji; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Hao, Erhong; Vicente, M Graça H

2015-03-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for Photodynamic Therapy and Boron Neutron Capture Therapy

PubMed Central

HIRAMATSU, RYO; KAWABATA, SHINJI; TANAKA, HIROKI; SAKURAI, YOSHINORI; SUZUKI, MINORU; ONO, KOJI; MIYATAKE, SHIN-ICHI; KUROIWA, TOSHIHIKO; HAO, ERHONG; VICENTE, M. GRAÇA H.

2015-01-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC’s applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm2) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 1012 n/cm2) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37–43 days). PMID:25546823

Boron neutron capture therapy for malignant melanoma: first clinical case report in China

PubMed Central

Yong, Zhong; Song, Zewen; Zhou, Yongmao; Liu, Tong; Zhang, Zizhu; Zhao, Yanzhong; Chen, Yang; Jin, Congjun; Chen, Xiang; Lu, Jianyun; Han, Rui; Li, Pengzhou; Sun, Xulong; Wang, Guohui; Shi, Guangqing; Zhu, Shaihong

2016-01-01

A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals. PMID:28174492

Sensitivity studies of beam directionality, beam size, and neutron spectrum for a fission converter-based epithermal neutron beam for boron neutron capture therapy.

PubMed

Sakamoto, S; Kiger, W S; Harling, O K

1999-09-01

Sensitivity studies of epithermal neutron beam performance in boron neutron capture therapy are presented for realistic neutron beams with varying filter/moderator and collimator/delimiter designs to examine the relative importance of neutron beam spectrum, directionality, and size. Figures of merit for in-air and in-phantom beam performance are calculated via the Monte Carlo technique for different well-optimized designs of a fission converter-based epithermal neutron beam with head phantoms as the irradiation target. It is shown that increasing J/phi, a measure of beam directionality, does not always lead to corresponding monotonic improvements in beam performance. Due to the relatively low significance, for most configurations, of its effect on in-phantom performance and the large intensity losses required to produce beams with very high J/phi, beam directionality should not be considered an important figure of merit in epithermal neutron beam design except in terms of its consequences on patient positioning and collateral dose. Hardening the epithermal beam spectrum, while maintaining the specific fast neutron dose well below the inherent hydrogen capture dose, improves beam penetration and advantage depth and, as a desirable by-product, significantly increases beam intensity. Beam figures of merit are shown to be strongly dependent on beam size relative to target size. Beam designs with J/phi approximately 0.65-0.7, specific fast neutron doses of 2-2.6x10(-13) Gy cm2/n and beam sizes equal to or larger than the size of the head target produced the deepest useful penetration, highest therapeutic ratios, and highest intensities.

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a monte carlo study.

PubMed

Jung, Joo-Young; Yoon, Do-Kun; Barraclough, Brendan; Lee, Heui Chang; Suh, Tae Suk; Lu, Bo

2017-06-13

The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy.

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a Monte Carlo study

PubMed Central

Barraclough, Brendan; Lee, Heui Chang; Suh, Tae Suk; Lu, Bo

2017-01-01

The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy. PMID:28427153

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

PubMed

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

2017-04-12

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

A theoretical model for the production of Ac-225 for cancer therapy by neutron capture transmutation of Ra-226.

PubMed

Melville, G; Melville, P

2013-02-01

Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation by bombarding Ra-226 with high-energy neutrons from a neutron source to produce Ra-225 and hence Ac-225, which can be used as a generator to produce Bi-213 for use in 'Targeted Alpha Therapy' for cancer. This paper examines the possibility of producing Ac-225 by neutron capture using a theoretical model in which neutron energy is convoluted with the corresponding neutron cross sections of Ra-226. The total integrated yield can then be obtained. This study shows that an intense beam of high-energy neutrons could initiate neutron capture on Ra-226 to produce Ra-225 and hence practical amounts of Ac-225 and a useful reduction of Ra-226. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

Blue, Thomas E; Yanch, Jacquelyn C

2003-01-01

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

Neutron capture reactions at DANCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bredeweg, T. A.

2008-05-12

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

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

PubMed

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

2016-03-01

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

Accelerator driven neutron source design via beryllium target and 208Pb moderator for boron neutron capture therapy in alternative treatment strategy by Monte Carlo method.

PubMed

Khorshidi, Abdollah

2017-01-01

The reactor has increased its area of application into medicine especially boron neutron capture therapy (BNCT); however, accelerator-driven neutron sources can be used for therapy purposes. The present study aimed to discuss an alternative method in BNCT functions by a small cyclotron with low current protons based on Karaj cyclotron in Iran. An epithermal neutron spectrum generator was simulated with 30 MeV proton energy for BNCT purposes. A low current of 300 μA of the proton beam in spallation target concept via 9Be target was accomplished to model neutron spectrum using 208Pb moderator around the target. The graphite reflector and dual layer collimator were planned to prevent and collimate the neutrons produced from proton interactions. Neutron yield per proton, energy distribution, flux, and dose components in the simulated head phantom were estimated by MCNPX code. The neutron beam quality was investigated by diverse filters thicknesses. The maximum epithermal flux transpired using Fluental, Fe, Li, and Bi filters with thicknesses of 7.4, 3, 0.5, and 4 cm, respectively; as well as the epithermal to thermal neutron flux ratio was 161. Results demonstrated that the induced neutrons from a low energy and low current proton may be effective in tumor therapy using 208Pb moderator with average lethargy and also graphite reflector with low absorption cross section to keep the generated neutrons. Combination of spallation-based BNCT and proton therapy can be especially effective, if a high beam intensity cyclotron becomes available.

NEUTRON CAPTURE THERAPY OF A CEREBELLAR HEMANGIOSARCOMA AFTER SURGICAL AND RADIATION TREATMENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farr, L.E.; Yamamoto, L.Y.

1961-10-01

A patient with a hioghly maliognant vascular sarcoma of the cerebellum was treated hv neutron capture therapy. Almost complete elimination of the neoplasm was attained. Other than the skin, normal tissues about and within the neoplastioc mass did not appear to be adversely affected. An unusual and unexpected bulbar conjunctivitis was observed as a complication. The degree of control attained by this experimental procedure was more positive than that previously attained by surgery or conventional x-ray therapy. This is the first attempt to control an intracranial tumor other than glioblastoma multiforme by this procedure. The patient is noteworthy for themore » extreme retention of carbon dioxiode, 60 milli-equivalents per liter in the blood, apparently resulting from functional disturbances of the respiratory center. (auth)« less

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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

2015-05-01

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

Experiments to increase the parameters of the vacuum insulation tandem accelerator for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Kasatov, D. A.; Kolesnikov, J. A.; Koshkarev, A. M.; Kuznetsov, A. S.; Makarov, A. N.; Sokolova, E. O.; Sorokin, I. N.; Sycheva, T. V.; Taskaev, S. Yu.; Shchudlo, I. M.

2016-12-01

An epithermal neutron source that is based on a vacuum insulation tandem accelerator (VITA) and lithium target was created in the Budker Institute of Nuclear Physics for the development of boron neutron capture therapy (BNCT). A stationary proton beam with 2 MeV energy and 1.6 mA current has been obtained. To carry out BNCT, it is necessary to increase the beam parameters up to 2.3 MeV and 3 mA. Ways to increase the parameters of the proton beam have been proposed and discussed in this paper. The results of the experiments are presented.

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

PubMed

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

2014-06-01

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed

Rasouli, Fatemeh S; Masoudi, S Farhad

2015-02-01

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

Boron Neutron Capture Therapy (BNCT) Dose Calculation using Geometrical Factors Spherical Interface for Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zasneda, Sabriani; Widita, Rena

2010-06-22

Boron Neutron Capture Therapy (BNCT) is a cancer therapy by utilizing thermal neutron to produce alpha particles and lithium nuclei. The superiority of BNCT is that the radiation effects could be limited only for the tumor cells. BNCT radiation dose depends on the distribution of boron in the tumor. Absorbed dose to the cells from the reaction 10B (n, {alpha}) 7Li was calculated near interface medium containing boron and boron-free region. The method considers the contribution of the alpha particle and recoiled lithium particle to the absorbed dose and the variation of Linear Energy Transfer (LET) charged particles energy. Geometricalmore » factor data of boron distribution for the spherical surface is used to calculate the energy absorbed in the tumor cells, brain and scalp for case Glioblastoma Multiforme. The result shows that the optimal dose in tumor is obtained for boron concentrations of 22.1 mg {sup 10}B/g blood.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

A. Monti Hughes; ECC Pozzi; S. Thorp

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Bikramjeet; Singh, Paviter; Kumar, Akshay, E-mail: akshaykumar.tiet@gmail.com

2015-05-15

Nanostructured Boron Nitride (BN) has been successfully synthesized by carbo-thermic reduction of Boric Acid (H{sub 3}BO{sub 3}). This method is a relatively low temperature synthesis route and it can be used for large scale production of nanostructured BN. The synthesized nanoparticles have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and differential thermal analyzer (DTA). XRD analysis confirmed the formation of single phase nanostructured Boron Nitride. SEM analysis showed that the particles are spherical in shape. DTA analysis showed that the phase is stable upto 900 °C and the material can be used for high temperature applications asmore » well boron neutron capture therapy (BNCT)« less

Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

PubMed

Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Fukase, Naomasa; Takeuchi, Tamotsu; Sonobe, Hiroshi; Inoue, Masayoshi; Hirose, Tkanori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Kawamoto, Teruya; Fukumori, Yoshinobu; Yamamoto, Satomi; Atagi, Shinji; Sakurai, Yoshinori; Kurosaka, Masahiro; Ono, Koji; Ichikawa, Hideki; Suzuki, Minoru

2015-12-01

Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

System and method for delivery of neutron beams for medical therapy

DOEpatents

Nigg, David W.; Wemple, Charles A.

1999-01-01

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

System and method for delivery of neutron beams for medical therapy

DOEpatents

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

1999-07-06

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

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

PubMed

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

2014-12-01

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

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

NASA Astrophysics Data System (ADS)

Burlon, Alejandro A.; Girola, Santiago; Valda, Alejandro A.; Minsky, Daniel M.; Kreiner, Andrés J.

2010-08-01

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

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

NASA Astrophysics Data System (ADS)

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

2015-07-01

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

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

PubMed

Hashimoto, Y; Hiraga, F; Kiyanagi, Y

2015-12-01

We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical trials for treating recurrent head and neck cancer with boron neutron capture therapy using the Tsing-Hua Open Pool Reactor.

PubMed

Wang, Ling-Wei; Liu, Yen-Wan Hsueh; Chou, Fong-In; Jiang, Shiang-Huei

2018-06-19

Head and neck (HN) cancer is an endemic disease in Taiwan, China. Locally recurrent HN cancer after full-dose irradiation poses a therapeutic challenge, and boron neutron capture therapy (BNCT) may be a solution that could provide durable local control with tolerable toxicity. The Tsing-Hua Open Pool Reactor (THOR) at National Tsing-Hua University in Hsin-Chu, provides a high-quality epithermal neutron source for basic and clinical BNCT research. Our first clinical trial, entitled "A phase I/II trial of boron neutron capture therapy for recurrent head and neck cancer at THOR", was carried out between 2010 and 2013. A total of 17 patients with 23 recurrent HN tumors who had received high-dose photon irradiation were enrolled in the study. The fructose complex of L-boronophenylalanine was used as a boron carrier, and a two-fraction BNCT treatment regimen at 28-day intervals was used for each patient. Toxicity was acceptable, and although the response rate was high (12/17), re-recurrence within or near the radiation site was common. To obtain better local control, another clinical trial entitled "A phase I/II trial of boron neutron capture therapy combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for locally recurrent HN cancer" was initiated in 2014. The first administration of BNCT was performed according to our previous protocol, and IG-IMRT was initiated 28 days after BNCT. As of May 2017, seven patients have been treated with this combination. The treatment-related toxicity was similar to that previously observed with two BNCT applications. Three patients had a complete response, but locoregional recurrence was the major cause of failure despite initially good responses. Future clinical trials combining BNCT with other local or systemic treatments will be carried out for recurrent HN cancer patients at THOR.

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

PubMed

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

2016-09-21

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

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

PubMed

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

2006-12-11

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

Boron neutron capture therapy (BNCT) in Finland: technological and physical prospects after 20 years of experiences.

PubMed

Savolainen, Sauli; Kortesniemi, Mika; Timonen, Marjut; Reijonen, Vappu; Kuusela, Linda; Uusi-Simola, Jouni; Salli, Eero; Koivunoro, Hanna; Seppälä, Tiina; Lönnroth, Nadja; Välimäki, Petteri; Hyvönen, Heini; Kotiluoto, Petri; Serén, Tom; Kuronen, Antti; Heikkinen, Sami; Kosunen, Antti; Auterinen, Iiro

2013-05-01

Boron Neutron Capture Therapy (BNCT) is a binary radiotherapy method developed to treat patients with certain malignant tumours. To date, over 300 treatments have been carried out at the Finnish BNCT facility in various on-going and past clinical trials. In this technical review, we discuss our research work in the field of medical physics to form the groundwork for the Finnish BNCT patient treatments, as well as the possibilities to further develop and optimize the method in the future. Accordingly, the following aspects are described: neutron sources, beam dosimetry, treatment planning, boron imaging and determination, and finally the possibilities to detect the efficacy and effects of BNCT on patients. Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jandel, M.; Bredeweg, T. A.; Fowler, M. M.

2009-01-28

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jandel, Marian

2008-01-01

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

Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy

PubMed Central

Sun, Ting; Li, Yanyan; Huang, Yulun; Zhang, Zizhu; Yang, Weilian; Du, Ziwei; Zhou, Youxin

2016-01-01

The uptake of (10)boron by tumor cells plays an important role for cell damage in boron neutron capture therapy (BNCT). CD133 is frequently expressed in the membrane of glioma stem cells (GSCs), resistant to radiotherapy and chemotherapy, and represents a potential therapeutic target. To increase (10)boron uptake in GSCs, we created a polyamido amine dendrimer, conjugated CD133 monoclonal antibodies, encapsulating mercaptoundecahydrododecaborate (BSH) in void spaces, and monitored the uptake of the bioconjugate nanoparticles by GSCs in vitro and in vivo. Fluorescence microscopy showed the specific uptake of the bioconjugate nanoparticles by CD133-positive GSCs. Treatment with the biconjugate nanoparticles resulted in a significant lethal effect after neutron radiation due to efficient and CD133-independent cellular targeting and uptake in CD133-expressing GSCs. A significantly longer survival occurred in combination with the biconjugate nanoparticles and BSH compared with BSH alone in human intracranial GBM models employing CD133-positive GSCs xenografts. Our data demonstrated that this bioconjugate nanoparticle targets human CD133-positive GSCs and is a potential boron agent in BNCT. PMID:27191269

Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy.

PubMed

Sun, Ting; Li, Yanyan; Huang, Yulun; Zhang, Zizhu; Yang, Weilian; Du, Ziwei; Zhou, Youxin

2016-07-12

The uptake of (10)boron by tumor cells plays an important role for cell damage in boron neutron capture therapy (BNCT). CD133 is frequently expressed in the membrane of glioma stem cells (GSCs), resistant to radiotherapy and chemotherapy, and represents a potential therapeutic target. To increase (10)boron uptake in GSCs, we created a polyamido amine dendrimer, conjugated CD133 monoclonal antibodies, encapsulating mercaptoundecahydrododecaborate (BSH) in void spaces, and monitored the uptake of the bioconjugate nanoparticles by GSCs in vitro and in vivo. Fluorescence microscopy showed the specific uptake of the bioconjugate nanoparticles by CD133-positive GSCs. Treatment with the biconjugate nanoparticles resulted in a significant lethal effect after neutron radiation due to efficient and CD133-independent cellular targeting and uptake in CD133-expressing GSCs. A significantly longer survival occurred in combination with the biconjugate nanoparticles and BSH compared with BSH alone in human intracranial GBM models employing CD133-positive GSCs xenografts. Our data demonstrated that this bioconjugate nanoparticle targets human CD133-positive GSCs and is a potential boron agent in BNCT.

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

PubMed Central

2013-01-01

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

Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study.

PubMed

Kang, Weirong; Svirskis, Darren; Sarojini, Vijayalekshmi; McGregor, Ailsa L; Bevitt, Joseph; Wu, Zimei

2017-05-30

The efficacy of boron neutron capture therapy depends on the selective delivery of 10B to the target. Integrins αvβ3 are transmembrane receptors over-expressed in both glioblastoma cells and its neovasculature. In this study, a novel approach to dual-target glioblastoma vasculature and tumor cells was investigated. Liposomes (124 nm) were conjugated with a αvβ3 ligand, cyclic arginine-glycine-aspartic acid-tyrosine-cysteine peptide (c(RGDyC)-LP) (1% molar ratio) through thiol-maleimide coupling. Expression of αvβ3 in glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC), representing tumor angiogenesis, was determined using Western Blotting with other cells as references. The results showed that both U87 and HUVEC had stronger expression of αvβ3 than other cell types, and the degree of cellular uptake of c(RGDyC)-LP correlated with the αvβ3-expression levels of the cells. In contrast, control liposomes without c(RGDyC) showed little cellular uptake, regardless of cell type. In an in vitro boron neutron capture therapy study, the c(RGDyC)-LP containing sodium borocaptate generated more rapid and significant lethal effects to both U87 and HUVEC than the control liposomes and drug solution. Interestingly, neutron irradiated U87 and HUVEC showed different types of subsequent cell death. In conclusion, this study has demonstrated the potential of a new dual-targeting strategy using c(RGDyC)-LP to improve boron neutron capture therapy for glioblastoma.

Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study

PubMed Central

Kang, Weirong; Svirskis, Darren; Sarojini, Vijayalekshmi; McGregor, Ailsa L.; Bevitt, Joseph; Wu, Zimei

2017-01-01

The efficacy of boron neutron capture therapy depends on the selective delivery of 10B to the target. Integrins αvβ3 are transmembrane receptors over-expressed in both glioblastoma cells and its neovasculature. In this study, a novel approach to dual-target glioblastoma vasculature and tumor cells was investigated. Liposomes (124 nm) were conjugated with a αvβ3 ligand, cyclic arginine-glycine-aspartic acid-tyrosine-cysteine peptide (c(RGDyC)-LP) (1% molar ratio) through thiol-maleimide coupling. Expression of αvβ3 in glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC), representing tumor angiogenesis, was determined using Western Blotting with other cells as references. The results showed that both U87 and HUVEC had stronger expression of αvβ3 than other cell types, and the degree of cellular uptake of c(RGDyC)-LP correlated with the αvβ3-expression levels of the cells. In contrast, control liposomes without c(RGDyC) showed little cellular uptake, regardless of cell type. In an in vitro boron neutron capture therapy study, the c(RGDyC)-LP containing sodium borocaptate generated more rapid and significant lethal effects to both U87 and HUVEC than the control liposomes and drug solution. Interestingly, neutron irradiated U87 and HUVEC showed different types of subsequent cell death. In conclusion, this study has demonstrated the potential of a new dual-targeting strategy using c(RGDyC)-LP to improve boron neutron capture therapy for glioblastoma. PMID:28402271

Apoptosis through Bcl-2/Bax and Cleaved Caspase Up-Regulation in Melanoma Treated by Boron Neutron Capture Therapy

PubMed Central

Faião-Flores, Fernanda; Coelho, Paulo Rogério Pinto; Toledo Arruda-Neto, João Dias; Maria-Engler, Silvya Stuchi; Tiago, Manoela; Capelozzi, Vera Luiza; Giorgi, Ricardo Rodrigues; Maria, Durvanei Augusto

2013-01-01

Boron neutron capture therapy (BNCT) is a binary treatment involving selective accumulation of boron carriers in a tumor followed by irradiation with a thermal or epithermal neutron beam. The neutron capture reaction with a boron-10 nucleus yields high linear energy transfer (LET) particles, alpha and 7Li, with a range of 5 to 9 µm. These particles can only travel very short distances and release their damaging energy directly into the cells containing the boron compound. We aimed to evaluate proliferation, apoptosis and extracellular matrix (ECM) modifications of B16F10 melanoma and normal human melanocytes after BNCT. The amounts of soluble collagen and Hsp47, indicating collagen synthesis in the ECM, as well as the cellular markers of apoptosis, were investigated. BNCT decreased proliferation, altered the ECM by decreasing collagen synthesis and induced apoptosis by regulating Bcl-2/Bax in melanoma. Additionally, BNCT also increased the levels of TNF receptor and the cleaved caspases 3, 7, 8 and 9 in melanoma. These results suggest that multiple pathways related to cell death and cell cycle arrest are involved in the treatment of melanoma by BNCT. PMID:23527236

Are gadolinium contrast agents suitable for gadolinium neutron capture therapy?

PubMed

De Stasio, Gelsomina; Rajesh, Deepika; Casalbore, Patrizia; Daniels, Matthew J; Erhardt, Robert J; Frazer, Bradley H; Wiese, Lisa M; Richter, Katherine L; Sonderegger, Brandon R; Gilbert, Benjamin; Schaub, Sebastien; Cannara, Rachel J; Crawford, John F; Gilles, Mary K; Tyliszczak, Tolek; Fowler, John F; Larocca, Luigi M; Howard, Steven P; Mercanti, Delio; Mehta, Minesh P; Pallini, Roberto

2005-06-01

Gadolinium neutron capture therapy (GdNCT) is a potential treatment for malignant tumors based on two steps: (1) injection of a tumor-specific (157)Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction can induce cell death provided that Gd is proximate to DNA. Here, we studied the nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two Gd compounds commonly used for magnetic resonance imaging, to evaluate their potential as GdNCT agents. Using synchrotron X-ray spectromicroscopy, we analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM cells exposed to Gd-DTPA or Gd-DOTA for 0-72 hours; (2) intracerebrally implanted C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor samples from GBM patients injected with Gd-DTPA. In cell cultures, Gd-DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after single and double injection of Gd-DOTA, respectively. In contrast, in human GBM tumors 6.1% of the cell nuclei contained Gd-DTPA. Efficacy of Gd-DTPA and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient number of tumor cell nuclei incorporating Gd. Although multiple administration schedules in vivo might induce Gd penetration into more tumor cell nuclei, a search for new Gd compounds with higher nuclear affinity is warranted before planning GdNCT in animal models or clinical trials.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

2007-10-01

Purpose: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. Methods and Materials: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria andmore » 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.« less

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

PubMed

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

2013-08-06

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.

Therapeutic efficacy for hepatocellular carcinoma by boric acid-mediated boron neutron capture therapy in a rat model.

PubMed

Lin, Sy-Yu; Lin, Chen-Jou; Liao, Jiunn-Wang; Peir, Jinn-Jer; Chen, Wei-Lin; Chi, Chin-Wen; Lin, Yung-Chang; Liu, Yu-Ming; Chou, Fong-In

2013-11-01

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Boron neutron capture therapy (BNCT) may provide an alternative therapy for HCC. This study investigated the therapeutic efficacy of boric acid (BA)-mediated BNCT for HCC in a rat model. The pharmacokinetic and biodistribution of BA in N1S1 tumor-bearing rats were analyzed. Rats were injected with 25 mg B/kg body weight via tail veins before neutron irradiation at the Tsing Hua Open-pool Reactor, and the efficacy of BNCT was evaluated from the tumor size, tumor blood flow, and biochemical analyses. HCC-bearing rats administered BNCT showed reductions in tumor size on ultrasound imaging, as well as an obvious reduction in the distribution of tumor blood flow. The lesion located in livers had disappeared on the 80th day after BNCT; a recovery of values to normal levels was also recorded. BA-mediated BNCT is a promising alternative for liver cancer therapy since the present study demonstrated the feasibility of curing a liver tumor and restoring liver function in rats. Efforts are underway to investigate the histopathological features and the detailed mechanisms of BA-mediated BNCT.

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

NASA Astrophysics Data System (ADS)

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.

Optimization of Boron Neutron Capture Therapy for the Treatment of Undifferentiated Thyroid Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dagrosa, Maria Alejandra; Thomasz, Lisa M.Sc.; Longhino, Juan

Purpose: To analyze the possible increase in efficacy of boron neutron capture therapy (BNCT) for undifferentiated thyroid carcinoma (UTC) by using p-boronophenylalanine (BPA) plus 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX (BOPP) and BPA plus nicotinamide (NA) as a radiosensitizer of the BNCT reaction. Methods and Materials: Nude mice were transplanted with a human UTC cell line (ARO), and after 15 days they were treated as follows: (1) control, (2) NCT (neutrons alone), (3) NCT plus NA (100 mg/kg body weight [bw]/day for 3 days), (4) BPA (350 mg/kg bw) + neutrons, (5) BPA + NA + neutrons, and (6) BPA + BOPP (60more » mg/kg bw) + neutrons. The flux of the mixed (thermal + epithermal) neutron beam was 2.8 x 10{sup 8} n/cm{sup 2}/sec for 83.4 min. Results: Neutrons alone or with NA caused some tumor growth delay, whereas in the BPA, BPA + NA, and BPA + BOPP groups a 100% halt of tumor growth was observed in all mice at 26 days after irradiation. When the initial tumor volume was 50 mm{sup 3} or less, complete remission was found with BPA + NA (2 of 2 mice), BPA (1 of 4), and BPA + BOPP (7 of 7). After 90 days of complete regression, recurrence of the tumor was observed in BPA + NA (2 of 2) and BPA + BOPP (1 of 7). The determination of apoptosis in tumor samples by measurements of caspase-3 activity showed an increase in the BNCT (BPA + NA) group at 24 h (p < 0.05 vs. controls) and after the first week after irradiation in the three BNCT groups. Terminal transferase dUTP nick end labeling analysis confirmed these results. Conclusions: Although NA combined with BPA showed an increase of apoptosis at early times, only the group irradiated after the combined administration of BPA and BOPP showed a significantly improved therapeutic response.« less

Radiobiological response of U251MG, CHO-K1 and V79 cell lines to accelerator-based boron neutron capture therapy

PubMed Central

Sato, Eisuke; Zaboronok, Alexander; Yamamoto, Tetsuya; Nakai, Kei; Taskaev, Sergey; Volkova, Olga; Mechetina, Ludmila; Taranin, Alexander; Kanygin, Vladimir; Isobe, Tomonori; Mathis, Bryan J; Matsumura, Akira

2018-01-01

Abstract In the current article, we provide in vitro efficacy evaluation of a unique accelerator-based neutron source, constructed at the Budker Institute of Nuclear Physics (Novosibirsk, Russian Federation), for boron neutron capture therapy (BNCT), which is particularly effective in the case of invasive cancers. U251MG, CHO-K1 and V79 cells were incubated and irradiated in various concentrations of boric acid with epithermal neutrons for 2–3 h in a plexiglass phantom, using 2.0 MeV proton energy and 1.5–3.0 mA proton current, resulting in a neutron fluence of 2.16 × 1012 cm−2. The survival curves of cells loaded with boron were normalized to those irradiated without boron (to exclude the influence of the fast neutron and gamma dose components) and fit to the linear–quadratic (LQ) model. Colony formation assays showed the following cell survival rates (means ± SDs): CHO-K1: 0.348 ± 0.069 (10 ppm), 0.058 ± 0.017 (20 ppm), 0.018 ± 0.005 (40 ppm); V79: 0.476 ± 0.160 (10 ppm), 0.346 ± 0.053 (20 ppm), 0.078 ± 0.015 (40 ppm); and U251MG: 0.311 ± 0.061 (10 ppm), 0.131 ± 0.022 (20 ppm), 0.020 ± 0.010 (40 ppm). The difference between treated cells and controls was significant in all cases (P < 0.01) and confirmed that the neutron source and irradiation regimen were sufficient for control over cell colony formation. We believe our study will serve as a model for ongoing in vitro experiments on neutron capture therapy to advance in this area for further development of accelerator-based BNCT into the clinical phase. PMID:29281044

Neutron capture cross sections of Kr

NASA Astrophysics Data System (ADS)

Fiebiger, Stefan; Baramsai, Bayarbadrakh; Couture, Aaron; Krtička, Milan; Mosby, Shea; Reifarth, René; O'Donnell, John; Rusev, Gencho; Ullmann, John; Weigand, Mario; Wolf, Clemens

2018-01-01

Neutron capture and β- -decay are competing branches of the s-process nucleosynthesis path at 85Kr [1], which makes it an important branching point. The knowledge of its neutron capture cross section is therefore essential to constrain stellar models of nucleosynthesis. Despite its importance for different fields, no direct measurement of the cross section of 85Kr in the keV-regime has been performed. The currently reported uncertainties are still in the order of 50% [2, 3]. Neutron capture cross section measurements on a 4% enriched 85Kr gas enclosed in a stainless steel cylinder were performed at Los Alamos National Laboratory (LANL) using the Detector for Advanced Neutron Capture Experiments (DANCE). 85Kr is radioactive isotope with a half life of 10.8 years. As this was a low-enrichment sample, the main contaminants, the stable krypton isotopes 83Kr and 86Kr, were also investigated. The material was highly enriched and contained in pressurized stainless steel spheres.

SU-E-T-21: A D-D Based Neutron Generator System for Boron Neutron Capture Therapy: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsieh, M; Liu, Y; Nie, L

2015-06-15

Purpose: To investigate the feasibility of a deuterium-deuterium (DD) neutron generator for application in boron neutron capture therapy (BNCT) of brain cancer Methods: MCNP simulations were performed using a head phantom and a monoenergetic neutron source, which resembles the point source in a DD generator that emits 2.45-MeV neutrons. Source energies ranging from 5eV to 2.45MeV were simulated to determine the optimal treatment energy. The phantom consisted of soft tissue, brain tissue, skull, skin layer, and a brain tumor of 5 cm in diameter. Tumor depth was varied from 5–10 cm. Boron-10 concentrations of 10 ppm, 15 ppm, and 30more » ppm were used in the soft/brain tissues, skin, and tumor, respectively. The neutron flux required to deliver 60 Gy to the tumor as well as the normal tissue doses were determined. Results: Beam energies between 5eV and 10keV obtained doses with the highest dose ratios (3.3–25.9) between the tumor and the brain at various depths. The dose ratio with 2.45-MeV neutrons ranged from 0.8–6.6. To achieve the desired tumor dose in 40 minutes, the required neutron flux for a DD generator was between 8.8E10 and 5.2E11 n/s and the resulting brain dose was between 2.3 and 18 Gy, depending on the tumor depth. The skin and soft tissue doses were within acceptable tolerances. The boron-neutron interaction accounted for 54–58% of the total dose. Conclusion: This study shows that the DD neutron generator can be a feasible neutron source for BNCT. The required neutron flux for treatment is achievable with the current DD neutron technology. With a well-designed beam shaping assembly and treatment geometry, the neutron flux can be further improved and a 60-Gy prescription can be accurately delivered to the target while maintaining tolerable normal tissue doses. Further experimental studies will be developed and conducted to validate the simulation results.« less

Neutron Capture Gamma-Ray Libraries for Nuclear Applications

NASA Astrophysics Data System (ADS)

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

2011-06-01

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

Neutron capture cross section of ^243Am

NASA Astrophysics Data System (ADS)

Jandel, M.

2009-10-01

The Detector for Advanced Neutron Capture Experiments (DANCE) at Los Alamos National Laboratory (LANL) was used for neutron capture cross section measurement on ^243Am. The high granularity of DANCE (160 BaF2 detectors in a 4π geometry) enables the efficient detection of prompt gamma-rays following neutron capture. DANCE is located on the 20.26 m neutron flight path 14 (FP14) at the Manuel Lujan Jr. Neutron Scattering Center at the Los Alamos Neutron Science Center (LANSCE). The methods and techniques established in [1] were used for the determination of the ^243Am neutron capture cross section. The cross sections were obtained in the range of neutron energies from 0.02 eV to 400 keV. The resonance region was analyzed using SAMMY7 and resonance parameters were extracted. The results will be compared to existing evaluations and calculations. Work was performed under the auspices of the U.S. Department of Energy at Los Alamos National Laboratory by the Los Alamos National Security, LLC under Contract No. DE-AC52-06NA25396 and at Lawrence Livermore National Laboratory by the Lawrence Livermore National Security, LLC under Contract No. DE-AC52-07NA27344. [4pt] [1] M. Jandel et al., Phys. Rev. C78, 034609 (2008)

Opportunities afforded by the intense nanosecond neutron pulses from a plasma focus source for neutron capture therapy and the preliminary simulation results

NASA Astrophysics Data System (ADS)

Giannini, G.; Gribkov, V.; Longo, F.; Ramos Aruca, M.; Tuniz, C.

2012-11-01

The use of short and powerful neutron pulses for boron neutron capture therapy (BNCT) can potentially increase selectivity and reduce the total dose absorbed by the patient. The biological effects of radiation depend on the dose, the dose power and the spatial distribution of the microscopic energy deposition. A dense plasma focus (DPF) device emits very short (in the nanosecond range) and extremely intense pulses of fast neutrons (2.5 or 14 MeV neutrons—from D-D or D-T nuclear reactions) and x-rays. Optimal spectra of neutrons formed for use in BNCT must contain an epithermal part to ensure a reasonable penetration depth into tissues at high enough cross-section on boron. So the powerful nanosecond pulses of fast neutrons generated by DPF must be moderated. After this moderation, the pulse duration must be shorter compared with the duration of the reaction with free radicals, that is, ⩾1 μs. In this work we focus on the development of a detailed simulation of interaction of short-pulse radiation from a DPF with the device's materials and with different types of moderators to estimate the dose power at the cells for this dynamic case. The simulation was carried out by means of the Geant4 toolkit in two main steps: the modeling of the pulsed neutron source device itself; the study of the interaction of fast mono-energetic neutrons with a moderator specific for BNCT.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, C.K.C.; Sutton, M.; Evans, T.M.

1999-01-01

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

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

PubMed Central

2013-01-01

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

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

PubMed

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

2011-12-01

Within the frame of an ongoing project to develop a folded Tandem-Electrostatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT), we discuss here the electrostatic design of the machine, including the accelerator tubes with electrostatic quadrupoles and the simulations for the transport and acceleration of a high intensity beam. Copyright © 2011 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model.

PubMed

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

2012-08-01

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT, boronophenylalanine (BPA) + neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA-BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks post-treatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA-BNCT, 2.7 ± 1.8 for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mg fell significantly to 19 ± 16 mg for BPA-BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA-BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA-BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.

Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model

DOE Office of Scientific and Technical Information (OSTI.GOV)

David W. Nigg

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA–BNCT, boronophenylalanine (BPA) ? neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA–BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks posttreatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA–BNCT, 2.7 ± 1.8more » for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mgfell significantly to 19 ± 16 mg for BPA–BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA–BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA– BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.« less

The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide.

PubMed

Michiue, Hiroyuki; Sakurai, Yoshinori; Kondo, Natsuko; Kitamatsu, Mizuki; Bin, Feng; Nakajima, Kiichiro; Hirota, Yuki; Kawabata, Shinji; Nishiki, Tei-ichi; Ohmori, Iori; Tomizawa, Kazuhito; Miyatake, Shin-ichi; Ono, Koji; Matsui, Hideki

2014-03-01

New anti-cancer therapy with boron neutron capture therapy (BNCT) is based on the nuclear reaction of boron-10 with neutron irradiation. The median survival of BNCT patients with glioblastoma was almost twice as long as those receiving standard therapy in a Japanese BNCT clinical trial. In this clinical trial, two boron compounds, BPA (boronophenylalanine) and BSH (sodium borocaptate), were used for BNCT. BPA is taken up into cells through amino acid transporters that are expressed highly in almost all malignant cells, but BSH cannot pass through the cell membrane and remains outside the cell. We simulated the energy transfer against the nucleus at different locations of boron from outside the cell to the nuclear region with neutron irradiation and concluded that there was a marked difference between inside and outside the cell in boron localization. To overcome this disadvantage of BSH in BNCT, we used a cell-penetrating peptide system for transduction of BSH. CPP (cell-membrane penetrating peptide) is very common peptide domains that transduce many physiologically active substances into cells in vitro and in vivo. BSH-fused CPPs can penetrate the cell membrane and localize inside a cell. To increase the boron ratio in one BSH-peptide molecule, 8BSH fused to 11R with a dendritic lysine structure was synthesized and administrated to malignant glioma cells and a brain tumor mouse model. 8BSH-11R localized at the cell nucleus and showed a very high boron value in ICP results. With neutron irradiation, the 8BSH-11R administrated group showed a significant cancer killing effect compared to the 100 times higher concentration of BSH-administrated group. We concluded that BSH-fused CPPs were one of the most improved and potential boron compounds in the next-stage BNCT trial and 8BSH-11R may be applied in the clinical setting. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preliminary dosimetric study on feasibility of multi-beam boron neutron capture therapy in patients with diffuse intrinsic pontine glioma without craniotomy.

PubMed

Lee, Jia-Cheng; Chuang, Keh-Shih; Chen, Yi-Wei; Hsu, Fang-Yuh; Chou, Fong-In; Yen, Sang-Hue; Wu, Yuan-Hung

2017-01-01

Diffuse intrinsic pontine glioma is a very frustrating disease. Since the tumor infiltrates the brain stem, surgical removal is often impossible. For conventional radiotherapy, the dose constraint of the brain stem impedes attempts at further dose escalation. Boron neutron capture therapy (BNCT), a targeted radiotherapy, carries the potential to selectively irradiate tumors with an adequate dose while sparing adjacent normal tissue. In this study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of BNCT. NCTPlan Ver. 1.1.44 was used for dose calculations. Compared with two and three fields, the average maximal dose to the normal brain may be lowered to 7.35 ± 0.72 Gy-Eq by four-field irradiation. The mean ratio of minimal dose to clinical target volume and maximal dose to normal tissue was 2.41 ± 0.26 by four-field irradiation. A therapeutic benefit may be expected with multi-field boron neutron capture therapy to treat diffuse intrinsic pontine glioma without craniotomy, while the maximal dose to the normal brain would be minimized by using the four-field setting.

Preliminary dosimetric study on feasibility of multi-beam boron neutron capture therapy in patients with diffuse intrinsic pontine glioma without craniotomy

PubMed Central

Lee, Jia-Cheng; Chuang, Keh-Shih; Chen, Yi-Wei; Hsu, Fang-Yuh; Chou, Fong-In; Yen, Sang-Hue

2017-01-01

Diffuse intrinsic pontine glioma is a very frustrating disease. Since the tumor infiltrates the brain stem, surgical removal is often impossible. For conventional radiotherapy, the dose constraint of the brain stem impedes attempts at further dose escalation. Boron neutron capture therapy (BNCT), a targeted radiotherapy, carries the potential to selectively irradiate tumors with an adequate dose while sparing adjacent normal tissue. In this study, 12 consecutive patients treated with conventional radiotherapy in our institute were reviewed to evaluate the feasibility of BNCT. NCTPlan Ver. 1.1.44 was used for dose calculations. Compared with two and three fields, the average maximal dose to the normal brain may be lowered to 7.35 ± 0.72 Gy-Eq by four-field irradiation. The mean ratio of minimal dose to clinical target volume and maximal dose to normal tissue was 2.41 ± 0.26 by four-field irradiation. A therapeutic benefit may be expected with multi-field boron neutron capture therapy to treat diffuse intrinsic pontine glioma without craniotomy, while the maximal dose to the normal brain would be minimized by using the four-field setting. PMID:28662135

Hybrid Calcium Phosphate-Polymeric Micelles Incorporating Gadolinium Chelates for Imaging-Guided Gadolinium Neutron Capture Tumor Therapy.

PubMed

Mi, Peng; Dewi, Novriana; Yanagie, Hironobu; Kokuryo, Daisuke; Suzuki, Minoru; Sakurai, Yoshinori; Li, Yanmin; Aoki, Ichio; Ono, Koji; Takahashi, Hiroyuki; Cabral, Horacio; Nishiyama, Nobuhiro; Kataoka, Kazunori

2015-06-23

Gadolinium (Gd) chelates-loaded nanocarriers have high potential for achieving magnetic resonance imaging (MRI)-guided Gd neutron capture therapy (GdNCT) of tumors. Herein, we developed calcium phosphate micelles hybridized with PEG-polyanion block copolymers, and incorporated with the clinical MRI contrast agent Gd-diethylenetriaminepentaacetic acid (Gd-DTPA/CaP). The Gd-DTPA/CaP were nontoxic to cancer cells at the concentration of 100 μM based on Gd-DTPA, while over 50% of the cancer cells were killed by thermal neutron irradiation at this concentration. Moreover, the Gd-DTPA/CaP showed a dramatically increased accumulation of Gd-DTPA in tumors, leading to the selective contrast enhancement of tumor tissues for precise tumor location by MRI. The enhanced tumor-to-blood distribution ratio of Gd-DTPA/CaP resulted in the effective suppression of tumor growth without loss of body weight, indicating the potential of Gd-DTPA/CaP for safe cancer treatment.

Influence of p53 status on the effects of boron neutron capture therapy in glioblastoma.

PubMed

Seki, Keiko; Kinashi, Yuko; Takahashi, Sentaro

2015-01-01

The tumor suppressor gene p53 is mutated in glioblastoma. We studied the relationship between the p53 gene and the biological effects of boron neutron capture therapy (BNCT). The human glioblastoma cells; A172, expressing wild-type p53, and T98G, with mutant p53, were irradiated by the Kyoto University Research Reactor (KUR). The biological effects after neutron irradiation were evaluated by the cell killing effect, 53BP1 foci assay and apoptosis induction. The survival-fraction data revealed that A172 was more radiosensitive than T98G, but the difference was reduced when boronophenylalanine (BPA) was present. Both cell lines exhibited similar numbers of foci, suggesting that the initial levels of DNA damage did not depend on p53 function. Detection of apoptosis revealed a lower rate of apoptosis in the T98G. BNCT causes cell death in glioblastoma cells, regardless of p53 mutation status. In T98G cells, cell killing and apoptosis occurred effectively following BNCT. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Influence of Neutron Sources and 10B Concentration on Boron Neutron Capture Therapy for Shallow and Deeper Non-small Cell Lung Cancer.

PubMed

Yu, Haiyan; Tang, Xiaobin; Shu, Diyun; Liu, Yuanhao; Geng, Changran; Gong, Chunhui; Hang, Shuang; Chen, Da

2017-03-01

Boron Neutron Capture Therapy (BNCT) is a radiotherapy that combines biological targeting and high Linear Energy Transfer (LET). It is considered a potential therapeutic approach for non-small cell lung cancer (NSCLC). It could avoid the inaccurate treatment caused by the lung motion during radiotherapy, because the dose deposition mainly depends on the boron localization and neutron source. Thus, B concentration and neutron sources are both principal factors of BNCT, and they play significant roles in the curative effect of BNCT for different cases. The purpose was to explore the feasibility of BNCT treatment for NSCLC with either of two neutron sources (the epithermal reactor at the Massachusetts Institute of Technology named "MIT source" and the accelerator neutron source designed in Argentina named "MEC source") and various boron concentrations. Shallow and deeper lung tumors were defined in the Chinese hybrid radiation phantom, and the Monte Carlo method was used to calculate the dose to tumors and healthy organs. The MEC source was more appropriate to treat the shallow tumor (depth of 6 cm) with a shorter treatment time. However, the MIT source was more suitable for deep lung tumor (depth of 9 cm) treatment, as the MEC source is more likely to exceed the skin dose limit. Thus, a neutron source consisting of more fast neutrons is not necessarily suitable for deep treatment of lung tumors. Theoretical distribution of B in tumors and organs at risk (especially skin) was obtained to meet the treatable requirement of BNCT, which may provide the references to identify the feasibility of BNCT for the treatment of lung cancer using these two neutron sources in future clinical applications.

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

PubMed

Nizioł, Joanna; Uram, Łukasz; Szuster, Magdalena; Sekuła, Justyna; Ruman, Tomasz

2015-10-01

Boron-neutron capture therapy (BNCT) is a binary anticancer therapy that requires boron compound for nuclear reaction during which high energy alpha particles and lithium nuclei are formed. Unnatural, boron-containing nucleoside with hydrophobic pinacol moiety was investigated as a potential BNCT boron delivery agent. Biological properties of this compound are presented for the first time and prove that boron nucleoside has low cytotoxicity and that observed apoptotic effects suggest alteration of important functions of cancer cells. Mass spectrometry analysis of DNA from cancer cells proved that boron nucleoside is inserted into nucleic acids as a functional nucleotide derivative. NMR studies present very high degree of similarity of natural dG-dC base pair with dG-boron nucleoside system. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-06-01

The purpose of this study was to clarify the correlation between the radiation dose and histopathological findings in patients with glioblastoma multiforme (GBM) treated with boron neutron capture therapy (BNCT). Histopathological studies were performed on specimens from 8 patients, 3 had undergone salvage surgery and 5 were autopsied. For histopathological cure of GBM at the primary site, the optimal minimal dose to the gross tumor volume (GTV) and the clinical target volume (CTV) were 68Gy(w) and 44Gy(w), respectively. Copyright © 2014. Published by Elsevier Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallace, Christine

2001-05-29

Assessment of research records of Boron Neutron Capture Therapy was conducted at Brookhaven National Laboratory and Beth Israel Deaconess Medical Center using the Code of Federal Regulations, FDA Regulations and Good Clinical Practice Guidelines. Clinical data were collected from subjects' research charts, and differences in conduct of studies at both centers were examined. Records maintained at Brookhaven National Laboratory were not in compliance with regulatory standards. Beth Israel's records followed federal regulations. Deficiencies discovered at both sites are discussed in the reports.

The Perspectives of the Boron Neutron Capture Therapy-Clinical Applications Research and Development in Saudi Arabia

NASA Astrophysics Data System (ADS)

Badhrees, I.; Alrumayan, F.; Mahube, F.

Boron Neutron Capture Therapy (BNCT) is a binary form of experimental radiotherapy which is based on the administration of a drug able to concentrate the isotopes in a tumor cell that later are irradiated with a neutron beam. Even though the first evidence of the success of this treatment dates back many years ago, BNCT showed successful treatment results in malignant melanoma, and Glioblastoma. In order for BNCT to be successful, a sufficient amount of Boron (10B) must be selectively delivered to the tumor cell, and then irradiated by neutrons of sufficient enough. The CS-30 cyclotron at King Faisal Specialist Hospital & Research Center is a positive-ion machine capable of accelerating protons at 26MeV, and other isotopes as well. Although the peak beam intensity from the CS-30 is low, the key to success of using it for the BNCT is by using a high average beam current at low energy. This work is aimed at testing the capability of the CS-30 Cyclotron to produce a low-energy neutron beam to be used to activate the Boron atoms injected into the tumor cell, through simulation of a compatible moderator. We are also planning to measure the overall dosimetry of the energy dose as well as that for the boron in the tumor cell.

Thermal-neutron capture for A=26-35

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chunmei, Z.; Firestone, R.B.

2001-06-01

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

Thermal-neutron capture for A=36-44

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chunmei, Z.; Firestone, R.B.

2003-01-01

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

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

PubMed

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

2015-12-01

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

A Simple Correlation for Neutron Capture Rates from Nuclear Masses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Couture, Aaron Joseph

Recent studies of neutron capture performed at LANL have revealed a previously unrecognized connection between nuclear masses and the average neutron capture cross section. A team of three scientists from Los Alamos (P-27), Yale Univ., and Istanbul Univ. (Turkey) recently discovered this connection and have published their results as a Rapid Communication in Physical Review C. Neutron capture is a reaction in which a free neutron is absorbed by the nucleus, keeping the element unchanged, but changing isotopes. This reaction is typically exothermic. As a result, the reaction can proceed even when many other reaction channels are closed. In anmore » astrophysical environment, this means that neutron capture is the primary mechanism by which all of the elements with atomic number greater than nickel are produced is neutron capture.« less

Neutron Capture Experiments Using the DANCE Array at Los Alamos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dashdorj, D.; MonAme Scientific Research Center, Ulaanbaatar; Mitchell, G. E.

2009-03-31

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

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

DOE PAGES

Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.; ...

2017-08-01

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. We implanted mice 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-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.

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. We implanted mice 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-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of 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.« less

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

PubMed Central

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

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.

PubMed

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. 24 Na, 38 Cl, 80m Br, 82 Br, 56 Mn, and 42 K were identified, and their saturated radioactivities were (1.4 ± 0.1) × 10 2 , (2.2 ± 0.1) × 10 1 , (3.4 ± 0.4) × 10 2 , 2.8 ± 0.1, 8.0 ± 0.1, and (3.8 ± 0.1) × 10 1 Bq/g/mA, respectively. The 24 Na 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.

L-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, eithermore » 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an L-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.« less

Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma.

PubMed

Sasai, Masao; Nakamura, Hiroyuki; Sougawa, Nagako; Sakurai, Yoshinori; Suzuki, Minoru; Lee, Chun Man

2016-03-01

Malignant pleural mesothelioma (MPM) is a refractory cancer of the pleura caused by asbestos exposure. MPM is difficult to treat because it easily disseminates. Boron neutron capture therapy (BNCT) is a radiotherapy in which cancer cells that selectively take up (10)Boron-containing compounds are destroyed, and normal cells are uninjured. Hyaluronan (HA) is a ligand of cluster of differentiation 44 (CD44), that is expressed on MPM cells. In order to enhance BNCT for MPM tumors, we developed a novel HA-containing (10)B (sodium borocaptate: BSH) formulation (HA-BND-S). We examined the efficacy of HA-BND-S using MPM cells and a mouse MPM model. HA-BND-S preferentially bound MPM cells dose-dependently, and increased the cytotoxicity of BNCT compared to BSH in vitro. HA-BND-S administration significantly increased the survival of MPM tumor-bearing mice compared to BSH at the same (10)B dosage in BNCT. Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.

Analysis on the emission and potential application of Cherenkov radiation in boron neutron capture therapy: A Monte Carlo simulation study.

PubMed

Shu, Di-Yun; Geng, Chang-Ran; Tang, Xiao-Bin; Gong, Chun-Hui; Shao, Wen-Cheng; Ai, Yao

2018-07-01

This paper was aimed to explore the physics of Cherenkov radiation and its potential application in boron neutron capture therapy (BNCT). The Monte Carlo toolkit Geant4 was used to simulate the interaction between the epithermal neutron beam and the phantom containing boron-10. Results showed that Cherenkov photons can only be generated from secondary charged particles of gamma rays in BNCT, in which the 2.223 MeV prompt gamma rays are the main contributor. The number of Cherenkov photons per unit mass generated in the measurement region decreases linearly with the increase of boron concentration in both water and tissue phantom. The work presented the fundamental basis for applications of Cherenkov radiation in BNCT. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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

2011-12-01

Several ion sources have been developed and an ion source test stand has been mounted for the first stage of a Tandem-Electrostatic-Quadrupole facility For Accelerator-Based Boron Neutron Capture Therapy. A first source, designed, fabricated and tested is a dual chamber, filament driven and magnetically compressed volume plasma proton ion source. A 4 mA beam has been accelerated and transported into the suppressed Faraday cup. Extensive simulations of the sources have been performed using both 2D and 3D self-consistent codes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: comparison of clinical results obtained with BNCT and conventional treatment.

PubMed

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

2014-01-01

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

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

PubMed

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

2005-12-01

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

Neutron capture reactions in astrophysics

NASA Astrophysics Data System (ADS)

Käppeler, F.

1985-01-01

About 2/3 of the chemical elements in nature were formed in neutron capture reactions. During the life of a star there are certain evolutionary stages where neutrons are available to build up the elements beyond iron which cannot be synthesized by charged particle reactions. The observed abundance pattern allows to distinguish a rapid and a slow neutron capture process (r- and s-process). The r-process taking place far from the valley of stability is difficult to investigate because of the required extrapolation of nuclear properties to extreme neutron rich nuclei. The s-process, on the other hand, proceeds along the valley of stability. Therefore, the involved isotopes are accessible to laboratory measurements. This information allows for quantitative calculation of s-process abundances and other parameters which represent constraints for stellar models. Two examples are outlined: (i) the s-process branching at A=147, 148 yields a rather accurate value for the neutron density. (ii) Comparison of s-process abundances with observations of stellar atmospheres are particularly interesting for the unstable isotopes 93Zr, 99Tc and 147Pm. Their deficiency with respect to stable neighbors may yield estimates for the transport time from the stellar interior to the surface.

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

PubMed

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

2015-01-01

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

Trivalent galactosyl-functionalized mesoporous silica nanoparticles as a target-specific delivery system for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Lai, Chian-Hui; Lai, Nien-Chu; Chuang, Yung-Jen; Chou, Fong-In; Yang, Chia-Min; Lin, Chun-Cheng

2013-09-01

A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium borocaptate (BSH), T-Gal-B-Cy3@MSN provides a higher delivery efficiency (over 40-50 fold) of boron atoms and a better effect of BNCT in neutron irradiation experiments. MTT assays show a very low cytotoxicity for T-Gal-B-Cy3@MSN over a 2 h incubation time. The results are promising for the design of multifunctional MSNs as potential BNCT agents for clinical use.A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium

Neutron capture by hook or by crook

NASA Astrophysics Data System (ADS)

Mosby, Shea

2016-03-01

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

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

NASA Astrophysics Data System (ADS)

Santa Cruz, Gustavo A.; González, Sara J.; Dagrosa, Alejandra; Schwint, Amanda E.; Carpano, Marina; Trivillin, Verónica A.; Boggio, Esteban F.; Bertotti, José; Marín, Julio; Monti Hughes, Andrea; Molinari, Ana J.; Albero, Miguel

2011-05-01

Boron Neutron Capture Therapy (BNCT) is a treatment modality, currently focused on the treatment of cancer, which involves a tumor selective 10B compound and a specially tuned neutron beam to produce a lethal nuclear reaction. BNCT kills target cells with microscopic selectivity while sparing normal tissues from potentially lethal doses of radiation. In the context of the Argentine clinical and research BNCT projects at the National Atomic Energy Commission and in a strong collaboration with INVAP SE, we successfully implemented Dynamic Infrared Imaging (DIRI) in the clinical setting for the observation of cutaneous melanoma patients and included DIRI as a non invasive methodology in several research protocols involving small animals. We were able to characterize melanoma lesions in terms of temperature and temperature rate-of-recovery after applying a mild cold thermal stress, distinguishing melanoma from other skin pigmented lesions. We observed a spatial and temporal correlation between skin acute reactions after irradiation, the temperature pattern and the dose distribution. We studied temperature distribution as a function of tumor growth in mouse xenografts, observing a significant correlation between tumor temperature and drug uptake; we investigated temperature evolution in the limbs of Wistar rats for a protocol of induced rheumatoid arthritis (RA), DIRI being especially sensitive to RA induction even before the development of clinical signs and studied surface characteristics of tumors, precancerous and normal tissues in a model of oral cancer in the hamster cheek pouch.

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

PubMed

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

Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy

PubMed Central

Singh, Bikramjeet; Kaur, Gurpreet; Singh, Paviter; Singh, Kulwinder; Kumar, Baban; Vij, Ankush; Kumar, Manjeet; Bala, Rajni; Meena, Ramovatar; Singh, Ajay; Thakur, Anup; Kumar, Akshay

2016-01-01

Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT. PMID:27759052

Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy

NASA Astrophysics Data System (ADS)

Singh, Bikramjeet; Kaur, Gurpreet; Singh, Paviter; Singh, Kulwinder; Kumar, Baban; Vij, Ankush; Kumar, Manjeet; Bala, Rajni; Meena, Ramovatar; Singh, Ajay; Thakur, Anup; Kumar, Akshay

2016-10-01

Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT.

Synthesis and in vitro evaluation of thiododecaborated α, α- cycloalkylamino acids for the treatment of malignant brain tumors by boron neutron capture therapy.

PubMed

Hattori, Yoshihide; Kusaka, Shintaro; Mukumoto, Mari; Ishimura, Miki; Ohta, Yoichiro; Takenaka, Hiroshi; Uehara, Kouki; Asano, Tomoyuki; Suzuki, Minoru; Masunaga, Shin-Ichiro; Ono, Koji; Tanimori, Shinji; Kirihata, Mitsunori

2014-12-01

Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11](2-)-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.

Thermal Neutron Capture onto the Stable Tungsten Isotopes

NASA Astrophysics Data System (ADS)

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

2012-02-01

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

Histamine reduces boron neutron capture therapy-induced mucositis in an oral precancer model.

PubMed

Monti Hughes, A; Pozzi, Ecc; Thorp, S I; Curotto, P; Medina, V A; Martinel Lamas, D J; Rivera, E S; Garabalino, M A; Farías, R O; Gonzalez, S J; Heber, E M; Itoiz, M E; Aromando, R F; Nigg, D W; Trivillin, V A; Schwint, A E

2015-09-01

Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1). Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs 55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interference effect between neutron direct and resonance capture reactions for neutron-rich nuclei

NASA Astrophysics Data System (ADS)

Minato, Futoshi; Fukui, Tokuro

2017-11-01

Interference effect of neutron capture cross section between the compound and direct processes is investigated. The compound process is calculated by resonance parameters and the direct process by the potential model. The interference effect is tested for neutron-rich 82Ge and 134Sn nuclei relevant to r-process and light nucleus 13C which is neutron poison in the s-process and produces long-lived radioactive nucleus 14C (T1/2 = 5700 y). The interference effects in those nuclei are significant around resonances, and low energy region if s-wave neutron direct capture is possible. Maxwellian averaged cross sections at kT = 30 and 300 keV are also calculated, and the interference effect changes the Maxwellian averaged capture cross section largely depending on resonance position.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakurai, Yoshinori, E-mail: yosakura@rri.kyoto-u.ac.jp; Tanaka, Hiroki; Kondo, Natsuko

2015-11-15

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

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

PubMed

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

2015-11-01

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

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

PubMed

Barth, Rolf F; Vicente, M Graca H; Harling, Otto K; Kiger, W S; Riley, Kent J; Binns, Peter J; Wagner, Franz M; Suzuki, Minoru; Aihara, Teruhito; Kato, Itsuro; Kawabata, Shinji

2012-08-29

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

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

PubMed Central

2012-01-01

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

CONVECTION ENHANCED DELIVERY OF CARBORANYLPORPHYRINS FOR NEUTRON CAPTURE THERAPY OF BRAIN TUMORS

PubMed Central

Kawabata, Shinji; Yang, Weilian; Wu, Gong; Huo, Tianyao; Binns, Peter J.; Riley, Kent J.; Ongayi, Owendi; Gottumukkala, Vijay; Vicente, M. Graça H.

2010-01-01

Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive 10B is irradiated with low energy thermal neutrons to produce α-particles (10B[n,α]7Li). Carboranylporphyrins are a class of substituted porphyrins containing multiple carborane clusters. Three of these have been evaluated in the present study: 5,10,15,20-tetra-(4-nido-carboranyphenyl)tetrabenzoporphyrin (H2TBP), 5,10,15,20-tetra-(4-nido-carboranylphenyl)porphyrin (H2TCP) and 5,15-di-[3,5-(nido-carboranylmethyl)phenyl]-porphyrin (H2DCP). The goals of this study were two-fold. First, to determine the biodistribution of H2TBP, H2TCP and H2DCP following intracerebral (i.c.) administration by means of short term (30 min) convection enhanced delivery (CED) or sustained delivery over 24 h by osmotic pumps to F98 glioma bearing rats. Second, to determine the efficacy of H2TCP and H2TBP as boron delivery agents for BNCT in F98 glioma bearing rats. Tumor boron concentrations immediately after i.c. osmotic pump delivery were high (36–88 µg/g) and they remained so at 24 h (62–103 µg/g) The corresponding normal brain concentrations were low (0.8–5.2 µg/g) and the blood and liver concentrations were all undetectable. Based on these data, therapy studies were initiated at the Massachusetts Institute of Technology (MIT) Research Reactor (MITRR) with H2TCP and H2TBP 24 h after CED or osmotic pump delivery. Mean survival times (MST) of untreated and irradiated control rats were 23±3 and 27±3 d, respectively, while animals that received H2TCP or H2TBP, followed by BNCT, had a MST of 35±4 d and 44±10 d, respectively, which were better than those obtained following i.v. administration of boronophenylalanine (37±3 d). However, since the tumor boron concentrations of the carboranylporphyrins were 3–5X > i.v. BPA (~25 µg/g), we had expected that the MSTs would have been greater. Histopathologic examination of brains of BNCT treated rats revealed

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

PubMed Central

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

2017-01-01

Objective: Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a 10BSH-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. Methods: We prepared the 10BSH-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 × 1012 n cm−2. Morphological and pathological analyses were performed on Day 14 after neutron irradiation. Results: Biodistribution results have revealed that 10B 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 10BSH-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. Conclusion: Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the 10BSH-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 10BSH 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. PMID:28406315

Characterization of the Gamma Response of a Cadmium Capture-gated Neutron Spectrometer

NASA Astrophysics Data System (ADS)

Hogan, Nathaniel; Rees, Lawrence; Czirr, Bart; Bastola, Suraj

2010-10-01

We have studied the gamma response of a newly developed capture-gated neutron spectrometer. Such spectrometers detect a dual signal from incoming neutrons, allowing for differentiation between other particles, such as gamma rays. The neutron provides a primary light pulse in either plastic or liquid scintillator through neutron-proton collisions. A capture material then delivers a second pulse as the moderated neutron captures in the intended material, which then de-excites with the release of gamma energy. The presented spectrometer alternates one centimeter thick plastic scintillators with sheets of cadmium inserted in between for neutron capture. The neutron capture in cadmium offers a release of gamma energy ˜ 9 MeV. To verify that the interaction was caused by a neutron, the response functions of both events must be well known. Due to the prior existence of many capture-gated neutron spectrometers, the proton recoil pulse has already been studied, but the capture pulse is unique to each spectrometer and must be measured. Experimental results agree with theoretical Monte-Carlo code, both suggesting that the optics and geometry of the spectrometer play a large role in its efficiency. Results prove promising for the efficiency of the spectrometer.

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

NASA Astrophysics Data System (ADS)

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

2005-05-01

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

Enhancing the detector for advanced neutron capture experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Couture, A.; Mosby, S.; Baramsai, B.

2015-05-28

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

Radiative neutron capture cross sections on 176Lu at DANCE

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Do-Kun; Jung, Joo-Young; Suk Suh, Tae, E-mail: suhsanta@catholic.ac.kr

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).more » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsieh, M; Liu, Y; Nie, L

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

Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy

PubMed Central

Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

2013-01-01

Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their 24Na and 38Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to 24Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive 24Na is mainly generated from 23Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood 24Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood 24Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood 24Na was determined using a germanium counter. The activity of 24Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood 24Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible. PMID:23392825

Induced radioactivity in the blood of cancer patients following Boron Neutron Capture Therapy.

PubMed

Fujiwara, Keiko; Kinashi, Yuko; Takahashi, Tomoyuki; Yashima, Hiroshi; Kurihara, Kouta; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Takahashi, Sentaro

2013-07-01

Since 1990, Boron Neutron Capture Therapy (BNCT) has been used for over 400 cancer patients at the Kyoto University Research Reactor Institute (KURRI). After BNCT, the patients are radioactive and their (24)Na and (38)Cl levels can be detected via a Na-I scintillation counter. This activity is predominantly due to (24)Na, which has a half-life of 14.96 h and thus remains in the body for extended time periods. Radioactive (24)Na is mainly generated from (23)Na in the target tissue that is exposed to the neutron beam in BNCT. The purpose of this study is to evaluate the relationship between the radioactivity of blood (24)Na following BNCT and the absorbed gamma ray dose in the irradiated field. To assess blood (24)Na, 1 ml of peripheral blood was collected from 30 patients immediately after the exposure, and the radioactivity of blood (24)Na was determined using a germanium counter. The activity of (24)Na in the blood correlated with the absorbed gamma ray doses in the irradiated field. For the same absorbed gamma ray dose in the irradiated field, the activity of blood (24)Na was higher in patients with neck or lung tumors than in patients with brain or skin tumors. The reasons for these findings are not readily apparent, but the difference in the blood volume and the ratio of bone to soft tissue in the irradiated field, as well as the dose that leaked through the clinical collimator, may be responsible.

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

PubMed

Dai, Congxin; Cai, Feng; Hwang, Kuo Chu; Zhou, Yongmao; Zhang, Zizhu; Liu, Xiaohai; Ma, Sihai; Yang, Yakun; Yao, Yong; Feng, Ming; Bao, Xinjie; Li, Guilin; Wei, Junji; Jiao, Yonghui; Wei, Zhenqing; Ma, Wenbin; Wang, Renzhi

2013-02-01

Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.

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

PubMed

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

1994-08-01

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

Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: a boron neutron capture therapy study.

PubMed

Gifford, Ian; Vreeland, Wyatt; Grdanovska, Slavica; Burgett, Eric; Kalinich, John; Vergara, Vernieda; Wang, C-K Chris; Maimon, Eric; Poster, Dianne; Al-Sheikhly, Mohamad

2014-06-01

The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined. Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays. Colony formation assays were utilized to evaluate the decrease in cell survival due to high-linear energy transfer (LET) particles resulting from (10)B thermal neutron capture. BCH delivery by means of encapsulation in a lipid bilayer resulted in a boron uptake of 35.2 ± 4.3 μg/10(9) cells, with minimal cytotoxic effects. PC-3 cells treated with BCH and exposed to a 9.4 × 10(11) n/cm(2) thermal neutron fluence yielded a 20-25% decrease in clonogenic capacity. The decreased survival is attributed to the generation of high-LET α particles and (7)Li nuclei that deposit energy in densely ionizing radiation tracks. Liposome-based delivery of BCH is capable of introducing sufficient boron to PC-3 cells for BNCT. High-LET α particles and (7)Li nuclei generated from (10)B thermal neutron capture significantly decrease colony formation ability in the targeted PC-3 cells.

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

PubMed

Wortmann, Birgit; Knorr, Jürgen

2012-08-01

In 2001 and 2003, at the University of Pavia, Italy, boron neutron capture therapy (BNCT) has been successfully used in the treatment of hepatic colorectal metastases (Pinelli et al., 2002; Zonta et al., 2006). The treatment procedure (TAOrMINA protocol) is characterised by the auto-transplantation and extracorporeal irradiation of the liver using a thermal neutron beam. The clinical use of this approach requires well founded data and an optimized irradiation facility. In order to start with this work and to decide upon its feasibility at the research reactor TRIGA Mainz, basic data and requirements have been considered (Wortmann, 2008). Computer calculations using the ATTILA (Transpire Inc. 2006) and MCNP (LANL, 2005) codes have been performed, including data from conventional radiation therapy, from the TAOrMINA approach, resulting in reasonable estimations. Basic data and requirements and optimal parameters have been worked out, especially for use at an optimized TRIGA irradiation facility (Wortmann, 2008). Advantages of the extracorporeal irradiation with auto-transplantation and the potential of an optimized irradiation facility could be identified. Within the requirements, turning the explanted organ over by 180° appears preferable to a whole side source, similar to a permanent rotation of the organ. The design study and the parameter optimization confirm the potential of this approach to treat metastases in explanted organs. The results do not represent actual treatment data but a first estimation. Although all specific values refer to the TRIGA Mainz, they may act as a useful guide for other types of neutron sources. The recommended modifications (Wortmann, 2008) show the suitability of TRIGA reactors as a radiation source for BNCT of extracorporeal irradiated and auto-transplanted organs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Beam shaping assembly design of 7Li(p,n)7Be neutron source for boron neutron capture therapy of deep-seated tumor.

PubMed

Zaidi, L; Belgaid, M; Taskaev, S; Khelifi, R

2018-05-31

The development of a medical facility for boron neutron capture therapy at Budker Institute of Nuclear Physics is under way. The neutron source is based on a tandem accelerator with vacuum insulation and lithium target. The proposed accelerator is conceived to deliver a proton beam around 10 mA at 2.3 MeV proton beam. To deliver a therapeutic beam for treatment of deep-seated tumors a typical Beam Shaping Assembly (BSA) based on the source specifications has been explored. In this article, an optimized BSA based on the 7 Li(p,n) 7 Be neutron production reaction is proposed. To evaluate the performance of the designed beam in a phantom, the parameters and the dose profiles in tissues due to the irradiation have been considered. In the simulations, we considered a proton energy of 2.3 MeV, a current of 10 mA, and boron concentrations in tumor, healthy tissues and skin of 52.5 ppm, 15 ppm and 22.5 ppm, respectively. It is found that, for a maximum punctual healthy tissue dose seated to 11 RBE-Gy, a mean dose of 56.5 RBE Gy with a minimum of 52.2 RBE Gy can be delivered to a tumor in 40 min, where the therapeutic ratio is estimated to 5.38. All of these calculations were carried out using the Monte Carlo MCNP code. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of new boron-containing chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

PubMed

Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

2014-03-01

New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were investigated in tumor-bearing mice. The time to maximum accumulation of compound 13 in tumor tissue was one-fourth of that of compound 9, and compound 13 showed rapid clearance from normal tissues within 24h after injection. The in vivo therapeutic efficacy of PDT using 13 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3h after injection of 13. Tumor growth was significantly inhibited by PDT using 13. These results suggested that 13 might be a good candidate for both PDT and BNCT of cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

DOEpatents

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

1964-04-14

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

Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas

PubMed Central

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

2009-01-01

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

Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma.

PubMed

Futamura, Gen; Kawabata, Shinji; Nonoguchi, Naosuke; Hiramatsu, Ryo; Toho, Taichiro; Tanaka, Hiroki; Masunaga, Shin-Ichiro; Hattori, Yoshihide; Kirihata, Mitsunori; Ono, Koji; Kuroiwa, Toshihiko; Miyatake, Shin-Ichi

2017-01-23

Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. We developed a novel boron-10 containing sodium borocaptate (BSH) derivative, 1-amino-3-fluorocyclobutane-1-carboxylic acid (ACBC)-BSH. ACBC is a tumor selective synthetic amino acid. The purpose of this study was to assess the biodistribution of ACBC-BSH and its therapeutic efficacy following Boron Neutron Capture Therapy (BNCT) of the F98 rat glioma. We evaluated the biodistribution of three boron-10 compounds, ACBC-BSH, BSH and boronophenylalanine (BPA), in vitro and in vivo, following intravenous (i.v.) administration and intratumoral (i.t.) convection-enhanced delivery (CED) in F98 rat glioma bearing rats. For BNCT studies, rats were stratified into five groups: untreated controls, neutron-irradiation controls, BNCT with BPA/i.v., BNCT with ACBC-BSH/CED, and BNCT concomitantly using BPA/i.v. and ACBC-BSH/CED. In vitro, ACBC-BSH attained higher cellular uptake F98 rat glioma cells compared with BSH. In vivo biodistribution studies following i.v. administration and i.t. CED of ACBC-BSH attained significantly higher boron concentrations than that of BSH, but much lower than that of BPA. However, following convection enhanced delivery (CED), ACBC-BSH attained significantly higher tumor concentrations than BPA. The i.t. boron-10 concentrations were almost equal between the ACBC-BSH/CED group and BPA/i.v. group of rats. The tumor/brain boron-10 concentration ratio was higher with ACBC-BSH/CED than that of BPA/i.v. group. Based on these data, BNCT studies were carried out in F98 glioma bearing rats using BPA/i.v. and ACBC-BSH/CED as the delivery agents. The corresponding mean survival times were 37.4 ± 2.6d and 44.3 ± 8.0d, respectively, and although modest, these differences were statistically significant. Our findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent.

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

PubMed

Alberti, Diego; Protti, Nicoletta; Toppino, Antonio; Deagostino, Annamaria; Lanzardo, Stefania; Bortolussi, Silva; Altieri, Saverio; Voena, Claudia; Chiarle, Roberto; Geninatti Crich, Simonetta; Aime, Silvio

2015-04-01

This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation. Copyright © 2015 Elsevier Inc. All rights reserved.

In Vivo Boron Uptake Determination for Boron Neutron Capture Synovectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1999-06-06

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

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

PubMed

Takahara, Kiyoshi; Inamoto, Teruo; Minami, Koichiro; Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

2015-01-01

Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean ± SD 6.9 ± 1.5 vs 12.7 ± 4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model

PubMed Central

Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

2015-01-01

Purpose Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa. PMID:26325195

Neutron-capture Nucleosynthesis in the First Stars

NASA Astrophysics Data System (ADS)

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

2014-04-01

Recent studies suggest that metal-poor stars enhanced in carbon but containing low levels of neutron-capture elements may have been among the first to incorporate the nucleosynthesis products of the first generation of stars. We have observed 16 stars with enhanced carbon or nitrogen using the MIKE Spectrograph on the Magellan Telescopes at Las Campanas Observatory and the Tull Spectrograph on the Smith Telescope at McDonald Observatory. We present radial velocities, stellar parameters, and detailed abundance patterns for these stars. Strontium, yttrium, zirconium, barium, europium, ytterbium, and other heavy elements are detected. In four stars, these heavy elements appear to have originated in some form of r-process nucleosynthesis. In one star, a partial s-process origin is possible. The origin of the heavy elements in the rest of the sample cannot be determined unambiguously. The presence of elements heavier than the iron group offers further evidence that zero-metallicity rapidly rotating massive stars and pair instability supernovae did not contribute substantial amounts of neutron-capture elements to the regions where the stars in our sample formed. If the carbon- or nitrogen-enhanced metal-poor stars with low levels of neutron-capture elements were enriched by products of zero-metallicity supernovae only, then the presence of these heavy elements indicates that at least one form of neutron-capture reaction operated in some of the first stars. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile, and The McDonald Observatory of The University of Texas at Austin.

Early clinical experience utilizing scintillator with optical fiber (SOF) detector in clinical boron neutron capture therapy: its issues and solutions.

PubMed

Ishikawa, Masayori; Yamamoto, Tetsuya; Matsumura, Akira; Hiratsuka, Junichi; Miyatake, Shin-Ichi; Kato, Itsuro; Sakurai, Yoshinori; Kumada, Hiroaki; Shrestha, Shubhechha J; Ono, Koji

2016-08-09

Real-time measurement of thermal neutrons in the tumor region is essential for proper evaluation of the absorbed dose in boron neutron capture therapy (BNCT) treatment. The gold wire activation method has been routinely used to measure the neutron flux distribution in BNCT irradiation, but a real-time measurement using gold wire is not possible. To overcome this issue, the scintillator with optical fiber (SOF) detector has been developed. The purpose of this study is to demonstrate the feasibility of the SOF detector as a real-time thermal neutron monitor in clinical BNCT treatment and also to report issues in the use of SOF detectors in clinical practice and their solutions. Clinical measurements using the SOF detector were carried out in 16 BNCT clinical trial patients from December 2002 until end of 2006 at the Japanese Atomic Energy Agency (JAEA) and Kyoto University Research Reactor Institute (KURRI). The SOF detector worked effectively as a real-time thermal neutron monitor. The neutron fluence obtained by the gold wire activation method was found to differ from that obtained by the SOF detector. The neutron fluence obtained by the SOF detector was in better agreement with the expected fluence than with gold wire activation. The estimation error for the SOF detector was small in comparison to the gold wire measurement. In addition, real-time monitoring suggested that the neutron flux distribution and intensity at the region of interest (ROI) may vary due to the reactor condition, patient motion and dislocation of the SOF detector. Clinical measurements using the SOF detector to measure thermal neutron flux during BNCT confirmed that SOF detectors are effective as a real-time thermal neutron monitor. To minimize the estimation error due to the displacement of the SOF probe during treatment, a loop-type SOF probe was developed.

Neutron Capture Measurements on 97Mo with the DANCE Array

NASA Astrophysics Data System (ADS)

Walker, Carrie L.

Neutron capture is a process that is crucial to understanding nucleosynthesis, reactors, and nuclear weapons. Precise knowledge of neutron capture cross-sections and level densities is necessary in order to model these high-flux environments. High-confidence spin and parity assignments for neutron resonances are of critical importance to this end. For nuclei in the A=100 mass region, the p-wave neutron strength function is at a maximum, and the s-wave strength function is at a minimum, producing up to six possible Jpi combinations. Parity determination becomes important to assigning spins in this mass region, and the large number of spin groups adds complexity to the problem. In this work, spins and parities for 97Mo resonances are assigned, and best fit models for photon strength function and level density are determined. The neutron capture-cross section for 97Mo is also determined, as are resonance parameters for neutron energies ranging from 16 eV to 2 keV.

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

Biodistribution of sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) in an oral cancer model.

PubMed

Garabalino, Marcela A; Heber, Elisa M; Monti Hughes, Andrea; González, Sara J; Molinari, Ana J; Pozzi, Emiliano C C; Nievas, Susana; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Bauer, William; Trivillin, Verónica A; Schwint, Amanda E

2013-08-01

Boron neutron capture therapy (BNCT) is based on selective accumulation of ¹⁰B carriers in tumor followed by neutron irradiation. We previously proved the therapeutic success of BNCT mediated by the boron compounds boronophenylalanine and sodium decahydrodecaborate (GB-10) in the hamster cheek pouch oral cancer model. Based on the clinical relevance of the boron carrier sodium borocaptate (BSH) and the knowledge that the most effective way to optimize BNCT is to improve tumor boron targeting, the specific aim of this study was to perform biodistribution studies of BSH in the hamster cheek pouch oral cancer model and evaluate the feasibility of BNCT mediated by BSH at nuclear reactor RA-3. The general aim of these studies is to contribute to the knowledge of BNCT radiobiology and optimize BNCT for head and neck cancer. Sodium borocaptate (50 mg ¹⁰B/kg) was administered to tumor-bearing hamsters. Groups of 3-5 animals were killed humanely at nine time-points, 3-12 h post-administration. Samples of blood, tumor, precancerous pouch tissue, normal pouch tissue and other clinically relevant normal tissues were processed for boron measurement by optic emission spectroscopy. Tumor boron concentration peaked to therapeutically useful boron concentration values of 24-35 ppm. The boron concentration ratio tumor/normal pouch tissue ranged from 1.1 to 1.8. Pharmacokinetic curves showed that the optimum interval between BSH administration and neutron irradiation was 7-11 h. It is concluded that BNCT mediated by BSH at nuclear reactor RA-3 would be feasible.

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

PubMed

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

2006-02-01

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

Development of Monte Carlo based real-time treatment planning system with fast calculation algorithm for boron neutron capture therapy.

PubMed

Takada, Kenta; Kumada, Hiroaki; Liem, Peng Hong; Sakurai, Hideyuki; Sakae, Takeji

2016-12-01

We simulated the effect of patient displacement on organ doses in boron neutron capture therapy (BNCT). In addition, we developed a faster calculation algorithm (NCT high-speed) to simulate irradiation more efficiently. We simulated dose evaluation for the standard irradiation position (reference position) using a head phantom. Cases were assumed where the patient body is shifted in lateral directions compared to the reference position, as well as in the direction away from the irradiation aperture. For three groups of neutron (thermal, epithermal, and fast), flux distribution using NCT high-speed with a voxelized homogeneous phantom was calculated. The three groups of neutron fluxes were calculated for the same conditions with Monte Carlo code. These calculated results were compared. In the evaluations of body movements, there were no significant differences even with shifting up to 9mm in the lateral directions. However, the dose decreased by about 10% with shifts of 9mm in a direction away from the irradiation aperture. When comparing both calculations in the phantom surface up to 3cm, the maximum differences between the fluxes calculated by NCT high-speed with those calculated by Monte Carlo code for thermal neutrons and epithermal neutrons were 10% and 18%, respectively. The time required for NCT high-speed code was about 1/10th compared to Monte Carlo calculation. In the evaluation, the longitudinal displacement has a considerable effect on the organ doses. We also achieved faster calculation of depth distribution of thermal neutron flux using NCT high-speed calculation code. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2011-12-01

Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg). Copyright © 2011 Elsevier Ltd. All rights reserved.

Towards boron neutron capture therapy: the formulation and preliminary in vitro evaluation of liposomal vehicles for the therapeutic delivery of the dequalinium salt of bis-nido-carborane.

PubMed

Theodoropoulos, Dimitrios; Rova, Aikaterini; Smith, James R; Barbu, Eugen; Calabrese, Gianpiero; Vizirianakis, Ioannis S; Tsibouklis, John; Fatouros, Dimitrios G

2013-11-15

Liposomes of phosphatidylcholine or of dimyristoylphosphatidylcholine that incorporate bis-nido-carborane dequalinium salt are stable in physiologically relevant media and have in vitro toxicity profiles that appear to be compatible with potential therapeutic applications. These features render the structures suitable candidate boron-delivery vehicles for evaluation in the boron neutron capture therapy of cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma.

PubMed

Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

2016-10-01

Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels.

PubMed

Molinari, Ana J; Thorp, Silvia I; Portu, Agustina M; Saint Martin, Gisela; Pozzi, Emiliano C C; Heber, Elisa M; Bortolussi, Silva; Itoiz, Maria E; Aromando, Romina F; Monti Hughes, Andrea; Garabalino, Marcela A; Altieri, Saverio; Trivillin, Verónica A; Schwint, Amanda E

2015-01-01

We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (Th+ Seq-BNCT) or Seq-Beam Only (Th+ Seq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. Th+ Seq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. Th+ Seq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control.

Synthesis and biological evaluation of new BSH-conjugated chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

PubMed

Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

2014-11-01

New disodium mercaptoundecahydro-closo-dodecaborate (BSH)-conjugated chlorin derivatives 11, 12, 16 and 20 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized. The in vivo biodistribution and clearance of 11, 12, 16 and 20 were investigated in tumor-bearing mice. Compounds 12 and 16 showed good tumor-selective accumulation among the four derivatives. The time to maximum accumulation of compound 16 in tumor tissue was one-fourth of that of compound 12, and clearance from normal tissues of compound 16 was similar to that of compound 12. The in vivo therapeutic efficacy of PDT using 16, which has twice as many boron atoms as 12, was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 6h after injection of 16. Tumor growth was significantly inhibited by PDT using 16. These results suggested that 16 is a good candidate for both PDT and BNCT of cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed Central

2010-01-01

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

Neutron Capture Experiments on Unstable Nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwantes, Jon M.; Sudowe, Ralf; Folden, Charles M., III

2005-01-15

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

242Pu absolute neutron-capture cross section measurement

NASA Astrophysics Data System (ADS)

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

2017-09-01

The absolute neutron-capture cross section of 242Pu was measured at the Los Alamos Neutron Science Center using the Detector for Advanced Neutron-Capture Experiments array along with a compact parallel-plate avalanche counter for fission-fragment detection. During target fabrication, a small amount of 239Pu was added to the active target so that the absolute scale of the 242Pu(n,γ) cross section could be set according to the known 239Pu(n,f) resonance at En,R = 7.83 eV. The relative scale of the 242Pu(n,γ) cross section covers four orders of magnitude for incident neutron energies from thermal to ≈ 40 keV. The cross section reported in ENDF/B-VII.1 for the 242Pu(n,γ) En,R = 2.68 eV resonance was found to be 2.4% lower than the new absolute 242Pu(n,γ) cross section.

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

PubMed

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

2015-12-01

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

Progress on the Europium Neutron-Capture Study using DANCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agvaanluvsan, U; Becker, J A; Macri, R A

2006-09-05

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

Estimation of relative biological effectiveness for boron neutron capture therapy using the PHITS code coupled with a microdosimetric kinetic model

PubMed Central

Horiguchi, Hironori; Sato, Tatsuhiko; Kumada, Hiroaki; Yamamoto, Tetsuya; Sakae, Takeji

2015-01-01

Abstract The absorbed doses deposited by boron neutron capture therapy (BNCT) can be categorized into four components: α and 7Li particles from the 10B(n, α)7Li reaction, 0.54-MeV protons from the 14N(n, p)14C reaction, the recoiled protons from the 1H(n, n) 1H reaction, and photons from the neutron beam and 1H(n, γ)2H reaction. For evaluating the irradiation effect in tumors and the surrounding normal tissues in BNCT, it is of great importance to estimate the relative biological effectiveness (RBE) for each dose component in the same framework. We have, therefore, established a new method for estimating the RBE of all BNCT dose components on the basis of the microdosimetric kinetic model. This method employs the probability density of lineal energy, y, in a subcellular structure as the index for expressing RBE, which can be calculated using the microdosimetric function implemented in the particle transport simulation code (PHITS). The accuracy of this method was tested by comparing the calculated RBE values with corresponding measured data in a water phantom irradiated with an epithermal neutron beam. The calculation technique developed in this study will be useful for biological dose estimation in treatment planning for BNCT. PMID:25428243

FY07 LDRD Final Report Neutron Capture Cross-Section Measurements at DANCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, W; Agvaanluvsan, U; Wilk, P

2008-02-08

We have measured neutron capture cross sections intended to address defense science problems including mix and the Quantification of Margins and Uncertainties (QMU), and provide details about statistical decay of excited nuclei. A major part of this project included developing the ability to produce radioactive targets. The cross-section measurements were made using the white neutron source at the Los Alamos Neutron Science Center, the detector array called DANCE (The Detector for Advanced Neutron Capture Experiments) and targets important for astrophysics and stockpile stewardship. DANCE is at the leading edge of neutron capture physics and represents a major leap forward inmore » capability. The detector array was recently built with LDRD money. Our measurements are a significant part of the early results from the new experimental DANCE facility. Neutron capture reactions are important for basic nuclear science, including astrophysics and the statistics of the {gamma}-ray cascades, and for applied science, including stockpile science and technology. We were most interested in neutron capture with neutron energies in the range between 1 eV and a few hundred keV, with targets important to basic science, and the s-process in particular. Of particular interest were neutron capture cross-section measurements of rare isotopes, especially radioactive isotopes. A strong collaboration between universities and Los Alamos due to the Academic Alliance was in place at the start of our project. Our project gave Livermore leverage in focusing on Livermore interests. The Lawrence Livermore Laboratory did not have a resident expert in cross-section measurements; this project allowed us to develop this expertise. For many radionuclides, the cross sections for destruction, especially (n,{gamma}), are not well known, and there is no adequate model that describes neutron capture. The modeling problem is significant because, at low energies where capture reactions are important, the

Measuring and Validating Neutron Capture Cross Sections Using a Lead Slowing-Down Spectrometer

NASA Astrophysics Data System (ADS)

Thompson, Nicholas

Accurate nuclear data is essential for the modeling, design, and operation of nuclear systems. In this work, the Rensselaer Polytechnic Institute (RPI) Lead Slowing-Down Spectrometer (LSDS) at the Gaerttner Linear Accelerator Center (LINAC) was used to measure neutron capture cross sections and validate capture cross sections in cross section libraries. The RPI LINAC was used to create a fast burst of neutrons in the center of the LSDS, a large cube of high purity lead. A sample and YAP:Ce scintillator were placed in the LSDS, and as neutrons lost energy through scattering interactions with the lead, the scintillator detected capture gammas resulting from neutron capture events in the sample. Samples of silver, gold, cobalt, iron, indium, molybdenum, niobium, nickel, tin, tantalum, and zirconium were measured. Data was collected as a function of time after neutron pulse, or slowing-down time, which is correlated to average neutron energy. An analog and a digital data acquisition system collected data simultaneously, allowing for collection of pulse shape information as well as timing. Collection of digital data allowed for pulse shape analysis after the experiment. This data was then analyzed and compared to Monte Carlo simulations to validate the accuracy of neutron capture cross section libraries. These measurements represent the first time that neutron capture cross sections have been measured using an LSDS in the United States, and the first time tools such as coincidence measurements and pulse height weighting have been applied to measurements of neutron capture cross sections using an LSDS. Significant differences between measurement results and simulation results were found in multiple materials, and some errors in nuclear data libraries have already been identified due to these measurements.

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

PubMed Central

Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

2016-01-01

Purpose Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. Methods B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. Results B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. Conclusions B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on tumor hypoxic metabolism, and further studies are warranted to evaluate this compound and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma. PMID:27401411

Feasibility of the Utilization of BNCT in the Fast Neutron Therapy Beam at Fermilab

DOE R&D Accomplishments Database

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

2000-06-01

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.

Boron detection from blood samples by ICP-AES and ICP-MS during boron neutron capture therapy.

PubMed

Linko, S; Revitzer, H; Zilliacus, R; Kortesniemi, M; Kouri, M; Savolainen, S

2008-01-01

The concept of boron neutron capture therapy (BNCT) involves infusion of a (10)B containing tracer into the patient's bloodstream followed by local neutron irradiation(s). Accurate estimation of the blood boron level for the treatment field before irradiation is required. Boron concentration can be quantified by inductively coupled plasma atomic emission spectrometry (ICP-AES), mass spectrometry (ICP-MS), spectrofluorometric and direct current atomic emission spectrometry (DCP-AES) or by prompt gamma photon detection methods. The blood boron concentrations were analysed and compared using ICP-AES and ICP-MS to ensure congruency of the results if the analysis had to be changed during the treatment, e.g. for technical reasons. The effect of wet-ashing on the results was studied in addition. The mean of all samples analysed with ICP-MS was 5.8 % lower than with ICP-AES coupled to wet-ashing (R (2) = 0.88). Without wet-ashing, the mean of all samples analysed with ICP-MS was 9.1 % higher than with ICP-AES (R (2) = 0.99). Boron concentration analysed from whole blood samples with ICP-AES correlated well with the values of ICP-MS with wet-ashing of the sample matrix, which is generally considered the reference method. When using these methods in parallel at certain intervals during the treatments, reliability of the blood boron concentration values remains satisfactory, taking into account the required accuracy of dose determination in the irradiation of cancer patients.

Neutron Capture gamma ENDF libraries for modeling and identification of neutron sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sleaford, B

2007-10-29

There are a number of inaccuracies and data omissions with respect to gammas from neutron capture in the ENDF libraries used as field reference information and by modeling codes used in JTOT. As the use of Active Neutron interrogation methods is expanded, these shortfalls become more acute. A new, more accurate and complete evaluated experimental database of gamma rays (over 35,000 lines for 262 isotopes up to U so far) from thermal neutron capture has recently become available from the IAEA. To my knowledge, none of this new data has been installed in ENDF libraries and disseminated. I propose tomore » upgrade libraries of {sup 184,186}W, {sup 56}Fe, {sup 204,206,207}Pb, {sup 104}Pd, and {sup 19}F the 1st year. This will involve collaboration with Richard Firestone at LBL in evaluating the data and installing it in the libraries. I will test them with the transport code MCNP5.« less

Nuclear magnetic resonance study of Gd-based nanoparticles to tag boron compounds in boron neutron capture therapy

NASA Astrophysics Data System (ADS)

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

2011-04-01

We report the investigation of new organic complexes containing a magnetic moment (Gd-based molecular nanomagnets), which can serve the double purpose of acting as boron neutron capture therapy (BNCT) agents, and at the same time act as contrast agents to detect the molecule in the tissue by a proton magnetic resonance imaging (MRI). We also explore the possibility of monitoring the concentration of the BNCT agent directly via proton and boron NMR relaxation. The absorption of 10B-enriched molecules inside tumoral liver tissues has been shown by NMR measurements and confirmed by α spectroscopy. A new molecular Gd-tagged nanomagnet and BNCT agent (GdBPA) has been synthesized and characterized measuring its relaxivity R1 between 10 kHz and 66 MHz, and its use as a contrast agent in MRI has been demonstrated. The NMR-based evidence of the absorption of GdBPA into living tumoral cells is also shown.

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

PubMed

Fujimoto, T; Ichikawa, H; Akisue, T; Fujita, I; Kishimoto, K; Hara, H; Imabori, M; Kawamitsu, H; Sharma, P; Brown, S C; Moudgil, B M; Fujii, M; Yamamoto, T; Kurosaka, M; Fukumori, Y

2009-07-01

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

Lithium Nitride Synthesized by in situ Lithium Deposition and Ion Implantation for Boron Neutron Capture Therapy

NASA Astrophysics Data System (ADS)

Ishitama, Shintaro; Baba, Yuji; Fujii, Ryo; Nakamura, Masaru; Imahori, Yoshio

Li3N synthesis on Li deposition layer was conducted without H2O and O2 by in situ lithium deposition in high vacuum chamber of 10-6 Pa and ion implantation techniques and the thermo-chemical stability of the Li3N/Li/Cu tri-layered target for Boron Neutron Capture Therapy (BNCT) under laser heating and air exposure was characterized by X-ray photoelectron spectroscopy (XPS). Following conclusions were derived; (1) Li3N/Li/Cu tri-layered target with very low oxide and carbon contamination was synthesized by in situ lithium vacuum deposition and N2+ ion implantation without H2O and O2 additions, (2) The starting temperature of evaporation of Li3N/Li/Cu tri-layered target increased by 120K compared to that of the Li/Cu target and (3) Remarkable oxidation and carbon contamination were observed on the surface of Li3N/Li/Cu after air exposure and these contaminated compositions was not removed by Ar+ heavy sputtering.

Boron Neutron Capture Therapy for HER2+ breast cancers: A feasibility study evaluating BNCT for potential role in breast conservation therapies

NASA Astrophysics Data System (ADS)

Jenkins, Peter Anthony

A novel Boron Neutron Capture Therapy (BNCT) regimen for the treatment of HER2+ breast cancers has been proposed as an alternative to whole breast irradiation for breast conservation therapy patients. The proposed therapy regimen is based on the assumed production of boron delivery agents that would be synthesized from compounds of Trastuzumab (Herceptin ®) and oligomeric phosphate diesters (OPDs). The combination of the anti-HER2 monoclonal antibody and the high boron loading capability of OPDs has led to the assumption that boron could be delivered to the HER2+ cancer cells at Tumor to Healthy Tissue ratios (T:H) of up to 35:1 and boron concentrations above 50 μg/g. This significantly increased boron delivery efficiency has opened new BNCT possibilities. This proof of concept study examined treatment parameters derived as the results in previous efforts in the context of patient-specific geometry and compared calculated dose results to those observed during actual patient therapy. These results were based on dose calculations performed with a set of calculated Kerma coefficients derived from tissues specific to the regions of interest for breast cancer. A comparison was made of the dose to the tumor region, the patient's skin, and the peripheral organs. The results of this study demonstrated that, given the performance of the proposed boron delivery agent, the BNCT treatment regimen is feasible. The feasibility is based on the findings that the equivalent dose could be delivered to the treatment volume with less dose to the skin and peripheral organs. This is anticipated to improve the treatment outcomes by maintaining local control of tumor cells while reducing dose to healthy tissues.

Review of Livermore-Led Neutron Capture Studies Using DANCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, W; Sheets, S; Agvaanluvsan, U

2007-05-11

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

DANCEing with the Stars: Measuring Neutron Capture on Unstable Isotopes with DANCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Couture, A.; Bond, E.; Bredeweg, T. A.

2009-03-10

Isotopes heavier than iron are known to be produced in stars through neutron capture processes. Two major processes, the slow (s) and rapid (r) processes are each responsible for 50% of the abundances of the heavy isotopes. The neutron capture cross sections of the isotopes on the s process path reveal information about the expected abundances of the elements as well as stellar conditions and dynamics. Until recently, measurements on unstable isotopes, which are most important for determining stellar temperatures and reaction flow, have not been experimentally feasible. The Detector for Advance Neutron Capture Experiments (DANCE) located at the Losmore » Alamos Neutron Science Center (LANSCE) was designed to perform time-of-flight neutron capture measurements on unstable isotopes for nuclear astrophysics, stockpile stewardship, and reactor development. DANCE is a 4-{pi}BaF{sub 2} scintillator array which can perform measurements on sub-milligram samples of isotopes with half-lives as short as a few hundred days. These cross sections are critical for advancing our understanding of the production of the heavy isotopes.« less

Boron neutron capture therapy for newly diagnosed glioblastoma multiforme: an assessment of clinical potential

PubMed Central

Sköld, K; Gorlia, T; Pellettieri, L; Giusti, V; H-Stenstam, B; Hopewell, J W

2010-01-01

The purpose of this study was to assess the potential of boron neutron capture therapy (BNCT), with a 6-h infusion of the boron carrier l-boronophenylalanine as a fructose preparation (BPA-f), as first-line radiotherapy for newly diagnosed glioblastoma multiforme (GBM). Patient survival data from a Phase II study using BNCT were compared with retrospective data from the two arms of a Phase III study using conventional radiotherapy (RT) in the reference arm and using RT plus concomitant and adjuvant medication with temozolomide (TMZ) in the experimental arm, and were also compared with small subgroups of these patients for whom the methylation status of the MGMT (O6-methylguanine–DNA methyltransferase) DNA repair gene was known. Differences in the baseline characteristics, salvage therapy after recurrence and levels of severe adverse events were also considered. The results indicate that BNCT offers a treatment that is at least as effective as conventional RT alone. For patients with an unmethylated MGMT DNA repair gene, a possible clinical advantage of BNCT over RT/TMZ was suggested. BNCT is a single-day treatment, which is of convenience to patients, with mild side effects, which would offer an initial 6 weeks of good-quality life during the time when patients would otherwise be undergoing daily treatments with RT and TMZ. It is suggested that the use of BNCT with a 6-h infusion of BPA-f should be explored in a stratified randomised Phase II trial in which patients with the unmethylated MGMT DNA repair gene are offered BNCT in the experimental arm and RT plus TMZ in the reference arm. PMID:20603410

Neutron capture on short-lived nuclei via the surrogate (d,pγ) reaction

NASA Astrophysics Data System (ADS)

Cizewski, Jolie A.; Ratkiewicz, Andrew

2018-05-01

Rapid r-process nucleosynthesis is responsible for the creation of about half of the elements heavier than iron. Neutron capture on shortlived nuclei in cold processes or during freeze out from hot processes can have a significant impact on the final observed r-process abundances. We are validating the (d,pγ) reaction as a surrogate for neutron capture with measurements on 95Mo targets and a focus on discrete transitions. The experimental results have been analyzed within the Hauser-Feshbach approach with non-elastic breakup of the deuteron providing a neutron to be captured. Preliminary results support the (d,pγ) reaction as a valid surrogate for neutron capture. We are poised to measure the (d,pγ) reaction in inverse kinematics with unstable beams following the development of the experimental techniques.

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

PubMed

Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito; Hiratsuka, Junichi; Yoshimura, Kenichi; Niimi, Miyuki; Kimura, Yoshihiro; Ariyoshi, Yasunori; Haginomori, Shin-Ichi; Sakurai, Yoshinori; Kinashi, Yuko; Masunaga, Shin-Ichiro; Fukushima, Masanori; Ono, Koji; Maruhashi, Akira

2014-01-01

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

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

PubMed Central

Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito; Hiratsuka, Junichi; Yoshimura, Kenichi; Niimi, Miyuki; Kimura, Yoshihiro; Ariyoshi, Yasunori; Haginomori, Shin-ichi; Sakurai, Yoshinori; Kinashi, Yuko; Masunaga, Shin-ichiro; Fukushima, Masanori; Ono, Koji; Maruhashi, Akira

2014-01-01

We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10–12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7–40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted. PMID:23955053

Simple, empirical approach to predict neutron capture cross sections from nuclear masses

NASA Astrophysics Data System (ADS)

Couture, A.; Casten, R. F.; Cakirli, R. B.

2017-12-01

Background: Neutron capture cross sections are essential to understanding the astrophysical s and r processes, the modeling of nuclear reactor design and performance, and for a wide variety of nuclear forensics applications. Often, cross sections are needed for nuclei where experimental measurements are difficult. Enormous effort, over many decades, has gone into attempting to develop sophisticated statistical reaction models to predict these cross sections. Such work has met with some success but is often unable to reproduce measured cross sections to better than 40 % , and has limited predictive power, with predictions from different models rapidly differing by an order of magnitude a few nucleons from the last measurement. Purpose: To develop a new approach to predicting neutron capture cross sections over broad ranges of nuclei that accounts for their values where known and which has reliable predictive power with small uncertainties for many nuclei where they are unknown. Methods: Experimental neutron capture cross sections were compared to empirical mass observables in regions of similar structure. Results: We present an extremely simple method, based solely on empirical mass observables, that correlates neutron capture cross sections in the critical energy range from a few keV to a couple hundred keV. We show that regional cross sections are compactly correlated in medium and heavy mass nuclei with the two-neutron separation energy. These correlations are easily amenable to predict unknown cross sections, often converting the usual extrapolations to more reliable interpolations. It almost always reproduces existing data to within 25 % and estimated uncertainties are below about 40 % up to 10 nucleons beyond known data. Conclusions: Neutron capture cross sections display a surprisingly strong connection to the two-neutron separation energy, a nuclear structure property. The simple, empirical correlations uncovered provide model-independent predictions of

The possible use of a spallation neutron source for neutron capture therapy with epithermal neutrons.

PubMed

Grusell, E; Condé, H; Larsson, B; Rönnqvist, T; Sornsuntisook, O; Crawford, J; Reist, H; Dahl, B; Sjöstrand, N G; Russel, G

1990-01-01

Spallation is induced in a heavy material by 72-MeV protons. The resulting neutrons can be characterized by an evaporation spectrum with a peak energy of less than 2 MeV. The neutrons are moderated in two steps: first in iron and then in carbon. Results from neutron fluence measurements in a perspex phantom placed close to the moderator are presented. Monte Carlo calculations of neutron fluence in a water phantom are also presented under some chosen configurations of spallation source and moderator. The calculations and measurements are in good agreement and show that, for proton currents of less than 0.5 mA, useful thermal-neutron fluences are attainable in the depth of the brain. However, the dose contribution from the unavoidable gamma background component has not been included in the present investigation.

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

PubMed Central

Morris, G M; Smith, D R; Patel, H; Chandra, S; Morrison, G H; Hopewell, J W; Rezvani, M; Micca, P L; Coderre, J A

2000-01-01

Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,α)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as

First Evaluation of the Biologic Effectiveness Factors of Boron Neutron Capture Therapy (BNCT) in a Human Colon Carcinoma Cell Line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.a; National Research Council; Crivello, Martin

2011-01-01

Purpose: DNA lesions produced by boron neutron capture therapy (BNCT) and those produced by gamma radiation in a colon carcinoma cell line were analyzed. We have also derived the relative biologic effectiveness factor (RBE) of the neutron beam of the RA-3- Argentine nuclear reactor, and the compound biologic effectiveness (CBE) values for p-boronophenylalanine ({sup 10}BPA) and for 2,4-bis ({alpha},{beta}-dihydroxyethyl)-deutero-porphyrin IX ({sup 10}BOPP). Methods and Materials: Exponentially growing human colon carcinoma cells (ARO81-1) were distributed into the following groups: (1) BPA (10 ppm {sup 10}B) + neutrons, (2) BOPP (10 ppm {sup 10}B) + neutrons, (3) neutrons alone, and (4) gammamore » rays ({sup 60}Co source at 1 Gy/min dose-rate). Different irradiation times were used to obtain total absorbed doses between 0.3 and 5 Gy ({+-}10%) (thermal neutrons flux = 7.5 10{sup 9} n/cm{sup 2} sec). Results: The frequency of micronucleated binucleated cells and the number of micronuclei per micronucleated binucleated cells showed a dose-dependent increase until approximately 2 Gy. The response to gamma rays was significantly lower than the response to the other treatments (p < 0.05). The irradiations with neutrons alone and neutrons + BOPP showed curves that did not differ significantly from, and showed less DNA damage than, irradiation with neutrons + BPA. A decrease in the surviving fraction measured by 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide (MTT) assay as a function of the absorbed dose was observed for all the treatments. The RBE and CBE factors calculated from cytokinesis block micronucleus (CBMN) and MTT assays were, respectively, the following: beam RBE: 4.4 {+-} 1.1 and 2.4 {+-} 0.6; CBE for BOPP: 8.0 {+-} 2.2 and 2.0 {+-} 1; CBE for BPA: 19.6 {+-} 3.7 and 3.5 {+-} 1.3. Conclusions: BNCT and gamma irradiations showed different genotoxic patterns. To our knowledge, these values represent the first experimental ones obtained for the RA-3

Stellar Neutron Capture Cross Sections of the Lu and Hf Isotopes

NASA Astrophysics Data System (ADS)

Wisshak, K.; Voss, F.; Käppeler, F.; Kazakov, L.; Krtička, M.

2005-05-01

The neutron capture cross sections of 175,176Lu and 176,177,178,179,180Hf have been measured in the energy range from 3 to 225 keV at the Karlsruhe 3.7 MV Van de Graaff accelerator relative to the gold standard. Neutrons were produced by the 7Li(p,n)7Be reaction and capture events were detected by the Karlsruhe 4πBaF2 detector. The cross section ratios could be determined with uncertainties between 0.9 and 1.8% about a factor of five more accurate than previous data. A strong population of isomeric states was found in neutron capture of the Hf isotopes, which are only partially explained by CASINO/GEANT simulations based on the known level schemes. Maxwellian averaged neutron capture cross sections were calculated for thermal energies between kT = 8 keV and 100 keV. Severe differences up to40% were found to the data of a recent evaluation based on existing experimental results. The new data allow for a much more reliable analysis of the important branching in the s-process synthesis path at 176Lu which can be interpreted as an s-process thermometer.

Informing neutron capture nucleosynthesis on short-lived nuclei with (d,p) reactions

NASA Astrophysics Data System (ADS)

Cizewski, Jolie A.; Ratkiewicz, Andrew; Escher, Jutta E.; Lepailleur, Alexandre; Pain, Steven D.; Potel, Gregory

2018-01-01

Neutron capture on unstable nuclei is important in understanding abundances in r-process nucleosynthesis. Previously, the non-elastic breakup of the deuteron in the (d,p) reaction has been shown to provide a neutron that can be captured by the nucleus and the gamma-ray decay of the subsequent compound nucleus can be modelled to predict the gamma-ray decay of the compound nucleus in the (n,γ) reaction. Preliminary results from the 95Mo(d,pγ) reaction in normal kinematics support the (d,pγ) reaction as a valid surrogate for neutron capture. The techniques to measure the (d,pγ) reaction in inverse kinematics have been developed.

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

PubMed

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

2014-06-01

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

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

PubMed

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

2014-06-01

A compact Liquid-Lithium Target (LiLiT) was built and tested with a high-power electron gun at Soreq Nuclear Research Center (SNRC). The target is intended to demonstrate liquid-lithium target capabilities to constitute an accelerator-based intense neutron source for Boron Neutron Capture Therapy (BNCT) in hospitals. The lithium target will produce neutrons through the (7)Li(p,n)(7)Be reaction and it will overcome the major problem of removing the thermal power >5kW generated by high-intensity proton beams, necessary for sufficient therapeutic neutron flux. In preliminary experiments liquid lithium was flown through the target loop and generated a stable jet on the concave supporting wall. Electron beam irradiation demonstrated that the liquid-lithium target can dissipate electron power densities of more than 4kW/cm(2) and volumetric power density around 2MW/cm(3) at a lithium flow of ~4m/s, while maintaining stable temperature and vacuum conditions. These power densities correspond to a narrow (σ=~2mm) 1.91MeV, 3mA proton beam. A high-intensity proton beam irradiation (1.91-2.5MeV, 2mA) is being commissioned at the SARAF (Soreq Applied Research Accelerator Facility) superconducting linear accelerator. In order to determine the conditions of LiLiT proton irradiation for BNCT and to tailor the neutron energy spectrum, a characterization of near threshold (~1.91MeV) (7)Li(p,n) neutrons is in progress based on Monte-Carlo (MCNP and Geant4) simulation and on low-intensity experiments with solid LiF targets. In-phantom dosimetry measurements are performed using special designed dosimeters based on CR-39 track detectors. © 2013 Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ana J. Molinari; Andrea Monti Hughes; Elisa M. Heber

2011-04-01

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

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

NASA Astrophysics Data System (ADS)

Lee, Taewoong; Lee, Hyounggun; Lee, Wonho

2015-10-01

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

Experimental evaluation of boron neutron capture therapy of human breast carcinoma implanted on nude mice

NASA Astrophysics Data System (ADS)

Bose, Satya Ranjan

2000-06-01

An in-pool small animal irradiation neutron tube (SAINT) facility was designed, constructed and installed at the University of Virginia Nuclear Research Reactor (UVAR). Thermal neutron flux profiles were measured by foil activation analysis (gold) and verified with DORT and MCNP computer code models. The gamma-ray absorbed dose in the neutron-gamma mixed field was determined from TLD measurements. The SAINT thermal neutron flux was used to investigate the well characterized human breast cancer cell line MCF-7B on both in-vitro samples and in- vivo animal subjects. Boronophenylalanine (BPA enriched in 95% 10B) was used as a neutron capturing agent. The in-vitro response of MCF-7B human breast carcinoma cells to BPA in a mixed field of neutron-gamma radiation or pure 60Co gamma radiation was investigated. The best result (lowest surviving fraction) was observed in cell cultures pre-incubated with BPA and given the neutron irradiation. The least effective treatment consisted of 60Co irradiation only. Immunologically deficient nude mice were inoculated subcutaneously with human breast cancer MCF-7B cells and estradiol pellets (to support tumor growth). The tumor volume in the mouse control group increased over time, as expected. The group of mice exposed only to neutron treatment exhibited initial tumor volume reduction lasting until 35 days following the treatment, followed by renewed tumor growth. Both groups given BPA plus neutron treatment showed continuous reduction in tumor volume over the 55-day observation period. The group given the higher BPA concentration showed the best tumor reduction response. The results on both in-vitro and in-vivo studies showed increased cell killing with BPA, substantiating the incorporation of BPA into the tumor or cell line. Therefore, BNCT may be a possible choice for the treatment of human breast carcinoma. However, prior to the initiation of any clinical studies, it is necessary to determine the therapeutic efficacy in a large

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

PubMed

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

2009-07-01

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

Spectroscopic Analyses of Neutron Capture Elements in Open Clusters

NASA Astrophysics Data System (ADS)

O'Connell, Julia E.

The evolution of elements as a function or age throughout the Milky Way disk provides strong constraints for galaxy evolution models, and on star formation epochs. In an effort to provide such constraints, we conducted an investigation into r- and s-process elemental abundances for a large sample of open clusters as part of an optical follow-up to the SDSS-III/APOGEE-1 near infrared survey. To obtain data for neutron capture abundance analysis, we conducted a long-term observing campaign spanning three years (2013-2016) using the McDonald Observatory Otto Struve 2.1-meter telescope and Sandiford Cass Echelle Spectrograph (SES, R(lambda/Deltalambda) ˜60,000). The SES provides a wavelength range of ˜1400 A, making it uniquely suited to investigate a number of other important chemical abundances as well as the neutron capture elements. For this study, we derive abundances for 18 elements covering four nucleosynthetic families- light, iron-peak, neutron capture and alpha-elements- for ˜30 open clusters within 6 kpc of the Sun with ages ranging from ˜80 Myr to ˜10 Gyr. Both equivalent width (EW) measurements and spectral synthesis methods were employed to derive abundances for all elements. Initial estimates for model stellar atmospheres- effective temperature and surface gravity- were provided by the APOGEE data set, and then re-derived for our optical spectra by removing abundance trends as a function of excitation potential and reduced width log(EW/lambda). With the exception of Ba II and Zr I, abundance analyses for all neutron capture elements were performed by generating synthetic spectra from the new stellar parameters. In order to remove molecular contamination, or blending from nearby atomic features, the synthetic spectra were modeled by a best-fit Gaussian to the observed data. Nd II shows a slight enhancement in all cluster stars, while other neutron capture elements follow solar abundance trends. Ba II shows a large cluster-to-cluster abundance spread

Assessment of biological effectiveness of boron neutron capture therapy in primary and metastatic melanoma cell lines.

PubMed

Rossini, Andrés E; Dagrosa, Maria A; Portu, Agustina; Saint Martin, Giselle; Thorp, Silvia; Casal, Mariana; Navarro, Aimé; Juvenal, Guillermo J; Pisarev, Mario A

2015-01-01

In order to optimize the effectiveness of Boron Neutron Capture Therapy (BNCT), Relative Biological Effectiveness (RBE) and Compound Biological Effectiveness (CBE) were determined in two human melanoma cell lines, M8 and Mel-J cells, using the amino acid p-boronophenylalanine (BPA) as boron carrier. The effects of BNCT on the primary amelanotic cell line M8 and on the metastatic pigmented melanoma cell line Mel-J were studied using colony formation assay. The RBE values were determined using both a gamma ray source, and the neutron beam from the Nuclear Reactor of the National Atomic Energy Commission (RA-3). For the determination of the RBE, cells were irradiated with increasing doses of both sources, between 1 and 8 Gy; and for the determination of CBE factors, the cells were pre-incubated with BPA before irradiation. Afterwards, the cell surviving fraction (SF) was determined for each treatment. Marked differences were observed between both cell lines. Mel-J cells were more radioresistant than the M8 cell line. The clonogenic assays showed that for a SF of 1%, the RBE values were 1.3 for M8 cells and 1.5 for Mel-J cells. Similarly, the CBE values for a 1% SF were 2.1 for M8 and 3 for Mel-J cell lines. For the endpoint of 0.1% of SF the RBE values obtained were 1.2 for M8 and 1.4 for Mel-J cells. Finally, CBE values calculated for a 0.1% were 2 and 2.6 for M8 and Mel-J cell lines respectively. In order to estimate the uptake of the non-radioactive isotope Boron 10 ((10)B), a neutron induced autoradiographic technique was performed showing discrepancies in (10)B uptake between both cell lines. These obtained in vitro results are the first effectiveness factors determined for human melanoma at the RA-3 nuclear reactor and show that BNCT dosimetry planning for patients could be successfully performed using these new factors.

Study on the keV neutron capture reaction in 56Fe and 57Fe

NASA Astrophysics Data System (ADS)

Wang, Taofeng; Lee, Manwoo; Kim, Guinyun; Ro, Tae-Ik; Kang, Yeong-Rok; Igashira, Masayuki; Katabuchi, Tatsuya

2014-03-01

The neutron capture cross-sections and the radiative capture gamma-ray spectra from the broad resonances of 56Fe and 57Fe in the neutron energy range from 10 to 90keV and 550keV have been measured with an anti-Compton NaI(Tl) detector. Pulsed keV neutrons were produced from the 7Li 7Be reaction by bombarding the lithium target with the 1.5ns bunched proton beam from the 3MV Pelletron accelerator. The incident neutron spectrum on a capture sample was measured by means of a time-of-flight (TOF) method with a 6Li -glass detector. The number of weighted capture counts of the iron or gold sample was obtained by applying a pulse height weighting technique to the corresponding capture gamma-ray pulse height spectrum. The neutron capture gamma-ray spectra were obtained by unfolding the observed capture gamma-ray pulse height spectra. To achieve further understanding on the mechanism of neutron radiative capture reaction and study on physics models, theoretical calculations of the -ray spectra for 56Fe and 57Fe with the POD program have been performed by applying the Hauser-Feshbach statistical model. The dominant ingredients to perform the statistical calculation were the Optical Model Potential (OMP), the level densities described by the Mengoni-Nakajima approach, and the -ray transmission coefficients described by -ray strength functions. The comparison of the theoretical calculations, performed only for the 550keV point, show a good agreement with the present experimental results.

Estimation of relative biological effectiveness for boron neutron capture therapy using the PHITS code coupled with a microdosimetric kinetic model.

PubMed

Horiguchi, Hironori; Sato, Tatsuhiko; Kumada, Hiroaki; Yamamoto, Tetsuya; Sakae, Takeji

2015-03-01

The absorbed doses deposited by boron neutron capture therapy (BNCT) can be categorized into four components: α and (7)Li particles from the (10)B(n, α)(7)Li reaction, 0.54-MeV protons from the (14)N(n, p)(14)C reaction, the recoiled protons from the (1)H(n, n) (1)H reaction, and photons from the neutron beam and (1)H(n, γ)(2)H reaction. For evaluating the irradiation effect in tumors and the surrounding normal tissues in BNCT, it is of great importance to estimate the relative biological effectiveness (RBE) for each dose component in the same framework. We have, therefore, established a new method for estimating the RBE of all BNCT dose components on the basis of the microdosimetric kinetic model. This method employs the probability density of lineal energy, y, in a subcellular structure as the index for expressing RBE, which can be calculated using the microdosimetric function implemented in the particle transport simulation code (PHITS). The accuracy of this method was tested by comparing the calculated RBE values with corresponding measured data in a water phantom irradiated with an epithermal neutron beam. The calculation technique developed in this study will be useful for biological dose estimation in treatment planning for BNCT. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Proton Neutron Gamma-X Detection (PNGXD): An introduction to contrast agent detection during proton therapy via prompt gamma neutron activation

NASA Astrophysics Data System (ADS)

Gräfe, James L.

2017-09-01

Proton therapy is an alternative external beam cancer treatment modality to the conventional linear accelerator-based X-ray radiotherapy. An inherent by-product of proton-nuclear interactions is the production of secondary neutrons. These neutrons have long been thought of as a secondary contaminant, nuisance, and source of secondary cancer risk. In this paper, a method is proposed to use these neutrons to identify and localize the presence of the tumor through neutron capture reactions with the gadolinium-based MRI contrast agent. This could provide better confidence in tumor targeting by acting as an additional quality assurance tool of tumor position during treatment. This effectively results in a neutron induced nuclear medicine scan. Gadolinium (Gd), is an ideal candidate for this novel nuclear contrast imaging procedure due to its unique nuclear properties and its widespread use as a contrast agent in MRI. Gd has one of the largest thermal neutron capture cross sections of all the stable nuclides, and the gadolinium-based contrast agents localize in leaky tissues and tumors. Initial characteristics of this novel concept were explored using the Monte Carlo code MCNP6. The number of neutron capture reactions per Gy of proton dose was found to be approximately 50,000 neutron captures/Gy, for a 8 cm3 tumor containing 300 ppm Gd at 8 cm depth with a simple simulation designed to represent the active delivery method. Using the passive method it is estimated that this number can be up to an order of magnitude higher. The thermal neutron distribution was found to not be localized within the spread out Bragg peak (SOBP) for this geometrical configuration and therefore would not allow for the identification of a geometric miss of the tumor by the proton SOBP. However, this potential method combined with nuclear medicine imaging and fused with online CBCT and prior MRI or CT imaging could help to identify tumor position during treatment. More computational and

Neutron Capture Energies for Flux Normalization and Approximate Model for Gamma-Smeared Power

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Kang Seog; Clarno, Kevin T.; Liu, Yuxuan

The Consortium for Advanced Simulation of Light Water Reactors (CASL) Virtual Environment for Reactor Applications (VERA) neutronics simulator MPACT has used a single recoverable fission energy for each fissionable nuclide assuming that all recoverable energies come only from fission reaction, for which capture energy is merged with fission energy. This approach includes approximations and requires improvement by separating capture energy from the merged effective recoverable energy. This report documents the procedure to generate recoverable neutron capture energies and the development of a program called CapKappa to generate capture energies. Recoverable neutron capture energies have been generated by using CapKappa withmore » the evaluated nuclear data file (ENDF)/B-7.0 and 7.1 cross section and decay libraries. The new capture kappas were compared to the current SCALE-6.2 and the CASMO-5 capture kappas. These new capture kappas have been incorporated into the Simplified AMPX 51- and 252-group libraries, and they can be used for the AMPX multigroup (MG) libraries and the SCALE code package. The CASL VERA neutronics simulator MPACT does not include a gamma transport capability, which limits it to explicitly estimating local energy deposition from fission, neutron, and gamma slowing down and capture. Since the mean free path of gamma rays is typically much longer than that for the neutron, and the total gamma energy is about 10% to the total energy, the gamma-smeared power distribution is different from the fission power distribution. Explicit local energy deposition through neutron and gamma transport calculation is significantly important in multi-physics whole core simulation with thermal-hydraulic feedback. Therefore, the gamma transport capability should be incorporated into the CASL neutronics simulator MPACT. However, this task will be timeconsuming in developing the neutron induced gamma production and gamma cross section libraries. This study is to

Understanding the potentiality of accelerator based-boron neutron capture therapy for osteosarcoma: dosimetry assessment based on the reported clinical experience.

PubMed

Bortolussi, Silva; Postuma, Ian; Protti, Nicoletta; Provenzano, Lucas; Ferrari, Cinzia; Cansolino, Laura; Dionigi, Paolo; Galasso, Olimpio; Gasparini, Giorgio; Altieri, Saverio; Miyatake, Shin-Ichi; González, Sara J

2017-08-15

Osteosarcoma is the most frequent primary malignant bone tumour, and its incidence is higher in children and adolescents, for whom it represents more than 10% of solid cancers. Despite the introduction of adjuvant and neo-adjuvant chemotherapy that markedly increased the success rate in the treatment, aggressive surgery is still needed and a considerable percentage of patients do not survive due to recurrences or early metastases. Boron Neutron Capture Therapy (BNCT), an experimental radiotherapy, was investigated as a treatment that could allow a less aggressive surgery by killing infiltrated tumour cells in the surrounding healthy tissues. BNCT requires an intense neutron beam to ensure irradiation times of the order of 1 h. In Italy, a Radio Frequency Quadrupole (RFQ) proton accelerator has been designed and constructed for BNCT, and a suitable neutron spectrum was tailored by means of Monte Carlo calculations. This paper explores the feasibility of BNCT to treat osteosarcoma using this neutron source based on accelerator. The therapeutic efficacy of BNCT was analysed evaluating the dose distribution obtained in a clinical case of femur osteosarcoma. Mixed field dosimetry was assessed with two different formalisms whose parameters were specifically derived from radiobiological experiments involving in vitro UMR-106 osteosarcoma cell survival assays and boron concentration assessments in an animal model of osteosarcoma. A clinical case of skull osteosarcoma treated with BNCT in Japan was re-evaluated from the point of view of dose calculation and used as a reference for comparison. The results in the case of femur osteosarcoma show that the RFQ beam would ensure a suitable tumour dose painting in a total irradiation time of less than an hour. Comparing the dosimetry between the analysed case and the treated patient in Japan it turns out that doses obtained in the femur tumour are at least as good as the ones delivered in the skull osteosarcoma. The same is

Neutron Capture Rates and the r-Process Abundance Pattern in Shocked Neutrino-Driven Winds

NASA Astrophysics Data System (ADS)

Barringer, Daniel; Surman, Rebecca

2009-10-01

The r-process is an important process in nucleosynthesis in which nuclei will undergo rapid neutron captures. Models of the r-process require nuclear data such as neutron capture rates for thousands of individual nuclei, many of which lie far from stability. Among the potential sites for the r-process, and the one that we investigate, is the shocked neutrino-driven wind in core-collapse supernovae. Here we examine the importance of the neutron capture rates of specific, individual nuclei in the second r-process abundance peak occurring at A ˜ 130 for a range of parameterized neutrino-driven wind trajectories. Of specific interest are the nuclei whose capture rates affect the abundances of nuclei outside of the A ˜ 130 peak. We found that increasing the neutron capture rate for a number of nuclei including ^135In, ^132Sn, ^133Sb, ^137Sb, and ^136Te can produce changes in the resulting abundance pattern of up to 13%.

Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases.

PubMed

Miyatake, Shin-Ichi; Furuse, Motomasa; Kawabata, Shinji; Maruyama, Takashi; Kumabe, Toshihiro; Kuroiwa, Toshihiko; Ono, Koji

2013-06-01

Bevacizumab, an anti-vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas. Two recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression. The first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No tumor progression was observed 8 months after BNCT. Bevacizumab showed marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas.

Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

PubMed Central

Kueffer, Peter J.; Maitz, Charles A.; Khan, Aslam A.; Schuster, Seth A.; Shlyakhtina, Natalia I.; Jalisatgi, Satish S.; Brockman, John D.; Nigg, David W.; Hawthorne, M. Frederick

2013-01-01

The application of boron neutron capture therapy (BNCT) following liposomal delivery of a 10B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2′-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 µg/g tumor at 54 h—with tumor/blood boron ratios being greatest at 96 h (5.68:1; 43 µg boron/g tumor)—following the initial injection. For BNCT experiments, tumor-bearing mice were irradiated 54 h after the initial injection for 30 min with thermal neutrons, resulting in a total fluence of 1.6 × 1012 neutrons per cm2 (±7%). Significant suppression of tumor growth was observed in mice given BNCT vs. control mice (only 424% increase in tumor volume at 14 d post irradiation vs. 1551% in untreated controls). In a separate experiment in which mice were given a second injection/irradiation treatment 7 d after the first, the tumor growth was vastly diminished (186% tumor volume increase at 14 d). A similar response was obtained for mice irradiated for 60 min (169% increase at 14 d), suggesting that neutron fluence was the limiting factor controlling BNCT efficacy in this study. PMID:23536304

Boron neutron capture therapy (BNCT) for the treatment of liver metastases: biodistribution studies of boron compounds in an experimental model.

PubMed

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

2011-03-01

We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of (10)B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na(2)(10)B(10)H(10)), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3. © Springer-Verlag 2010

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

PubMed

Monti Hughes, A M; Pozzi, E C C; Thorp, S; Garabalino, M A; Farías, R O; González, 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

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. Groups of cancerized hamsters were locally exposed to single or double (2 or 4 weeks apart) applications of BNCT at different dose levels, mediated by the boron compounds boronophenylalanine (BPA) or BPA and decahydrodecaborate (GB-10) administered jointly. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumour development from field-cancerized tissue and mucositis were followed for 8 months. A double application (4 weeks apart) of BNCT mediated by GB-10+ BPA at a total dose of 10 Gy in two 5-Gy doses rendered the best therapeutic advantage (63-100% inhibition of tumour development from field-cancerized tissue), minimizing dose-limiting mucositis. BNCT can be optimized for the integral treatment for head and neck cancer, considering the implications for field-cancerized tissue. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, S; Suh, T; Yoon, D

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).more » 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.« less

New measurement of θ 13 via neutron capture on hydrogen at Daya Bay

DOE PAGES

F. P. An

2016-04-21

This article reports an improved independent measurement of neutrino mixing angle θ 13 at the Daya Bay Reactor Neutrino Experiment. Electron antineutrinos were identified by inverse β-decays with the emitted neutron captured by hydrogen, yielding a data set with principally distinct uncertainties from that with neutrons captured by gadolinium. With the final two of eight antineutrino detectors installed, this study used 621 days of data including the previously reported 217-day data set with six detectors. The dominant statistical uncertainty was reduced by 49%. Intensive studies of the cosmogenic muon-induced 9Li and fast neutron backgrounds and the neutron-capture energy selection efficiency,more » resulted in a reduction of the systematic uncertainty by 26%. The deficit in the detected number of antineutrinos at the far detectors relative to the expected number based on the near detectors yielded sin 22θ 13 = 0.071 ± 0.011 in the three-neutrino-oscillation framework. As a result, the combination of this result with the gadolinium-capture result is also reported.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Theroine, C.; Ebran, A.; Meot, V.

2013-06-10

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

THE INTERMEDIATE NEUTRON-CAPTURE PROCESS AND CARBON-ENHANCED METAL-POOR STARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hampel, Melanie; Stancliffe, Richard J.; Lugaro, Maria

Carbon-enhanced metal-poor (CEMP) stars in the Galactic Halo display enrichments in heavy elements associated with either the s (slow) or the r (rapid) neutron-capture process (e.g., barium and europium, respectively), and in some cases they display evidence of both. The abundance patterns of these CEMP- s / r stars, which show both Ba and Eu enrichment, are particularly puzzling, since the s and the r processes require neutron densities that are more than ten orders of magnitude apart and, hence, are thought to occur in very different stellar sites with very different physical conditions. We investigate whether the abundance patternsmore » of CEMP- s / r stars can arise from the nucleosynthesis of the intermediate neutron-capture process (the i process), which is characterized by neutron densities between those of the s and the r processes. Using nuclear network calculations, we study neutron capture nucleosynthesis at different constant neutron densities n ranging from 10{sup 7}–10{sup 15} cm{sup -3}. With respect to the classical s process resulting from neutron densities on the lowest side of this range, neutron densities on the highest side result in abundance patterns, which show an increased production of heavy s -process and r -process elements, but similar abundances of the light s -process elements. Such high values of n may occur in the thermal pulses of asymptotic giant branch stars due to proton ingestion episodes. Comparison to the surface abundances of 20 CEMP- s / r stars shows that our modeled i -process abundances successfully reproduce observed abundance patterns, which could not be previously explained by s -process nucleosynthesis. Because the i -process models fit the abundances of CEMP- s / r stars so well, we propose that this class should be renamed as CEMP- i .« less

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

PubMed Central

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

2014-01-01

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

Thermal neutron capture cross section for 56Fe(n ,γ )

NASA Astrophysics Data System (ADS)

Firestone, R. B.; Belgya, T.; Krtička, M.; Bečvář, F.; Szentmikloṡi, L.; Tomandl, I.

2017-01-01

The 56Fe(n ,γ ) thermal neutron capture cross section and the 57Fe level scheme populated by this reaction have been investigated in this work. Singles γ -ray spectra were measured with an isotopically enriched 56Fe target using the guided cold neutron beam at the Budapest Reactor, and γ γ -coincidence data were measured with a natural Fe target at the LWR-15 research reactor in Řež, Czech Republic. A detailed level scheme consisting of 448 γ rays populating/depopulating 97 levels and the capture state in 57Fe has been constructed, and ≈99 % of the total transition intensity has been placed. The transition probability of the 352-keV γ ray was determined to be Pγ(352 ) =11.90 ±0.07 per 100 neutron captures. The 57Fe level scheme is substantially revised from earlier work and ≈33 previously assigned levels could not be confirmed while a comparable number of new levels were added. The 57Feγ -ray cross sections were internally calibrated with respect to 1H and 32Sγ -ray cross section standards using iron(III) acetylacetonate (C15H21FeO6) and iron pyrite (FeS2) targets. The thermal neutron cross section for production of the 352-keV γ -ray cross section was determined to be σγ(352 ) =0.2849 ±0.015 b. The total 56Fe(n ,γ ) thermal radiative neutron cross section is derived from the 352-keV γ -ray cross section and transition probability as σ0=2.394 ±0.019 b. A least-squares fit of the γ rays to the level scheme gives the 57Fe neutron separation energy Sn=7646.183 ±0.018 keV.

Assessment of 10B concentration in boron neutron capture therapy: potential of image-guided therapy using 18FBPA PET.

PubMed

Shimosegawa, Eku; Isohashi, Kayako; Naka, Sadahiro; Horitsugi, Genki; Hatazawa, Jun

2016-12-01

In boron neutron capture therapy (BNCT) for cancer, the accurate estimation of 10 B tissue concentrations, especially in neighboring normal organs, is important to avoid adverse effects. The 10 B concentration in normal organs after loading with 10 B, however, has not been established in humans. In this study, we performed 4-borono-2-[ 18 F]-fluoro-phenylalanine ( 18 FBPA) PET in healthy volunteers and estimated the chronological changes in the 10 B concentrations of normal organs. In 6 healthy volunteers, whole-body 18 FBPA PET scans were repeated 7 times during 1 h, and the mean 18 FBPA distributions of 13 organs were measured. Based on the 18 FBPA PET data, we then estimated the changes in the 10 B concentrations of the organs when the injection of a therapeutic dose of 10 BPA-fructose complex ( 10 BPA-fr; 30 g, 500 mg/kg body weight) was assumed. The maximum mean 18 FBPA concentrations were reached at 2-6 min after injection in all the organs except the brain and urinary bladder. The mean 18 FBPA concentration in normal brain plateaued at 24 min after injection. When the injection of a therapeutic dose of 10 BPA-fr was assumed, the estimated mean 10 B concentration in the kidney increased to 126.1 ± 24.2 ppm at 3 min after injection and then rapidly decreased to 30.9 ± 7.4 ppm at 53 min. The estimated mean 10 B concentration in the bladder gradually increased and reached 383.6 ± 214.7 ppm at 51 min. The mean 10 B concentration in the brain was estimated to be 7.6 ± 1.5 ppm at 57 min. 18 FBPA PET has a potential to estimate 10 B concentration of normal organs before neutron irradiation of BNCT when several assumptions are validated in the future studies.

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

NASA Astrophysics Data System (ADS)

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

2006-03-01

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

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

PubMed

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

2006-03-07

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

Modern alchemy: Fred Hoyle and element building by neutron capture

NASA Astrophysics Data System (ADS)

Burbidge, E. Margaret

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

Experimental and Theoretical Understanding of Neutron Capture on Uranium Isotopes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ullmann, John Leonard

2017-09-21

Neutron capture cross sections on uranium isotopes are important quantities needed to model nuclear explosion performance, nuclear reactor design, nuclear test diagnostics, and nuclear forensics. It has been difficult to calculate capture accurately, and factors of 2 or more be- tween calculation and measurements are not uncommon, although normalization to measurements of the average capture width and nuclear level density can improve the result. The calculations of capture for 233,235,237,239U are further complicated by the need to accurately include the fission channel.

Measurement of keV-neutron capture cross sections and capture gamma-ray spectra of Cs-133 and I-127

NASA Astrophysics Data System (ADS)

Umezawa, Seigo; Igashira, Masayuki; Katabuchi, Tatuya; Dominic, Moraru; Yanagida, Shotaro; Okamiya, Tomohiro

2017-09-01

The neutron capture cross sections and the capture gamma-ray spectra of 127I and 133Cs at incident neutron energies from 15 to 100 keV have been measured by the time-of-flight method. Capture gamma-rays were detected with an anti-Compton NaI(Tl) spectrometer, and the pulse-height weighting technique was applied to derive capture yields. The capture cross sections of 127I and 133Cs were determined using the standard capture cross section of 197Au. The total errors of the cross sections were 3.8-5.1%. The obtained cross sections were compared with evaluated values in JENDL-4.0 and ENDF/B-VII.1. For 127I, the energy dependence is different between the present results and the evaluations. For 133Cs, the evaluated values in JENDL-4.0 agree with the present results but the evaluated values in ENDF/B-VII.1 are smaller than the present results by 14%-18%. The capture gamma-ray spectra of 133Cs and 127I were derived by unfolding the pulse height spectra with detector response functions.

Preparation of iridium targets by electrodeposition for neutron capture cross section measurements

DOE PAGES

Bond, Evelyn M.; Moody, W. Allen; Arnold, Charles; ...

2016-03-01

Here, the preparation of 191Ir and 193Ir electrodeposits for neutron capture cross-section measurements at the detector for advanced neutron capture experiments located at the at Los Alamos Neutron Science Center is described. The electrodeposition of iridium in the desired thickness of 0.4–1 mg/cm 2 is challenging. Better yields and thicknesses were obtained using electrodeposition from isopropyl alcohol solutions than from ammonium sulfate solutions. 191Ir and 193Ir targets were initially prepared using the standard single-sided electrodeposition cell. Iridium electrodepositions using a double-sided electrodeposition cell were developed and were optimized, resulting in thick, uniform iridium deposits. LA UR 15-22475.

Radiative neutron capture cross section from 236U

NASA Astrophysics Data System (ADS)

Baramsai, B.; Jandel, M.; Bredeweg, T. A.; Bond, E. M.; Roman, A. R.; Rusev, G.; Walker, C. L.; Couture, A.; Mosby, S.; O'Donnell, J. M.; Ullmann, J. L.; Kawano, T.

2017-08-01

The 236U(n ,γ ) reaction cross section has been measured for the incident neutron energy range from 10 eV to 800 keV by using the Detector for Advanced Neutron Capture Experiments (DANCE) γ -ray calorimeter at the Los Alamos Neutron Science Center. The cross section was determined with the ratio method, which is a technique that uses the 235U(n ,f ) reaction as a reference. The results of the experiment are reported in the resolved and unresolved resonance energy regions. Individual neutron resonance parameters were obtained below 1 keV incident energy by using the R -matrix code sammy. The cross section in the unresolved resonance region is determined with improved experimental uncertainty. It agrees with both ENDF/B-VII.1 and JEFF-3.2 nuclear data libraries. The results above 10 keV agree better with the JEFF-3.2 library.

Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases

PubMed Central

Miyatake, Shin-Ichi; Furuse, Motomasa; Kawabata, Shinji; Maruyama, Takashi; Kumabe, Toshihiro; Kuroiwa, Toshihiko; Ono, Koji

2013-01-01

Background Bevacizumab, an anti–vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas. Methods Two recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression. Results The first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No tumor progression was observed 8 months after BNCT. Conclusions Bevacizumab showed marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas. PMID:23460324

Neutron capture and stellar synthesis of heavy elements.

PubMed

Gibbons, J H; Macklin, R L

1967-05-26

The neutron buildup processes of heavy-element synthesis in stars have left us a number of tantalizing nuclear clues to the early history of solarsystem material. Considerable illumination of our past history has been achieved through studying the correlations between abundance and neutroncapture cross section. Measurement of these cross sections required the development of new techniques for measuring time of flight of pulsed neutron beams. A clear conclusion is that many of our heavy elements were produced inside stars, which can be thought of as giant fast reactors. Extensions of these capture studies have given a clearer picture of additional. violent processes which produced some heavy elements, particularly thorium and uranium. In addition, the correlations have been used for obtaining an independent measure of the time that has elapsed since the solar-system material was synthesized. Finally, data on capture cross section relative to abundance will enable us to determine rather accurately the solar-system abundances of gaseous, volatile, and highly segregated elements.

Statistical Features of the Thermal Neutron Capture Cross Sections

DOE PAGES

Hussein, M. S.; Carlson, B. V.; Kerman, A. K.

2016-02-01

In this paper, we discuss the existence of huge thermal neutron capture cross sections in several nuclei. The values of the cross sections are several orders of magnitude bigger than expected at these very low energies. We lend support to the idea that this phenomenon is random in nature and is similar to what we have learned from the study of parity violation in the actinide region. The idea of statistical doorways is advanced as a unified concept in the delineation of large numbers in the nuclear world. The average number of maxima per unit mass, < n A >more » in the capture cross section is calculated and related to the underlying cross section correlation function and found to be < n A > = 3/(π√2γ A), where γ A is a characteristic mass correlation width which designates the degree of remnant coherence in the system. Finally, we trace this coherence to nucleosynthesis which produced the nuclei whose neutron capture cross sections are considered here.« less

Statistical Features of the Thermal Neutron Capture Cross Sections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hussein, M. S.; Carlson, B. V.; Kerman, A. K.

In this paper, we discuss the existence of huge thermal neutron capture cross sections in several nuclei. The values of the cross sections are several orders of magnitude bigger than expected at these very low energies. We lend support to the idea that this phenomenon is random in nature and is similar to what we have learned from the study of parity violation in the actinide region. The idea of statistical doorways is advanced as a unified concept in the delineation of large numbers in the nuclear world. The average number of maxima per unit mass, < n A >more » in the capture cross section is calculated and related to the underlying cross section correlation function and found to be < n A > = 3/(π√2γ A), where γ A is a characteristic mass correlation width which designates the degree of remnant coherence in the system. Finally, we trace this coherence to nucleosynthesis which produced the nuclei whose neutron capture cross sections are considered here.« less

Evaluating the Usefulness of a Novel 10B-Carrier Conjugated With Cyclic RGD Peptide in Boron Neutron Capture Therapy

PubMed Central

Masunaga, Shin-ichiro; Kimura, Sadaaki; Harada, Tomohiro; Okuda, Kensuke; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Maruhashi, Akira; Nagasawa, Hideko; Ono, Koji

2012-01-01

Background To evaluate the usefulness of a novel 10B-carrier conjugated with an integrin-binding cyclic RGD peptide (GPU-201) in boron neutron capture therapy (BNCT). Methods GPU-201 was synthesized from integrin-binding Arg-Gly-Asp (RGD) consensus sequence of matrix proteins and a 10B cluster 1, 2-dicarba-closo-dodecaborane-10B. Mercaptododecaborate-10B (BSH) dissolved in physiological saline and BSH and GPU-201 dissolved with cyclodextrin (CD) as a solubilizing and dispersing agent were intraperitoneally administered to SCC VII tumor-bearing mice. Then, the 10B concentrations in the tumors and normal tissues were measured by γ-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2’-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, then treated with GPU-201, BSH-CD, or BSH. Immediately after reactor neutron beam or γ-ray irradiation, during which intratumor 10B concentrations were kept at levels similar to each other, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (= P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. Results The 10B from BSH was washed away rapidly in all these tissues and the retention of 10B from BSH-CD and GPU-201 was similar except in blood where the 10B concentration from GPU-201 was higher for longer. GPU-201 showed a significantly stronger radio-sensitizing effect under neutron beam irradiation on both total and Q cell populations than any other 10B-carrier. Conclusion A novel 10B-carrier conjugated with an integrin-binding RGD peptide (GPU-201) that sensitized tumor cells more markedly than conventional 10B-carriers may be a promising candidate for use in BNCT. However, its toxicity needs to be tested further. PMID:29147290

NEW NEUTRON-CAPTURE MEASUREMENTS IN 23 OPEN CLUSTERS. I. THE r -PROCESS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Overbeek, Jamie C.; Friel, Eileen D.; Jacobson, Heather R., E-mail: joverbee@indiana.edu

2016-06-20

Neutron-capture elements, those with Z > 35, are the least well understood in terms of nucleosynthesis and formation environments. The rapid neutron-capture, or r -process, elements are formed in the environments and/or remnants of massive stars, while the slow neutron-capture, or s -process, elements are primarily formed in low-mass AGB stars. These elements can provide much information about Galactic star formation and enrichment, but observational data are limited. We have assembled a sample of 68 stars in 23 open clusters that we use to probe abundance trends for six neutron-capture elements (Eu, Gd, Dy, Mo, Pr, and Nd) with clustermore » age and location in the disk of the Galaxy. In order to keep our analysis as homogeneous as possible, we use an automated synthesis fitting program, which also enables us to measure multiple (3–10) lines for each element. We find that the pure r -process elements (Eu, Gd, and Dy) have positive trends with increasing cluster age, while the mixed r - and s -process elements (Mo, Pr, and Nd) have insignificant trends consistent with zero. Pr, Nd, Eu, Gd, and Dy have similar, slight (although mostly statistically significant) gradients of ∼0.04 dex kpc{sup −1}. The mixed elements also appear to have nonlinear relationships with R {sub GC}.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ullmann, J. L.; Haight, Robert C.; Hunt, L. F.

2002-01-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari

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 studiesmore » 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.« less

Thermal-neutron capture gamma-rays. Volume 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuli, J.K.

1997-05-01

The energy and photon intensity of gamma rays as seen in thermal-neutron capture are presented ordered by Z, A of target nuclei. All gamma-rays with intensity of {ge}2% of the strongest transition are included. The strongest transition is indicated in each case. Where the target nuclide mass number is indicated as nat the natural target was used. The gamma energies given are in keV. The gamma intensities given are relative to 100 for the strongest transition. All data for A > 44 are taken from Evaluated Nuclear Structure Data File (4/97), a computer file of evaluated nuclear structure data maintainedmore » by the National Nuclear Data Center, Brookhaven National Laboratory, on behalf of the Nuclear Structure and Decay and Decay Data network, coordinated by the International Atomic Energy Agency, Vienna. These data are published in Nuclear Data Sheets, Academic Press, San Diego, CA. The data for A {le} 44 is taken from ``Prompt Gamma Rays from Thermal-Neutron Capture,`` M.A. Lone, R.A. Leavitt, D.A. Harrison, Atomic Data and Nuclear Data Tables 26, 511 (1981).« less

Thermal-neutron capture gamma-rays. Volume 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuli, J.K.

1997-05-01

The energy and photon intensity of gamma rays as seen in thermal-neutron capture are presented in ascending order of gamma energy. All those gamma-rays with intensity of {ge} 2% of the strongest transition are included. The two strongest transitions seen for the target nuclide are indicated in each case. Where the target nuclide mass number is indicated as nat the natural target was used. The gamma energies given are in keV. The gamma intensities given are relative to 100 for the strongest transition. All data for A > 44 are taken from Evaluated Nuclear Structure Data File (4/97), a computermore » file of evaluated nuclear structure data maintained by the National Nuclear Data Center, Brookhaven National Laboratory, on behalf of the Nuclear Structure and Decay and Decay Data network, coordinated by the International Atomic Energy Agency, Vienna. These data are published in Nuclear Data Sheets, Academic Press, San Diego, CA. The data for A {le} 44 is taken from ``Prompt Gamma Rays from Thermal-Neutron Capture,`` M.A. Lone, R.A. Leavitt, D.A. Harrison, Atomic Data and Nuclear Data Tables 26, 511 (1981).« less

L-Phenylalanine preloading reduces the (10)B(n, α)(7)Li dose to the normal brain by inhibiting the uptake of boronophenylalanine in boron neutron capture therapy for brain tumours.

PubMed

Watanabe, Tsubasa; Tanaka, Hiroki; Fukutani, Satoshi; Suzuki, Minoru; Hiraoka, Masahiro; Ono, Koji

2016-01-01

Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. Previously, high doses of one of the boron compounds used for BNCT, L-BPA, were found to reduce the boron-derived irradiation dose to the central nervous system. However, injection with a high dose of L-BPA is not feasible in clinical settings. We aimed to find an alternative method to improve the therapeutic efficacy of this therapy. We examined the effects of oral preloading with various analogues of L-BPA in a xenograft tumour model and found that high-dose L-phenylalanine reduced the accumulation of L-BPA in the normal brain relative to tumour tissue. As a result, the maximum irradiation dose in the normal brain was 19.2% lower in the L-phenylalanine group relative to the control group. This study provides a simple strategy to improve the therapeutic efficacy of conventional boron compounds for BNCT for brain tumours and the possibility to widen the indication of BNCT to various kinds of other tumours. Copyright © 2015. Published by Elsevier Ireland Ltd.

Quantitative bioimaging of p-boronophenylalanine in thin liver tissue sections as a tool for treatment planning in boron neutron capture therapy.

PubMed

Reifschneider, Olga; Schütz, Christian L; Brochhausen, Christoph; Hampel, Gabriele; Ross, Tobias; Sperling, Michael; Karst, Uwe

2015-03-01

An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of 10B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of 10B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of 10B in cancerous and healthy tissue was carried out. Additionally, the distribution of 11B was investigated, providing 10B enrichment in the investigated tissues. Quantitative imaging of 10B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT.

Performance verification of an epithermal neutron flux monitor using accelerator-based BNCT neutron sources

NASA Astrophysics Data System (ADS)

Guan, X.; Murata, I.; Wang, T.

2017-09-01

The performance of an epithermal neutron flux monitor developed for boron neutron capture therapy (BNCT) is verified by Monte Carlo simulations using accelerator-based neutron sources (ABNSs). The results indicate that the developed epithermal neutron flux monitor works well and it can be efficiently used in practical applications to measure the epithermal neutron fluxes of ABNSs in a high accuracy.

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

PubMed

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

Neutron radiative capture methods for surface elemental analysis

USGS Publications Warehouse

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

1970-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2015-07-01

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

Absolute measurement of the 242Pu neutron-capture cross section

DOE PAGES

Buckner, M. Q.; Wu, C. Y.; Henderson, R. A.; ...

2016-04-21

Here, the absolute neutron-capture cross section of 242Pu was measured at the Los Alamos Neutron Science Center using the Detector for Advanced Neutron-Capture Experiments array along with a compact parallel-plate avalanche counter for fission-fragment detection. The first direct measurement of the 242Pu(n,γ) cross section was made over the incident neutron energy range from thermal to ≈ 6 keV, and the absolute scale of the (n,γ) cross section was set according to the known 239Pu(n,f) resonance at E n,R = 7.83 eV. This was accomplished by adding a small quantity of 239Pu to the 242Pu sample. The relative scale of themore » cross section, with a range of four orders of magnitude, was determined for incident neutron energies from thermal to ≈ 40 keV. Our data, in general, are in agreement with previous measurements and those reported in ENDF/B-VII.1; the 242Pu(n,γ) cross section at the E n,R = 2.68 eV resonance is within 2.4% of the evaluated value. However, discrepancies exist at higher energies; our data are ≈30% lower than the evaluated data at E n ≈ 1 keV and are approximately 2σ away from the previous measurement at E n ≈ 20 keV.« less

Diversity of abundance patterns of neutron-capture elements in very metal-poor stars

NASA Astrophysics Data System (ADS)

Aoki, Misa; Aoki, Wako; Ishimaru, Yuhri; Wanajo, Shinya

2014-05-01

Observations of Very Metal-Poor stars indicate that there are at least two sites to r-process; "weak r-process" and "main r-process". A question is whether these two are well separated or there exists a variation in the r-process. We present the results of abundance analysis of neutron-capture elements in the two Very Metal-Poor stars HD107752 and HD110184 in the Milky Way halo observed with the Subaru Telescope HDS. The abundance patterns show overabundace at light n-capture elements (e.g. Sr, Y), inferring the element yielding of weak r-process, while heavy neutron-capture elements (e.g. Ba, Eu) are deficient; however, the overabundance of light ones is not as significant as that previously found in stars representing the weak r-process (e.g. HD122563; Honda et al. 2006). Our study show diversity in the abundance patterns from light to heavy neutron-capture elements in VMP stars, suggesting a variation in r-process, which may depend on electron fraction of environment.

Effect of Boron Neutron Capture Therapy (BNCT) on Normal Liver Regeneration: Towards a Novel Therapy for Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jorge E. Cardoso; Elisa M. Heber; David W. Nigg

2007-10-01

The “TAORMINA project” developed a new method for Boron Neutron Capture Therapy (BNCT) of human multifocal unresectable liver metastases based on whole liver ex-situ BNCT mediated by boronophenylalanine (BPA), followed by whole liver autograft. This technique involved a high risk, prolonged anhepatic phase. The Roffo Institute liver surgeons (JEC) herein propose a novel technique to pursue ex-situ liver BNCT studies with a drastically lower surgical risk for the patient. The technique would involve, sequentially, ex-situ BNCT of left liver segments II and III, partial liver autograft, and induction of partial atrophy of the untreated right liver. The working hypothesis ismore » that the atrophy of the right, untreated, diseased liver would stimulate regeneration of the left, treated, “cured” liver to yield a healthy liver mass, allowing for the resection of the remaining portion of diseased liver. This technique does not involve an anhepatic phase and would thus pose a drastically lower surgical risk to the patient but requires sine qua non that BNCT should not impair the regenerative capacity of normal hepatocytes. The aim of the present study was to assess the effect of therapeutic doses of BNCT mediated by BPA, GB-10 (Na2 10B10H10) or (GB- 10 + BPA) on normal liver regeneration in the Wistar rat employing partial hepatectomy as a regenerative stimulus. BNCT did not cause alterations in the outcome of normal liver regeneration, regenerated liver function or histology. We provide proof of principle to support the development of a novel, promising BNCT technique for the treatment of liver metastases.« less

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

PubMed

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

2000-01-01

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

Stellar neutron capture cross sections of 41K and 45Sc

NASA Astrophysics Data System (ADS)

Heil, M.; Plag, R.; Uberseder, E.; Bisterzo, S.; Käppeler, F.; Mengoni, A.; Pignatari, M.

2016-05-01

The neutron capture cross sections of light nuclei (A <56 ) are important for s -process scenarios since they act as neutron poisons. We report on measurements of the neutron capture cross sections of 41K and 45Sc, which were performed at the Karlsruhe 3.7 MV Van de Graaff accelerator via the activation method in a quasistellar neutron spectrum corresponding to a thermal energy of k T =25 keV. Systematic effects were controlled by repeated irradiations, resulting in overall uncertainties of less than 3%. The measured spectrum-averaged data have been used to normalize the energy-dependent (n ,γ ) cross sections from the main data libraries JEFF-3.2, JENDL-4.0, and ENDF/B-VII.1, and a set of Maxwellian averaged cross sections was calculated for improving the s -process nucleosynthesis yields in AGB stars and in massive stars. At k T =30 keV, the new Maxwellian averaged cross sections of 41K and 45Sc are 19.2 ±0.6 mb and 61.3 ±1.8 mb, respectively. Both values are 20% lower than previously recommended. The effect of neutron poisons is discussed for nuclei with A <56 in general and for the investigated isotopes in particular.

Zn-71 levels populated in neutron-capture-gamma reactions

NASA Astrophysics Data System (ADS)

Huchison, Andrew; Harker, Jessica; Walters, William B.; Waite, Mark; Paul, Rick

2015-04-01

The level structure of 71 Zn was studied via the capture-gamma reaction on a highly-enriched 70 Zn target at the NIST Center for Neutron Research NG-7 beam line. The neutron separation energy was determined to be 5832.5(5) keV. Low-spin levels populated in this reaction will be presented, compared with data from other measurements, and discussed. This material is based on work supported by the US Department of Energy (DOE), Office of Science, Office of Nuclear Physics, under Grant No. DE-FG02-94ER40834.

Neutron capture studies with a short flight path

NASA Astrophysics Data System (ADS)

Walter, Stephan; Heil, Michael; Käppeler, Franz; Plag, Ralf; Reifarth, René

The time of flight (TOF) method is an important tool for the experimental determination of neu- tron capture cross sections which are needed for s-process nucleosynthesis in general, and for analyses of branchings in the s-process reaction path in particular. So far, sample masses of at least several milligrams are required to compensate limitations in the currently available neutron fluxes. This constraint leads to unacceptable backgrounds for most of the relevant unstable branch point nuclei, due to the decay activity of the sample. A possible solution has been proposed by the NCAP project at the University of Frankfurt. A first step in this direction is reported here, which aims at enhancing the sensitivity of the Karlsruhe TOF array by reducing the neutron flight path to only a few centimeters. Though sample masses in the microgram regime can be used by this approach, the increase in neutron flux has to be paid by a higher background from the prompt flash related to neutron production. Test measurements with Au samples are reported.

Gd@C82 metallofullerenes for neutron capture therapy—fullerene solubilization by poly(ethylene glycol)-block-poly(2-(N, N-diethylamino)ethyl methacrylate) and resultant efficacy in vitro

PubMed Central

Horiguchi, Yukichi; Kudo, Shinpei; Nagasaki, Yukio

2011-01-01

Poly(ethylene glycol)-block-poly(2-(N,N-diethylamino)ethyl methacrylate) (PEG-b-PAMA) was found to solubilize fullerenes such as C60, and this technique was applied to metallofullerenes. Gd@C82 was easily dissolved in water in the presence of PEG-b-PAMA without any covalent derivatization, forming a transparent complex about 20–30 nm in diameter. Low cytotoxicity was confirmed in vitro. Neutron irradiation of cultured cells (colon-26 adenocarcinoma) with Gd@C82-PEG-b-PAMA-complexed nanoparticles showed effective cytotoxicity, indicating the effective emission of gamma rays and internal conversion electrons produced from the neutron capture reaction of Gd. This result suggests a potentially valuable approach to gadolinium-based neutron capture therapy. PMID:27877415

Tumor-specific delivery of BSH-3R for boron neutron capture therapy and positron emission tomography imaging in a mouse brain tumor model.

PubMed

Iguchi, Yoshiya; Michiue, Hiroyuki; Kitamatsu, Mizuki; Hayashi, Yuri; Takenaka, Fumiaki; Nishiki, Tei-Ichi; Matsui, Hideki

2015-07-01

Glioblastoma, a malignant brain tumor with poor disease outcomes, is managed in modern medicine by multimodality therapy. Boron neutron capture therapy (BNCT) is an encouraging treatment under clinical investigation. In malignant cells, BNCT consists of two major factors: neutron radiation and boron uptake. To increase boron uptake in cells, we created a mercapto-closo-undecahydrododecaborate ([B12HnSH](2-)2Na(+), BSH) fused with a short arginine peptide (1R, 2R, 3R) and checked cellular uptake in vitro and in vivo. In a mouse brain tumor model, only BSH with at least three arginine domains could penetrate cell membranes of glioma cells in vitro and in vivo. Furthermore, to monitor the pharmacokinetic properties of these agents in vivo, we fused BSH and BSH-3R with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); DOTA is a metal chelating agent for labeling positron emission tomography (PET) probe with (64)Cu. We administered BSH-DOTA-(64)Cu and BSH-3R-DOTA-(64)Cu to the tumor model through a mouse tail vein and determined the drugs' pharmacokinetics by PET imaging. BSH-3R showed a high uptake in the tumor area on PET imaging. We concluded that BSH-3R is the ideal boron compound for clinical use during BNCT and that in developing this compound for clinical use, the BSH-3R PET probe is essential for pharmacokinetic imaging. Copyright © 2015 Elsevier Ltd. All rights reserved.

DNA Double-strand Breaks Induced byFractionated Neutron Beam Irradiation for Boron Neutron Capture Therapy.

PubMed

Kinashi, Yuko; Yokomizo, Natsuya; Takahashi, Sentaro

2017-04-01

To use the 53BP1 foci assay to detect DNA double-strand breaks induced by fractionated neutron beam irradiation of normal cells. The Kyoto University Research Reactor heavy-water facility and gamma-ray irradiation system were used as experimental radiation sources. After fixation of Chinese Hamster Ovary cells with 3.6% formalin, immunofluorescence staining was performed. Number and size of foci were analyzed using ImageJ software. Fractionated neutron irradiation induced 25% fewer 53BP1 foci than single irradiation at the same dose. By contrast, gamma irradiation induced 30% fewer 53BP1 foci than single irradiation at the same dose. Fractionated neutron irradiation induced larger foci than gamma irradiation, raising the possibility that persistent unrepaired DNA damage was amplified due to the high linear energy transfer component in the neutron beam. Unrepaired cluster DNA damage was more prevalent after fractionated neutron irradiation than after gamma irradiation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents.

PubMed

Kaniowski, Damian; Ebenryter-Olbińska, Katarzyna; Sobczak, Milena; Wojtczak, Błażej; Janczak, Sławomir; Leśnikowski, Zbigniew J; Nawrot, Barbara

2017-08-23

Boron cluster-modified therapeutic nucleic acids with improved properties are of interest in gene therapy and in cancer boron neutron capture therapy (BNCT). High metallacarborane-loaded antisense oligonucleotides (ASOs) targeting epidermal growth factor receptor (EGFR) were synthesized through post-synthetic Cu (I)-assisted "click" conjugation of alkyne-modified DNA-oligonucleotides with a boron cluster alkyl azide component. The obtained oligomers exhibited increased lipophilicity compared to their non-modified precursors, while their binding affinity to complementary DNA and RNA strands was slightly decreased. Multiple metallacarborane residues present in the oligonucleotide chain, each containing 18 B-H groups, enabled the use of IR spectroscopy as a convenient analytical method for these oligomers based on the diagnostic B-H signal at 2400-2650 cm -1 . The silencing activity of boron cluster-modified ASOs used at higher concentrations was similar to that of unmodified oligonucleotides. The screened ASOs, when used in low concentrations (up to 50 μM), exhibited pro-oxidative properties by inducing ROS production and an increase in mitochondrial activities in HeLa cells. In contrast, when used at higher concentrations, the ASOs exhibited anti-oxidative properties by lowering ROS species levels. In the HeLa cells (tested in the MTT assay) treated (without lipofectamine) or transfected with the screened compounds, the mitochondrial activity remained equal to the control level or only slightly changed (±30%). These findings may be useful in the design of dual-action boron cluster-modified therapeutic nucleic acids with combined antisense and anti-oxidant properties.

Neutron-capture Cl-36, Ca-41, Ar-36, and Sm-150 in large chondrites: Evidence for high fluences of thermalized neutrons

NASA Technical Reports Server (NTRS)

Bogard, D. D.; Nyquist, L. E.; Bansal, B. M.; Garrison, D. H.; Wiesmann, H.; Herzog, G. F.; Albrecht, A. A.; Vogt, S.; Klein, J.

1995-01-01

We have measured significant concentrations of Cl-36, Ca-41, Ar-36 from decay of Cl-36, and Sm-150 produced from the capture of thermalized neutrons in the large Chico L6 chondrite. Activities of Cl-36 and Ca-41, corrected for a high-energy spallogenic component and a terrestrial age of approximately 50 ka, give average neutron-capture production rates of 208 atoms/min/g-Cl and 1525 atoms/min/kg-Ca, which correspond to thermal neutron (n) fluxes of 6.2 n/sq cm/s and 4.3 n/sq cm/s, respectively. If sustained for the approximately 65 Ma single-stage, cosmic ray exposure age of Chico, these values correspond to thermal neutron fluences of approximately 1.3 x 10(exp 16) and 0.8 x 10(exp 16) n/sq cm for Cl-36 and Ca-41, respectively. Stepwise temperature extraction of Ar in Chico impact melt shows Ar-36/Ar-38 ratios as large as approximately 9. The correlation of high Ar-36/Ar-38 with high Cl/Ca phases in neutron-irradiated Chico indicates that the excess Ar-36 above that expected from spallation is due to decay of neutron-produced Cl-36. Excess Ar-36 in Chico requires a thermal neutron fluence of 0.9-1.7 x 10(exp 16) n/sq cm. Decreases in Sm-149/Sm-152 due to neutron-capture by Sm-149 correlate with increases in Sm-150/Sm-152 for three samples of Chico, and one of the Torino H-chondrite. The 0.08% decrease in Sm-149 shown by Chico corresponds to a neutron fluence of 1.23 x 10(exp 16) n/sq cm. This fluence derived from Sm considers capture of epithermal neutrons and effects of chemical composition on the neutron energy distribution. Excess Ar-36 identified in the Arapahoe, Bruderheim, and Torino chondrites and the Shallowater aubrite suggest exposure to neutron fluences of approximately 0.2-0.2 x 10(exp 16) n/sq cm. Depletion of Sm-149 in Torino and the LEW86010 angrite suggest neutron fluences of 0.8 x 10(exp 16) n/sq cm and 0.25 x 10(exp 16) n/sq cm, respectively. Neutron fluences of approximately 10(exp 16) n/sq cm in Chico are almost as large as those previously

Measurement of gamma-ray production from thermal neutron capture on gadolinium for neutrino experiments

NASA Astrophysics Data System (ADS)

Yano, Takatomi; 2012B0025 Collaboration; 2014B0126 Collaboration

2017-02-01

Recently, several scientific applications of gadolinium are found in neutrino physics experiments. Gadolinium-157 is the nucleus, which has the largest thermal neutron capture cross-section among all stable nuclei. Gadolinium-155 also has the large cross-section. These neutron capture reactions provide the gamma-ray cascade with the total energy of about 8 MeV. This reaction is applied for several neutrino experiments, e.g. reactor neutrino experiments and Gd doped large water Cherenkov detector experiments, to recognize inverse-beta-decay reaction. A good Gd(n,γ) simulation model is needed to evaluate the detection efficiency of the neutron capture reaction, i.e. the efficiency of IBD detection. In this presentation, we will report the development and study status of a Gd(n,γ) calculation model and comparison with our experimental data taken at ANNRI/MLF beam line, J-PARC.

Microdosimetric Modeling of Biological Effectiveness for Boron Neutron Capture Therapy Considering Intra- and Intercellular Heterogeneity in 10B Distribution.

PubMed

Sato, Tatsuhiko; Masunaga, Shin-Ichiro; Kumada, Hiroaki; Hamada, Nobuyuki

2018-01-17

We here propose a new model for estimating the biological effectiveness for boron neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity in 10 B distribution. The new model was developed from our previously established stochastic microdosimetric kinetic model that determines the surviving fraction of cells irradiated with any radiations. In the model, the probability density of the absorbed doses in microscopic scales is the fundamental physical index for characterizing the radiation fields. A new computational method was established to determine the probability density for application to BNCT using the Particle and Heavy Ion Transport code System PHITS. The parameters used in the model were determined from the measured surviving fraction of tumor cells administrated with two kinds of 10 B compounds. The model quantitatively highlighted the indispensable need to consider the synergetic effect and the dose dependence of the biological effectiveness in the estimate of the therapeutic effect of BNCT. The model can predict the biological effectiveness of newly developed 10 B compounds based on their intra- and intercellular distributions, and thus, it can play important roles not only in treatment planning but also in drug discovery research for future BNCT.

Excitations of one-valence-proton, one-valence-neutron nucleus {sup 210}Bi from cold-neutron capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cieplicka-Oryńczak, N.; Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Kraków; Fornal, B.

2015-10-15

The low-spin structure of one-proton, one-neutron {sup 210}Bi nucleus was investigated in cold-neutron capture reaction on {sup 209}Bi. The γ-coincidence measurements were performed with use of EXILL array consisted of 16 HPGe detectors. The experimental results were compared to shell-model calculations involving valence particles excitations. The {sup 210}Bi nucleus offers the potential to test the effective proton-neutron interactions because most of the states should arise from the proton-neutron excitations. Additionally, it was discovered that a few states should come from the couplings of valence particles to the 3{sup −} octupole vibration in {sup 208}Pb which provides also the possibility ofmore » testing the calculations involving the core excitations.« less

Rates for neutron-capture reactions on tungsten isotopes in iron meteorites. [Abstract only

NASA Technical Reports Server (NTRS)

Masarik, J.; Reedy, R. C.

1994-01-01

High-precision W isotopic analyses by Harper and Jacobsen indicate the W-182/W-183 ratio in the Toluca iron meteorite is shifted by -(3.0 +/- 0.9) x 10(exp -4) relative to a terrestrial standard. Possible causes of this shift are neutron-capture reactions on W during Toluca's approximately 600-Ma exposure to cosmic ray particles or radiogenic growth of W-182 from 9-Ma Hf-182 in the silicate portion of the Earth after removal of W to the Earth's core. Calculations for the rates of neutron-capture reactions on W isotopes were done to study the first possibility. The LAHET Code System (LCS) which consists of the Los Alamos High Energy Transport (LAHET) code and the Monte Carlo N-Particle(MCNP) transport code was used to numerically simulate the irradiation of the Toluca iron meteorite by galactic-cosmic-ray (GCR) particles and to calculate the rates of W(n, gamma) reactions. Toluca was modeled as a 3.9-m-radius sphere with the composition of a typical IA iron meteorite. The incident GCR protons and their interactions were modeled with LAHET, which also handled the interactions of neutrons with energies above 20 MeV. The rates for the capture of neutrons by W-182, W-183, and W-186 were calculated using the detailed library of (n, gamma) cross sections in MCNP. For this study of the possible effect of W(n, gamma) reactions on W isotope systematics, we consider the peak rates. The calculated maximum change in the normalized W-182/W-183 ratio due to neutron-capture reactions cannot account for more than 25% of the mass 182 deficit observed in Toluca W.

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

PubMed

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

2016-10-01

A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2015-01-01

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

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

PubMed

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

2017-09-30

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

Neutron capture cross section of {sup 14}C of astrophysical interest studied by Coulomb breakup of {sup 15}C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, T.; Fukuda, N.; Aoi, N.

2009-03-15

The neutron capture reaction on {sup 14}C leading to the {sup 15}C ground state, which plays an important role in various nucleosynthesis processes, has been studied using the Coulomb breakup of {sup 15}C on a Pb target at 68 MeV/nucleon. The breakup cross section has been converted into the energy-dependent neutron capture cross section using the principle of detailed balance. The energy spectrum shows typical p-wave neutron capture characteristics, which is explained by the fact that the ground state of {sup 15}C possesses a strong single-particle s-wave component and a moderate-sized neutron halo structure. The capture cross section for themore » {sup 14}C(n,{gamma}){sup 15}C reaction derived from the present experiment has been found to be consistent with the most recent data, directly measured using a {sup 14}C target. This result assures the validity of the Coulomb breakup method in deriving the neutron capture cross section for neutron-rich nuclei.« less

Neutron therapy for salivary and thyroid gland cancer

NASA Astrophysics Data System (ADS)

Gribova, O. V.; Musabaeva, L. I.; Choynzonov, E. L.; Lisin, V. A.; Novikov, V. A.

2016-08-01

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

Neutron therapy for salivary and thyroid gland cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gribova, O. V., E-mail: gribova79@mail.ru; Choynzonov, E. L., E-mail: nii@oncology.tomsk.ru; National Research Tomsk Polytechnic University, Lenina Avenue 30, Tomsk, 634050

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

An overview of DANCE: a 4II BaF[2] detector for neutron capture measurements at LANSCE.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ullmann, J. L.

2004-01-01

The Detector for Advanced Neutron Capture experiments (DANCE) is a 162-element, 4{pi} BaF{sub 2} array designed to make neutron capture cross-section measurements on rare or radioactive targets with masses as little as 1 mg. Accurate capture cross sections are needed in many research areas, including stellar nucleosynthesis, advanced nuclear fuel cycles, waste transmutation, and other applied programs. These cross sections are difficult to calculate accurately and must be measured. Up to now, except for a few long-lived nuclides there are essentially no differential capture measurements on radioactive nuclei. The DANCE array is located at the Lujan Neutron Scattering Center atmore » LANSCE, which is a continuous-spectrum neutron source with useable energies from below thermal to about 100 keV. Data acquisition is done with 320 fast waveform digitizers. The design and initial performance results, including background minimization, will be discussed.« less

Isomeric ratio measurements for the radiative neutron capture 176Lu(n,γ) at DANCE

NASA Astrophysics Data System (ADS)

Denis-Petit, D.; Roig, O.; Méot, V.; Morillon, B.; Romain, P.; Jandel, M.; Kawano, T.; Vieira, D. J.; Bond, E. M.; Bredeweg, T. A.; Couture, A. J.; Haight, R. C.; Keksis, A. L.; Rundberg, R. S.; Ullmann, J. L.

2017-09-01

The isomeric ratios for the neutron capture reaction 176Lu(n,γ) to the Jπ = 5/2-, 761.7 keV, T1/2 = 32.8 ns and the Jπ = 15/2+, 1356.9 keV, T1/2 = 11.1 ns levels of 177Lu, have been measured for the first time with the Detector for Advanced Neutron Capture Experiments (DANCE) at the Los Alamos National Laboratory. These measured isomeric ratios are compared with TALYS calculations.

Near-Ultraviolet Observations of CS 29497-030: New Constraints on Neutron-Capture Nucleosynthesis Processes

NASA Astrophysics Data System (ADS)

Ivans, Inese I.; Sneden, Christopher; Gallino, Roberto; Cowan, John J.; Preston, George W.

2005-07-01

Employing spectra obtained with the new Keck I HIRES near-UV-sensitive detector, we have performed a comprehensive chemical composition analysis of the binary blue metal-poor star CS 29497-030. Abundances for 29 elements and upper limits for an additional seven have been derived, concentrating on elements largely produced by means of neutron-capture nucleosynthesis. Included in our analysis are the two elements that define the termination point of the slow neutron-capture process, lead and bismuth. We determine an extremely high value of [Pb/Fe]=+3.65+/-0.07 (σ=0.13) from three features, supporting the single-feature result obtained in previous studies. We detect Bi for the first time in a metal-poor star. Our derived Bi/Pb ratio is in accord with those predicted from the most recent FRANEC calculations of the slow neutron-capture process in low-mass asymptotic giant branch (AGB) stars. We find that the neutron-capture elemental abundances of CS 29497-030 are best explained by an AGB model that also includes very significant amounts of pre-enrichment of rapid neutron-capture process material in the protostellar cloud out of which the CS 29497-030 binary system formed. Mass transfer is consistent with the observed [Nb/Zr]~0. Thus, CS 29497-030 is both an r+s and ``extrinsic AGB'' star. Furthermore, we find that the mass of the AGB model can be further constrained by the abundance of the light odd-element Na. The data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

First neutron generation in the BINP accelerator based neutron source.

PubMed

Bayanov, B; Burdakov, A; Chudaev, V; Ivanov, A; Konstantinov, S; Kuznetsov, A; Makarov, A; Malyshkin, G; Mekler, K; Sorokin, I; Sulyaev, Yu; Taskaev, S

2009-07-01

Pilot innovative facility for neutron capture therapy was built at Budker Institute of Nuclear Physics, Novosibirsk. This facility is based on a compact vacuum insulation tandem accelerator designed to produce proton current up to 10 mA. Epithermal neutrons are proposed to be generated by 1.915 MeV protons bombarding a lithium target using (7)Li(p,n)(7)Be threshold reaction. The results of the first experiments on neutron generation are reported and discussed.

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

PubMed

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

2014-03-01

The 9Be(d,n)10B reaction was studied as an epithermal neutron source for brain tumor treatment through Boron Neutron Capture Therapy (BNCT). In BNCT, neutrons are classified according to their energies as thermal (<0.5 eV), epithermal (from 0.5 eV to 10 keV) or fast (>10 keV). For deep-seated tumors epithermal neutrons are needed. Since a fraction of the neutrons produced by this reaction are quite fast (up to 5-6 MeV, even for low-bombarding energies), an efficient beam shaping design is required. This task was carried out (1) by selecting the combinations of bombarding energy and target thickness that minimize the highest-energy neutron production; and (2) by the appropriate choice of the Beam Shaping Assembly (BSA) geometry, for each of the combinations found in (1). The BSA geometry was determined as the configuration that maximized the dose deliverable to the tumor in a 1 h treatment, within the constraints imposed by the healthy tissue dose adopted tolerance. Doses were calculated through the MCNP code. The highest dose deliverable to the tumor was found for an 8 μm target and a deuteron beam of 1.45 MeV. Tumor weighted doses ≥40 Gy can be delivered up to about 5 cm in depth, with a maximum value of 51 Gy at a depth of about 2 cm. This dose performance can be improved by relaxing the treatment time constraint and splitting the treatment into two 1-h sessions. These good treatment capabilities strengthen the prospects for a potential use of this reaction in BNCT. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Ullmann, J. L.

2014-09-01

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

Contribution of Massive Stars to the Production of Neutron Capture Elements

NASA Astrophysics Data System (ADS)

Federman, Steven

2010-09-01

Elements beyond the Fe-peak must be synthesized through neutron-capture processes. With the aim of understanding the contribution of massive stars to the synthesis of neutron-capture elements during the current epoch, we propose an archival survey of interstellar arsenic, cadmium, tin, and lead. Nucleosynthesis via the weak slow process and the rapid process are the routes involving massive stars, while the main slow process arises from the evolution of low-mass stars. Ultraviolet lines for the dominant ions for each element will be used to extract interstellar abundances. The survey involves about forty sight lines, many of which are associated with regions of massive star formation shaped by core-collapse supernovae {SNe II}. The sample will increase the number of published determinations by factors of 2 to 5. HST spectra are the only means for determining the elemental abundances for this set of species in diffuse interstellar clouds. The survey contains directions that are both molecule poor and molecule rich, thereby enabling us to examine the overall level of depletion onto grains as a function of gas density. Complementary laboratory determinations of oscillator strengths will place the interstellar measurements on an absolute scale. The results from the proposed study will be combined with published interstellar abundances for other neutron capture elements and the suite of measurements will be compared to results from stars throughout the history of the Galaxy.

Validating (d,p gamma) as a Surrogate for Neutron Capture

DOE PAGES

Ratkiewicz, A.; Cizewski, J.A.; Pain, S.D.; ...

2015-05-28

The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate formore » (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions.« less

Neutron-Capture Elements in Very Metal-Poor Halo Stars

NASA Astrophysics Data System (ADS)

French, R. S.; Sneden, C.; Cowan, J. J.; Lawler, J. E.; Primas, F.; Beers, T. C.; Truran, J. W.

2000-05-01

Abundances of the most massive stable elements (Os -> Pb or 76 <= Z <= 82) in metal-poor stars can provide crucial information about the so-called ``third neutron-capture peak,'' and are critical to the radioactive-dating technique that uses unstable thorium and uranium as chronometers. As the relevant transitions occur in the UV and are inaccessable to ground-based telescopes, we have obtained high resolution (R ~= 30,000) UV spectra of 10 very metal-poor (--3.0 <= [Fe/H] <= --1.4) halo giants using the Space Telescope Imaging Spectrograph (STIS) aboard the Hubble Space Telescope. Using iterative spectrum synthesis techniques, we derive abundances for some of these heavy elements. We compare our abundances to those predicted for very metal-poor stars based on a scaled solar system rapid-process (production in rapid neutron-capture synthesis events, such as occurs during supernovae explosions). This research is supported by NASA STScI grant GO-08342 and NSF grants AST-9618364 to C.S. and AST-9618332 to J.J.C.

Neutron therapy of resistant thyroid gland cancer

NASA Astrophysics Data System (ADS)

Choynzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Lisin, V. A.; Novikov, V. A.; Musabaeva, L. I.

2017-09-01

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons c. The study included 45 patients with thyroid gland cancers who received the combined modality treatment and radiation therapy alone with the use of 6.3 MeV fast neutrons generated within U-120 cyclotron. The clinical trial of neutron-photon therapy used alone and in combination with the surgery for the patients with aggressive forms of thyroid cancer showed feasibility of increasing the effectiveness of treatment due to the reduction in the incidence of local recurrences. In addition, satisfactory treatment tolerance and absence of severe specific complications dictate the necessity of prospective studies to improve treatment outcomes.

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

PubMed

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

2006-02-01

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

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

PubMed

Brandão, S F; Campos, T P R

2015-07-01

This article proposes a combination of californium-252 ((252)Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Dosimetric evaluations were performed on three protocol set-ups: (252)Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0-5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the (252)Cf source, sparing the normal brain tissue. Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis.

In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capture therapy of cancer.

PubMed

Shikata, Futoshi; Tokumitsu, Hiroyuki; Ichikawa, Hideki; Fukumori, Yoshinobu

2002-01-01

The accumulation of gadolinium loaded as gadopentetic acid (Gd-DTPA) in chitosan nanoparticles (Gd-nanoCPs), which were designed for gadolinium neutron-capture therapy (Gd-NCT) for cancer, was evaluated in vitro in cultured cells. Using L929 fibroblast cells, the Gd accumulation for 12 h at 37 degrees C was investigated at Gd concentrations lower than 40 ppm. The accumulation leveled above 20 ppm and reached 18.0+/-2.7 (mean+/-S.D.) microg Gd/10(6) cells at 40 ppm. Furthermore, the corresponding accumulations in B16F10 melanoma cells and SCC-VII squamous cell carcinoma, which were used in the previous Gd-NCT trials in vivo, were 27.1+/-2.9 and 59.8+/-9.8 microg Gd/10(6) cells, respectively, hence explaining the superior growth-suppression in the in vivo trials using SCC-VII cells. The accumulation of Gd-nanoCPs in these cells was 100-200 times higher in comparison to dimeglumine gadopentetate aqueous solution (Magnevist), a magnetic resonance imaging contrast agent. The endocytic uptake of Gd-nanoCPs, strongly holding Gd-DTPA, was suggested from transmission electron microscopy and comparative studies at 4 degrees C and with the solution system. These findings indicated that Gd-nanoCPs had a high affinity to the cells, probably contributing to the long retention of Gd in tumor tissue and leading to the significant suppression of tumor growth in the in vivo studies that were previously reported.

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

PubMed

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

2015-07-15

A library of sixteen 2nd generation amino- and amido-substituted carboranyl pyrimidine nucleoside analogs, designed as substrates and inhibitors of thymidine kinase 1 (TK1) for potential use in boron neutron capture therapy (BNCT) of cancer, was synthesized and evaluated in enzyme kinetic-, enzyme inhibition-, metabolomic-, and biodistribution studies. One of these 2nd generation carboranyl pyrimidine nucleoside analogs (YB18A [3]), having an amino group directly attached to a meta-carborane cage tethered via ethylene spacer to the 3-position of thymidine, was approximately 3-4 times superior as a substrate and inhibitor of hTK1 than N5-2OH (2), a 1st generation carboranyl pyrimidine nucleoside analog. Both 2 and 3 appeared to be 5'-monophosphorylated in TK1(+) RG2 cells, both in vitro and in vivo. Biodistribution studies in rats bearing intracerebral RG2 glioma resulted in selective tumor uptake of 3 with an intratumoral concentration that was approximately 4 times higher than that of 2. The obtained results significantly advance the understanding of the binding interactions between TK1 and carboranyl pyrimidine nucleoside analogs and will profoundly impact future design strategies for these agents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Measurement of the Parity-Violating directional Gamma-ray Asymmetry in Polarized Neutron Capture on ^35Cl

NASA Astrophysics Data System (ADS)

Fomin, Nadia

2012-03-01

The NPDGamma experiment aims to measure the parity-odd correlation between the neutron spin and the direction of the emitted photon in neutron-proton capture. A parity violating asymmetry (to be measured to 10-8) from this process can be directly related to the strength of the hadronic weak interaction between nucleons. As part of the commissioning runs on the Fundamental Neutron Physics beamline at the Spallation Neutron Source at ORNL, the gamma-ray asymmetry from the parity-violating capture of cold neutrons on ^35Cl was measured, primarily to check for systematic effects and false asymmtries. The current precision from existing world measurements on this asymmetry is at the level of 10-6 and we believe we can improve it. The analysis methodology as well as preliminary results will be presented.

Avidin self-associates with boric acid gel suspensions: an affinity boron carrier that might be developed for boron neutron-capture therapy.

PubMed

Bench, Bennie J; Johnson, Rebecca; Hamilton, Craig; Gooch, Joey; Wright, John R

2004-02-15

It has been shown in preliminary studies that the antibacterial protein avidin self-associates with the boric acid gel polymer, and avidin-coated gel particles in the micrometer and submicrometer size ranges are of interest for boron neutron-capture therapy (BNCT), which is neutron-induced fission of boron-10 to produce intense alpha radiation for tumor destruction. The gel particles carry large amounts of boron-10 and are theoretically able effect a meaningful tissue dosing through BNCT. A gross precipitation of gel particles occurs within 46 min of mixing when the avidin/colloid ratio is about 0.34 g avidin/g colloid. This is a minimum time if gel and avidin concentrations are in the low microgram/milliliter range, but at higher proportions of avidin the time delay to precipitation increases significantly; i.e., the colloid surface becomes blocked, inhibiting lattice formation. The avidin-coated gel particles eventually cross-link, forming a solid matrix and precipitating on a timescale measured on the order of an hour. At shorter exposure times rapid agglutination-like reactions were observed with biotinylated bovine albumin, suggesting that two-stage pretargeting of specific tissues should be possible with biotinylated antitumor antibodies. However, for BNCT to be practical, avidin's interaction with the gel needs to be strengthened, and all aryl-B(OH)(2) groups on the particle surfaces must be blocked, or else the particles will interact strongly and nonspecifically with each other and with the carbohydrate groups present on most cell surfaces. Glyceric acid delays the precipitation of the particle suspensions while most simple and complex carbohydrates accelerate it.

First application of dynamic infrared imaging in boron neutron capture therapy for cutaneous malignant melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santa Cruz, G. A.; Gonzalez, S. J.; Bertotti, J.

2009-10-15

Purpose: The purpose of this study is to assess the potential of dynamic infrared imaging (DIRI) as a functional, noninvasive technique for evaluating the skin acute toxicity and tumor control within the framework of the Argentine boron neutron capture therapy (BNCT) program for cutaneous malignant melanoma. Methods: Two patients enrolled in the Argentine phase I/II BNCT clinical trial for cutaneous malignant melanoma were studied with DIRI. An uncooled infrared camera, providing a video output signal, was employed to register the temperature evolution of the normal skin and tumor regions in patients subjected to a mild local cooling (cold stimulus). Inmore » order to study the spatial correlation between dose and acute skin reactions, three-dimensional representations of the superficial dose delivered to skin were constructed and cameralike projections of the dose distribution were coregistered with visible and infrared images. Results: The main erythematous reaction was observed clinically between the second and fifth week post-BNCT. Concurrently, with its clinical onset, a reactive increase above the basal skin temperature was observed with DIRI in the third week post-BNCT within regions that received therapeutic doses. Melanoma nodules appeared as highly localized hyperthermic regions. 2 min after stimulus, these regions reached a temperature plateau and increased in size. Temperature differences with respect to normal skin up to 10 deg. C were observed in the larger nodules. Conclusions: Preliminary results suggest that DIRI, enhanced by the application of cold stimuli, may provide useful functional information associated with the metabolism and vasculature of tumors and inflammatory processes related to radiation-induced changes in the skin as well. These capabilities are aimed at complementing the clinical observations and standard imaging techniques, such as CT and Doppler ultrasound.« less

Accelerator based epithermal neutron source

NASA Astrophysics Data System (ADS)

Taskaev, S. Yu.

2015-11-01

We review the current status of the development of accelerator sources of epithermal neutrons for boron neutron capture therapy (BNCT), a promising method of malignant tumor treatment. Particular attention is given to the source of epithermal neutrons on the basis of a new type of charged particle accelerator: tandem accelerator with vacuum insulation and lithium neutron-producing target. It is also shown that the accelerator with specialized targets makes it possible to generate fast and monoenergetic neutrons, resonance and monoenergetic gamma-rays, alpha-particles, and positrons.

Neutron collimator design of neutron radiography based on the BNCT facility

NASA Astrophysics Data System (ADS)

Yang, Xiao-Peng; Yu, Bo-Xiang; Li, Yi-Guo; Peng, Dan; Lu, Jin; Zhang, Gao-Long; Zhao, Hang; Zhang, Ai-Wu; Li, Chun-Yang; Liu, Wan-Jin; Hu, Tao; Lü, Jun-Guang

2014-02-01

For the research of CCD neutron radiography, a neutron collimator was designed based on the exit of thermal neutron of the Boron Neutron Capture Therapy (BNCT) reactor. Based on the Geant4 simulations, the preliminary choice of the size of the collimator was determined. The materials were selected according to the literature data. Then, a collimator was constructed and tested on site. The results of experiment and simulation show that the thermal neutron flux at the end of the neutron collimator is greater than 1.0×106 n/cm2/s, the maximum collimation ratio (L/D) is 58, the Cd-ratio(Mn) is 160 and the diameter of collimator end is 10 cm. This neutron collimator is considered to be applicable for neutron radiography.

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

PubMed Central

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

2013-01-01

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

Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma.

PubMed

Perona, M; Rodríguez, C; Carpano, M; Thomasz, L; Nievas, S; Olivera, M; Thorp, S; Curotto, P; Pozzi, E; Kahl, S; Pisarev, M; Juvenal, G; Dagrosa, A

2013-08-01

We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated thyroid carcinoma (PDTC). Histone deacetylase inhibitors (HDACI) like sodium butyrate (NaB) cause hyperacetylation of histone proteins and show capacity to increase the gamma irradiation effect. The purpose of these studies was to investigate the use of the NaB as a radiosensitizer of the BNCT for PDTC. Follicular thyroid carcinoma cells (WRO) and rat thyroid epithelial cells (FRTL-5) were incubated with 1 mM NaB and then treated with boronophenylalanine ¹⁰BPA (10 μg ¹⁰B ml⁻¹) + neutrons, or with 2, 4-bis (α,β-dihydroxyethyl)-deutero-porphyrin IX ¹⁰BOPP (10 μg ¹⁰B ml⁻¹) + neutrons, or with a neutron beam alone. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux = (1.0 ± 0.1) × 10¹⁰ n cm⁻² s⁻¹). Cell survival decreased as a function of the physical absorbed dose in both cell lines. Moreover, the addition of NaB decreased cell survival (p < 0.05) in WRO cells incubated with both boron compounds. NaB increased the percentage of necrotic and apoptotic cells in both BNCT groups (p < 0.05). An accumulation of cells in G2/M phase at 24 h was observed for all the irradiated groups and the addition of NaB increased this percentage. Biodistribution studies of BPA (350 mg kg⁻¹ body weight) 24 h after NaB injection were performed. The in vivo studies showed that NaB treatment increases the amount of boron in the tumor at 2-h post-BPA injection (p < 0.01). We conclude that NaB could be used as a radiosensitizer for the treatment of thyroid carcinoma by BNCT.

Boron neutron capture therapy (BNCT) for glioblastoma multiforme: a phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA).

PubMed

Henriksson, Roger; Capala, Jacek; Michanek, Annika; Lindahl, Sten-Ake; Salford, Leif G; Franzén, Lars; Blomquist, Erik; Westlin, Jan-Erik; Bergenheim, A Tommy

2008-08-01

To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion. This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. The boron-blood concentration during irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells.

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

PubMed Central

Brandão, S F

2015-01-01

Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

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

PubMed

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

2015-12-01

The iBNCT project team with University of Tsukuba is developing an accelerator-based neutron source. Regarding neutron target material, our project has applied beryllium. To deal with large heat load and blistering of the target system, we developed a three-layer structure for the target system that includes a blistering mitigation material between the beryllium used as the neutron generator and the copper heat sink. The three materials were bonded through diffusion bonding using a hot isostatic pressing method. Based on several verifications, our project chose palladium as the intermediate layer. A prototype of the neutron target system was produced. We will verify that sufficient neutrons for BNCT treatment are generated by the device in the near future. Copyright © 2015 Elsevier Ltd. All rights reserved.

SU-E-J-115: Graticule for Verification of Treatment Position in Neutron Therapy.

PubMed

Halford, R; Snyder, M

2012-06-01

Until recently the treatment verification for patients undergoing fast neutron therapy at our facility was accomplished through a combination of neutron beam portal films aligned with a graticule mounted on an orthronormal x-ray tube. To eliminate uncertainty with respect to the relative positions of the x-ray graticule and the therapy beam, we have developed a graticule which is placed in the neutron beam itself. For a graticule to be visible on the portal film, the attenuation of the neutron beam by the graticule landmarks must be significantly greater than that of the material in which the landmarks are mounted. Various materials, thicknesses, and mounting points were tried to gain the largest contrast between the graticule landmarks and the mounting material. The final design involved 2 inch steel pins of 0.125 inch diameter captured between two parallel plates of 0.25 inch thick clear acrylic plastic. The distance between the two acrylic plates was 1.625 inches, held together at the perimeter with acrylic sidewall spacers. This allowed the majority of length of the steel pins to be surrounded by air. The pins were set 1 cm apart and mounted at angles parallel to the divergence of the beam dependent on their position within the array. The entire steel pin and acrylic plate assembly was mounted on an acrylic accessory tray to allow for graticule alignment. Despite the inherent difficulties in attenuating fast neutrons, our simple graticule design produces the required difference of attenuation between the arrays of landmarks and the mounting material. The graticule successfully provides an in-beam frame of reference for patient portal verification. © 2012 American Association of Physicists in Medicine.

Cadmium Isotope Variations in Bulk Chondrites: The Effect of Thermal Neutron Capture

NASA Astrophysics Data System (ADS)

Toth, E. R.; Schönbächler, M.; Friebel, M.; Fehr, M. A.

2017-07-01

Cadmium isotope data will be presented for bulk carbonaceous and enstatite chondrites, and acid leachates of Jbilet Winselwan (CM). Results of bulk samples show Cd isotope variations that are in good agreement with models of thermal neutron capture.

Evaluation of neutron capture cross section on 205Pb with photonuclear data

NASA Astrophysics Data System (ADS)

Iwamoto, Nobuyuki; Shizuma, Toshiyuki

2018-05-01

The neutron capture cross section of long-lived radioactive 205Pb is derived by using the nuclear reaction calculation code CCONE, based on photonuclear data. The present result is smaller than that of TENDL-2015 by a factor of 4. The derived Maxwellian averaged capture cross section (MACS) is the smallest compared to the existing data. The produced amount of 205Pb is explored with a simulated neutron flux in the Pb-Bi eutectic (LBE) target. The continuous use of the system in 25 years creates 205Pb with about 6 kg at maximum in the LBE (including natural Pb of 103 kg). The impact of the derived MACS on the stellar nucleosynthesis is investigated. It is found that the abundance of Tl is slightly enhanced due to the increase in the remaining abundance of 205Pb.

Neutron capture cross section measurement of 151Sm at the CERN neutron time of flight facility (n_TOF).

PubMed

Abbondanno, U; Aerts, G; Alvarez-Velarde, F; Alvarez-Pol, H; Andriamonje, S; Andrzejewski, J; Badurek, G; Baumann, P; Becvár, F; Benlliure, J; Berthoumieux, E; Calviño, F; Cano-Ott, D; Capote, R; Cennini, P; Chepel, V; Chiaveri, E; Colonna, N; Cortes, G; Cortina, D; Couture, A; Cox, J; Dababneh, S; Dahlfors, M; David, S; Dolfini, R; Domingo-Pardo, C; Duran, I; Embid-Segura, M; Ferrant, L; Ferrari, A; Ferreira-Marques, R; Frais-Koelbl, H; Furman, W; Goncalves, I; Gallino, R; Gonzalez-Romero, E; Goverdovski, A; Gramegna, F; Griesmayer, E; Gunsing, F; Haas, B; Haight, R; Heil, M; Herrera-Martinez, A; Isaev, S; Jericha, E; Käppeler, F; Kadi, Y; Karadimos, D; Kerveno, M; Ketlerov, V; Koehler, P; Konovalov, V; Krticka, M; Lamboudis, C; Leeb, H; Lindote, A; Lopes, I; Lozano, M; Lukic, S; Marganiec, J; Marrone, S; Martinez-Val, J; Mastinu, P; Mengoni, A; Milazzo, P M; Molina-Coballes, A; Moreau, C; Mosconi, M; Neves, F; Oberhummer, H; O'Brien, S; Pancin, J; Papaevangelou, T; Paradela, C; Pavlik, A; Pavlopoulos, P; Perlado, J M; Perrot, L; Pignatari, M; Plag, R; Plompen, A; Plukis, A; Poch, A; Policarpo, A; Pretel, C; Quesada, J; Raman, S; Rapp, W; Rauscher, T; Reifarth, R; Rosetti, M; Rubbia, C; Rudolf, G; Rullhusen, P; Salgado, J; Soares, J C; Stephan, C; Tagliente, G; Tain, J; Tassan-Got, L; Tavora, L; Terlizzi, R; Vannini, G; Vaz, P; Ventura, A; Villamarin, D; Vincente, M C; Vlachoudis, V; Voss, F; Wendler, H; Wiescher, M; Wisshak, K

2004-10-15

The151Sm(n,gamma)152Sm cross section has been measured at the spallation neutron facility n_TOF at CERN in the energy range from 1 eV to 1 MeV. The new facility combines excellent resolution in neutron time-of-flight, low repetition rates, and an unsurpassed instantaneous luminosity, resulting in rather favorable signal/background ratios. The 151Sm cross section is of importance for characterizing neutron capture nucleosynthesis in asymptotic giant branch stars. At a thermal energy of kT=30 keV the Maxwellian averaged cross section of this unstable isotope (t(1/2)=93 yr) was determined to be 3100+/-160 mb, significantly larger than theoretical predictions.

New insights on Ba overabundance in open clusters. Evidence for the intermediate neutron-capture process at play?

NASA Astrophysics Data System (ADS)

Mishenina, T.; Pignatari, M.; Carraro, G.; Kovtyukh, V.; Monaco, L.; Korotin, S.; Shereta, E.; Yegorova, I.; Herwig, F.

2015-02-01

Recently, an increasing number of studies were devoted to measure the abundances of neutron-capture elements heavier than iron in stars belonging to Galactic Open Clusters (OCs). OCs span a sizeable range in metallicity (-0.6 ≤ [Fe/H] ≤ +0.4), and they show abundances of light elements similar to disc stars of the same age. A different pattern is observed for heavy elements. A large scatter is observed for Ba, with most OCs showing [Ba/Fe] and [Ba/La] overabundant with respect to the Sun. The origin of this overabundance is not clearly understood. With the goal of providing new observational insights, we determined radial velocities, atmospheric parameters and chemical composition of 27 giant stars members of five OCs: Cr 110, Cr 261, NGC 2477, NGC 2506 and NGC 5822. We used high-resolution spectra obtained with the UVES spectrograph at European Southern Observatory Paranal. We perform a detailed spectroscopic analysis of these stars to measure the abundance of up to 22 elements per star. We study the dependence of element abundance on metallicity and age with unprecedented detail, complementing our analysis with data culled from the literature. We confirm the trend of Ba overabundance in OCs, and show its large dispersion for clusters younger than ˜4 Gyr. Finally, the implications of our results for stellar nucleosynthesis are discussed. We show in this work that the Ba enrichment compared to other neutron-capture elements in OCs cannot be explained by the contributions from the slow neutron-capture process and the rapid neutron-capture process. Instead, we argue that this anomalous signature can be explained by assuming an additional contribution by the intermediate neutron-capture process.

Exposure ages and neutron capture record in lunar samples from Fra Mauro.

NASA Technical Reports Server (NTRS)

Lugmair, G. W.; Marti, K.

1972-01-01

Cosmic-ray exposure ages of Apollo 14 rocks and rock fragments obtained by the Kr81-Kr83 method range from 27 to 700 m.y. Rock 14321, collected near the Cone crater rim, is one of the many approximately 27 m.y. old ejecta which were reported at the Third Lunar Science Conference. All the other rocks have considerably higher exposure ages. Isotopic anomalies from neutron capture in gadolinium, bromine, and barium are used to obtain information on the lunar neutron spectrum at various depths below the lunar surface. The flux ratio of resonance and slow (less than 0.3 eV) neutrons is found to be nearly constant in the topmost approximately 100 g/sq cm.

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

PubMed

Heber, Elisa M; Kueffer, Peter J; Lee, Mark W; Hawthorne, M Frederick; Garabalino, Marcela A; Molinari, Ana J; Nigg, David W; Bauer, William; Hughes, Andrea Monti; Pozzi, Emiliano C C; Trivillin, Verónica A; Schwint, Amanda E

2012-05-01

Boron neutron capture therapy (BNCT) combines selective accumulation of (10)B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na(3) [ae-B(20)H(17)NH(3)], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

David W. Nigg

2012-05-01

Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1)more » MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.« less

Isomeric ratio measurements for the radiative neutron capture 176Lu(n,γ) at DANCE

NASA Astrophysics Data System (ADS)

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

2016-03-01

The isomeric ratio for the neutron capture reaction 176Lu(n,γ) on the Jπ= 5/2-, 761.7 keV, T1/2=32.8 ns level of 177mLu, has been determined in the neutron energy range 8.5 eV-100 keV for the first time using the DANCE array at the Los Alamos National Laboratory.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hawthorne, M. Frederick

2005-04-07

Medical application of boron neutron capture therapy (BNCT) has been significantly hindered by the slow development of boron drug-targeting methodologies for the selective delivery of high boron concentration sto malignant cells. We have successfully sought to fill this need by creating liposomes suitable as in vivo boron delivery vehicles for BNCT. Delivery of therapeutic quantities of boron to tumors in murine models has been achieved with small unilamellar boron-rich liposomes. Subsequently, attempts have been made to improve delivery efficiency of liposomes encapsulating boron-containing water-soluble species into their hollow core by incorporating lipophilic boron compounds as addenda to the liposome bilayer,more » 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

Thymidine kinase 1 as a molecular target for boron neutron capture therapy of brain tumors

PubMed Central

Barth, Rolf F.; Yang, Weilian; Wu, Gong; Swindall, Michele; Byun, Youngjoo; Narayanasamy, Sureshbabu; Tjarks, Werner; Tordoff, Kevin; Moeschberger, Melvin L.; Eriksson, Staffan; Binns, Peter J.; Riley, Kent J.

2008-01-01

The purpose of the present study was to evaluate the effectiveness of a 3-carboranyl thymidine analogue (3CTA), 3-[5-{2-(2,3-dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl] thymidine, designated N5–2OH, for boron neutron capture therapy (BNCT) of brain tumors using the RG2 rat glioma model. Target validation was established using the thymidine kinase (TK) 1(+) wild-type, murine L929 cell line and its TK1(−) mutant counterpart, which were implanted s.c. (s.c.) into nude mice. Two intratumoral (i.t.) injections of 10B-enriched N5–2OH were administered to tumor-bearing mice at 2-hour intervals, after which BNCT was carried out at the Massachusetts Institute of Technology (MIT) Research Reactor. Thirty days after BNCT, mice bearing TK1(+) L929 tumors had a 15× reduction in tumor volume compared with TK1(−) controls. Based on these favorable results, BNCT studies were then initiated in rats bearing intracerebral (i.c.) RG2 gliomas, after i.c. administration of N5–2OH by Alzet osmotic pumps, either alone or in combination with i.v. (i.v.) boronophenylalanine (BPA), a drug that has been used clinically. The mean survival times (MSTs) of RG2 glioma bearing rats were 45.6 ± 7.2 days, 35.0 ± 3.3days, and 52.9 ± 8.9 days, respectively, for animals that received N5–2OH, BPA, or both. The differences between the survival plots of rats that received N5–2OH and BPA alone were highly significant (P = 0.0003). These data provide proof-of-principle that a 3CTA can function as a boron delivery agent for NCT. Further studies are planned to design and synthesize 3CTAs with enhanced chemical and biological properties, and increased therapeutic efficacy. PMID:18981415

Using 171,173Yb(d,p) to benchmark a surrogate reaction for neutron capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatarik, R; Bersntein, L; Burke, J

2008-08-08

Neutron capture cross sections on unstable nuclei are important for many applications in nuclear structure and astrophysics. Measuring these cross sections directly is a major challenge and often impossible. An indirect approach for measuring these cross sections is the surrogate reaction method, which makes it possible to relate the desired cross section to a cross section of an alternate reaction that proceeds through the same compound nucleus. To benchmark the validity of using the (d,p{gamma}) reaction as a surrogate for (n,{gamma}), the {sup 171,173}Yb(d,p{gamma}) reactions were measured with the goal to reproduce the known [1] neutron capture cross section ratiosmore » of these nuclei.« less

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

PubMed

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

2016-05-01

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

The neutron flux monitors from 20 keV to 1 MeV for BNCT: performance study using accelerator-based neutron sources

NASA Astrophysics Data System (ADS)

Guan, X. C.; Gong, Y.; Murata, I.; Wang, T. S.

2018-05-01

The performance of the neutron flux monitors from 20 keV to 1 MeV developed for boron neutron capture therapy (BNCT) is studied by Monte Carlo simulations using accelerator-based neutron sources (ABNSs). The results show that the performance of the neutron flux monitors is very satisfactory and they can be efficiently used in practical applications to measure the neutron fluxes from 20 keV to 1 MeV of ABNSs for BNCT to high accuracy.

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

PubMed

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

2014-11-11

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

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

PubMed Central

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

2014-01-01

The application of boron neutron capture therapy (BNCT) mediated by liposomes containing 10B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70–88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70–88%. PMID:25349432

Analysis of boron distribution in vivo for boron neutron capture therapy using two different boron compounds by secondary ion mass spectrometry.

PubMed

Yokoyama, Kunio; Miyatake, Shin-Ichi; Kajimoto, Yoshinaga; Kawabata, Shinji; Doi, Atsushi; Yoshida, Toshiko; Okabe, Motonori; Kirihata, Mitsunori; Ono, Koji; Kuroiwa, Toshihiko

2007-01-01

The efficiency of boron neutron capture therapy (BNCT) for malignant gliomas depends on the selective and absolute accumulation of (10)B atoms in tumor tissues. Only two boron compounds, BPA and BSH, currently can be used clinically. However, the detailed distributions of these compounds have not been determined. Here we used secondary ion mass spectrometry (SIMS) to determine the histological distribution of (10)B atoms derived from the boron compounds BSH and BPA. C6 tumor-bearing rats were given 500 mg/kg of BPA or 100 mg/kg of BSH intraperitoneally; 2.5 h later, their brains were sectioned and subjected to SIMS. In the main tumor mass, BPA accumulated heterogeneously, while BSH accumulated homogeneously. In the peritumoral area, both BPA and BSH accumulated measurably. Interestingly, in this area, BSH accumulated distinctively in a diffuse manner even 800 microm distant from the interface between the main tumor and normal brain. In the contralateral brain, BPA accumulated measurably, while BSH did not. In conclusion, both BPA and BSH each have advantages and disadvantages. These compounds are considered to be essential as boron delivery agents independently for clinical BNCT. There is some rationale for the simultaneous use of both compounds in clinical BNCT for malignant gliomas.

Scissors Mode of 162 Dy Studied from Resonance Neutron Capture

DOE PAGES

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

2015-05-28

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

Final Report for the “WSU Neutron Capture Therapy Facility Support”

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerald E. Tripard; Keith G. Fox

2006-08-24

The objective for the cooperative research program for which this report has been written was to provide separate NCT facility user support for the students, faculty and scientists who would be doing the U.S. Department of Energy Office (DOE) of Science supported advanced radiotargeted research at the WSU 1 megawatt TRIGA reactor. The participants were the Idaho National laboratory (INL, P.I., Dave Nigg), the Veterinary Medical Research Center of Washington State University (WSU, Janean Fidel and Patrick Gavin), and the Washington State University Nuclear Radiation Center (WSU, P.I., Gerald Tripard). A significant number of DOE supported modifications were made tomore » the WSU reactor in order to create an epithermal neutron beam while at the same time maintaining the other activities of the 1 MW reactor. These modifications were: (1) Removal of the old thermal column. (2) Construction and insertion of a new epithermal filter, collimator and shield. (3) Construction of a shielded room that could accommodate the very high radiation field created by an intense neutron beam. (4) Removal of the previous reactor core fuel cluster arrangement. (5) Design and loading of the new reactor core fuel cluster arrangement in order to optimize the neutron flux entering the epithermal neutron filter. (6) The integration of the shielded rooms interlocks and radiological controls into the SCRAM chain and operating electronics of the reactor. (7) Construction of a motorized mechanism for moving and remotely controlling the position of the entire reactor bridge. (8) The integration of the reactor bridge control electronics into the SCRAM chain and operating electronics of the reactor. (9) The design, construction and attachment to the support structure of the reactor of an irradiation box that could be inserted into position next to the face of the reactor. (Necessitated by the previously mentioned core rearrangement). All of the above modifications were successfully completed and

Nuclear Structure of Rhenium-186 Revealed by Neutron-Capture Gamma Rays

DTIC Science & Technology

2014-03-01

σ0 [b] Reference 84(6) This Work 114(3) S. J. Friesenhahn [40] 112(2) S. F. Mughabghab [38] 100(8) H. Pomerance [41] 101(20) L. Seren [42] 116...41] H. Pomerance, "Thermal neutron capture cross sections," Phys. Rev., vol. 88, p. 412, 1952. [42] L. Seren , H. N. Friedlander and S. H. Turkel

Radiative capture of cold neutrons by protons and deuteron photodisintegration with twisted beams

NASA Astrophysics Data System (ADS)

Afanasev, Andrei; Serbo, Valeriy G.; Solyanik, Maria

2018-05-01

We consider two basic nuclear reactions: capture of neutrons by protons, n + p → γ + d, and its time-reversed counterpart, photodisintegration of the deuteron, γ + d → n + p. In both of these cases we assume that the incoming beam of neutrons or photons is ‘twisted’ by having an azimuthal phase dependence, i.e., it carries an additional angular momentum along its direction of propagation. Taking a low-energy limit of these reactions, we derive relations between corresponding transition amplitudes and cross sections with plane-wave beams and twisted beams. Implications for experiments with twisted cold neutrons and twisted photon beams are discussed.

Prompt gamma and neutron detection in BNCT utilizing a CdTe detector.

PubMed

Winkler, Alexander; Koivunoro, Hanna; Reijonen, Vappu; Auterinen, Iiro; Savolainen, Sauli

2015-12-01

In this work, a novel sensor technology based on CdTe detectors was tested for prompt gamma and neutron detection using boronated targets in (epi)thermal neutron beam at FiR1 research reactor in Espoo, Finland. Dedicated neutron filter structures were omitted to enable simultaneous measurement of both gamma and neutron radiation at low reactor power (2.5 kW). Spectra were collected and analyzed in four different setups in order to study the feasibility of the detector to measure 478 keV prompt gamma photons released from the neutron capture reaction of boron-10. The detector proved to have the required sensitivity to detect and separate the signals from both boron neutron and cadmium neutron capture reactions, which makes it a promising candidate for monitoring the spatial and temporal development of in vivo boron distribution in boron neutron capture therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy

PubMed Central

Wada, Yuki; Hirose, Katsumi; Harada, Takaomi; Sato, Mariko; Watanabe, Tsubasa; Anbai, Akira; Hashimoto, Manabu; Takai, Yoshihiro

2018-01-01

Abstract Boron neutron capture therapy (BNCT) can potentially deliver high linear energy transfer particles to tumor cells without causing severe damage to surrounding normal tissue, and may thus be beneficial for cases with characteristics of infiltrative growth, which need a wider irradiation field, such as glioblastoma multiforme. Hypoxia is an important factor contributing to resistance to anticancer therapies such as radiotherapy and chemotherapy. In this study, we investigated the impact of oxygen status on 10B uptake in glioblastoma cells in vitro in order to evaluate the potential impact of local hypoxia on BNCT. T98G and A172 glioblastoma cells were used in the present study, and we examined the influence of oxygen concentration on cell viability, mRNA expression of L-amino acid transporter 1 (LAT1), and the uptake amount of 10B-BPA. T98G and A172 glioblastoma cells became quiescent after 72 h under 1% hypoxia but remained viable. Uptake of 10B-BPA, which is one of the agents for BNCT in clinical use, decreased linearly as oxygen levels were reduced from 20% through to 10%, 3% and 1%. Hypoxia with <10% O2 significantly decreased mRNA expression of LAT1 in both cell lines, indicating that reduced uptake of 10B-BPA in glioblastoma in hypoxic conditions may be due to reduced expression of this important transporter protein. Hypoxia inhibits 10B-BPA uptake in glioblastoma cells in a linear fashion, meaning that approaches to overcoming local tumor hypoxia may be an effective method of improving the success of BNCT treatment. PMID:29315429

REVIEWS OF TOPICAL PROBLEMS: The theory of nucleosynthesis in stars: the slow neutron capture process

NASA Astrophysics Data System (ADS)

Chechev, Valerii P.; Kramarovskiĭ, Ya M.

1981-07-01

The theory of the s process of nucleosynthesis has received considerable development during recent years, mainly as the result of more detailed physical and mathematical treatments and also as a result of the accumulation of new observational data on stellar evolution and the abundance of the elements in the solar system, and accumulation of experimental data on neutron-capture cross sections. The exact solution of the s process equations obtained recently by Newman (1978) is discussed. It confirms the correctness of the initial s process theory (Clayton, Fowler, Hull, and Zimmerman, 1961). At the same time for small neutron exposures the exact and initial solutions differ. The influence of branching of the s-process due to competition between β decay and neutron capture is analyzed; it is noted that at a temperature ~3·108 K and a density of free neutrons 1.6·107 cm-3 the s process theory is in good agreement with observational data on the yields of the various nuclides. Models are discussed for the pulsed neutron s process, which leads to formation of heavy elements in the interior of a star as the result of periodic flares of the helium shell and subsequent remixing of the material.

Adjuvant neutron therapy in complex treatment of patients with locally advanced breast cancer

NASA Astrophysics Data System (ADS)

Lisin, V. A.; Velikaya, V. V.; Startseva, Zh. A.; Popova, N. O.; Goldberg, V. E.

2017-09-01

The study included 128 patients with stage T2-4N0-3M0 locally advanced breast cancer. All patients were divided into two groups. Group I (study group) consisted of 68 patients, who received neutron therapy, and group II (control group) comprised 60 patients, who received electron beam therapy. Neutron therapy was well tolerated by the patients and 1-2 grade radiation skin reactions were the most common. Neutron therapy was shown to be effective in multimodality treatment of the patients with locally advanced breast cancer. The 8-year recurrence-free survival rate in the patients with locally advanced breast cancer was 94.5 ± 4.1% after neutron therapy and 81.4 ± 5.9% after electron beam therapy (p = 0.05).

Status of the Neutron Capture Measurement on 237Np with the DANCE Array at LANSCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esch, E.-I.; Bond, E.M.; Bredeweg, T. A.

2005-05-24

Neptunium-237 is a major constituent of spent nuclear fuel. Estimates place the amount of 237Np bound for the Yucca Mountain high-level waste repository at 40 metric tons. The Department of Energy's Advanced Fuel Cycle Initiative program is evaluating methods for transmuting the actinide waste that will be generated by future operation of commercial nuclear power plants. The critical parameter that defines the transmutation efficiency of actinide isotopes is the neutron fission-to-capture ratio for the particular isotope in a given neutron spectrum. The calculation of transmutation efficiency therefore requires accurate fission and capture cross sections. Current 237Np evaluations available for transmutermore » system studies show significant discrepancies in both the fission and capture cross sections in the energy regions of interest. Herein we report on 237Np (n,{gamma}) measurements using the recently commissioned DANCE array.« less

Boron neutron capture therapy with bevacizumab may prolong the survival of recurrent malignant glioma patients: four cases

PubMed Central

2014-01-01

Background and importance Recurrent malignant gliomas (RMGs) are very difficult to control, and no standard treatments have been established for them. We performed boron neutron capture therapy (BNCT) for patients with RMG. BNCT enables high-dose particle radiation to be applied selectively to tumor cells. However, RMG cases generally receive nearly 60 Gy X-ray irradiation prior to re-irradiation by BNCT. Therefore, even with tumor-selective particle radiation BNCT, radiation necrosis in the brain and symptomatic pseudoprogression may develop. In four of our recent patients with RMG after BNCT, we applied the anti-VEGF antibody bevacizumab to treat two pathological entities. This approach appeared to prolong survival. Here we present the case reports of these four consecutive patients with RMG and discuss the novel use of bevacizumab in this context. Clinical presentation Four patients with RMGs were treated with BNCT at our institutes. Upon the referral for BNCT, they were assessed as belonging to the recursive partitioning analysis (RPA) class 3 (n = 3 patients) or RPA class 4 (n = 1 patient) (the RPA classification for RMG was advocated by Carson et al. in 2007). The estimated median survival times for RPA classes 3 and 4 were 3.8 and 10.8 months, respectively, after some treatment at the recurrence. We applied BNCT for these four patients and administered bevacizumab when the lesions were considered radiation necrosis or symptomatic pseudoprogression. The class 3 patients survived after the BNCT for 14, 16.5 and > 23 months, and the class 4 patient survived > 26 months, with favorable improvements in clinical symptoms. Conclusion BNCT with the addition of bevacizumab for radiation necrosis or symptomatic pseudoprogression improved the clinical symptoms and prolonged the survival in RMG patients. PMID:24387301

Neutron-capture rates for explosive nucleosynthesis: the case of 68Ni(n, γ) 69Ni

DOE PAGES

Spyrou, Artemis; Larsen, Ann-Cecilie; Liddick, Sean N.; ...

2017-02-22

Neutron-capture reactions play an important role in heavy element nucleosynthesis, since they are the driving force for the two processes that create the vast majority of the heavy elements. When a neutron capture occurs on a short-lived nucleus, it is extremely challenging to study the reaction directly and therefore the use of indirect techniques is essential. The present work reports on such an indirect measurement that provides strong constraints on the 68Ni(n,g) 69Ni reaction rate.The commonly used reaction libraries JINA-REACLIB and BRUSLIB are in relatively good agreement with the experimental rate. The impact of the new rate on weak r-processmore » calculations is discussed.« less

Thermal neutron radiative capture cross-section of 186W(n, γ)187W reaction

NASA Astrophysics Data System (ADS)

Tan, V. H.; Son, P. N.

2016-06-01

The thermal neutron radiative capture cross section for 186W(n, γ)187W reaction was measured by the activation method using the filtered neutron beam at the Dalat research reactor. An optimal composition of Si and Bi, in single crystal form, has been used as neutron filters to create the high-purity filtered neutron beam with Cadmium ratio of Rcd = 420 and peak energy En = 0.025 eV. The induced activities in the irradiated samples were measured by a high resolution HPGe digital gamma-ray spectrometer. The present result of cross section has been determined relatively to the reference value of the standard reaction 197Au(n, γ)198Au. The necessary correction factors for gamma-ray true coincidence summing, and thermal neutron self-shielding effects were taken into account in this experiment by Monte Carlo simulations.

Compact D-D Neutron Source-Driven Subcritical Multiplier and Beam-Shaping Assembly for Boron Neutron Capture Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Francesco Ganda; Jasmina Vujic; Ehud Greenspan

2010-12-01

This work assesses the feasibility of using a small, safe, and inexpensive keff 0.98 subcritical fission assembly [subcritical neutron multiplier (SCM)] to amplify the treatment neutron beam intensity attainable from a compact deuterium-deuterium (D-D) fusion neutron source delivering [approximately]1012 n/s. The objective is to reduce the treatment time for deep-seated brain tumors to [approximately]1 h. The paper describes the optimal SCM design and two optimal beam-shaping assemblies (BSAs) - one designed to maximize the dose rate and the other designed to maximize the total dose that can be delivered to a deep-seated tumor. The neutron beam intensity amplification achieved withmore » the optimized SCM and BSA results in an increase in the treatment dose rate by a factor of 18: from 0.56 Gy/h without the SCM to 10.1 Gy/h. The entire SCM is encased in an aluminum structure. The total amount of 20% enriched uranium required for the SCM is 8.5 kg, and the cost (not including fabrication) is estimated to be less than $60,000. The SCM power level is estimated at 400 W when driven by a 1012 n/s D-D neutron source. This translates into consumption of only [approximately]0.6% of the initially loaded 235U atoms during 50 years of continuous operation and implies that the SCM could operate continuously for the entire lifetime of the facility without refueling. Cooling the SCM does not pose a challenge; it may be accomplished by natural circulation as the maximum heat flux is only 0.034 W/cm2.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Ling-Wei, E-mail: lwwang@vghtpe.gov.tw; National Yang-Ming University, Taiwan; Chen, Yi-Wei

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

Thermal neutron capture cross sections for 16,171,18O and 2H

NASA Astrophysics Data System (ADS)

Firestone, R. B.; Revay, Zs.

2016-04-01

Thermal neutron capture γ -ray spectra for 16,17,18O and 2H have been measured with guided cold neutron beams from the Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II) reactor and the Budapest Research Reactor (BRR) on natural and O,1817 enriched D2O targets. Complete neutron capture γ -ray decay schemes for the 16,17,18O(n ,γ ) reactions were measured. Absolute transition probabilities were determined for each reaction by a least-squares fit of the γ -ray intensities to the decay schemes after accounting for the contribution from internal conversion. The transition probability for the 870.76-keV γ ray from 16O(n ,γ ) was measured as Pγ(871 )=96.6 ±0.5 % and the thermal neutron cross section for this γ ray was determined as 0.164 ±0.003 mb by internal standardization with multiple targets containing oxygen and stoichiometric quantities of hydrogen, nitrogen, and carbon whose γ -ray cross sections were previously standardized. The γ -ray cross sections for the O,1817(n ,γ ) and 2H(n ,γ ) reactions were then determined relative to the 870.76-keV γ -ray cross section after accounting for the isotopic abundances in the targets. We determined the following total radiative thermal neutron cross sections for each isotope from the γ -ray cross sections and transition probabilities; σ0(16O )=0.170 ±0.003 mb; σ0(17O )=0.67 ±0.07 mb; σ0(18O )=0.141 ±0.006 mb; and σ0(2H )=0.489 ±0.006 mb.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, D; Jung, J; Suh, T

2014-06-01

Purpose: Purpose of paper is to confirm the feasibility of acquisition of three dimensional single photon emission computed tomography (SPECT) image from boron neutron capture therapy (BNCT) using Monte Carlo simulation. Methods: In case of simulation, the pixelated SPECT detector, collimator and phantom were simulated using Monte Carlo n particle extended (MCNPX) simulation tool. A thermal neutron source (<1 eV) was used to react with the boron uptake region (BUR) in the phantom. Each geometry had a spherical pattern, and three different BURs (A, B and C region, density: 2.08 g/cm3) were located in the middle of the brain phantom.more » 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

Preparation of a one-curie 171Tm target for the Detector for Advanced Neutron Capture Experiments (DANCE)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwantes, Jon M.; Taylor, Wayne A.; Rundberg, Robert S.

2008-05-15

Roughly one curie of 171Tm (t1/2=1.92a) has been produced and purified for the purpose of making a nuclear target for the first measurements of its neutron capture cross section. Target preparation consisted of three key steps: (1) material production; (2) separation and purification; and (3) electrodeposition onto a suitable backing material. Approximately 1.5 mg of the target material (at the time of separation) was produced by irradiating roughly 250 mg of its stable enriched 170Er lanthanide neighbor with neutrons at the ILL reactor in France. This production method resulted in a “difficult-to-separate” 1:167 mixture of near-neighboring lanthanides, Tm and Er.more » Separation and purification was accomplished using high-performance liquid chromatorgraphy (HPLC), with a proprietary cation exchange column (Dionex, CS-3) and alpha-hydroxyisobutyric acid (a-HIB) eluent. This technique yielded a final product of ~95% purity with respect to Tm. A portion (20 ug) of the Tm was electrodeposited on thin Be foil and delivered to the Los Alamos Neutron Science CEnter (LANSCE) for preliminary analysis of its neutron capture cross section using the Detector for Advanced Neutron Capture Experiments (DANCE). This paper discusses the major hurdles associated with the separation and purification step including, scale-up issues related to the use of HPLC for material separation and purification of the target material from a-HIB and 4-(2-pyridylazo)resorcinol (PAR) colorant.« less

Development of An Epi-thermal Neutron Field for Fundamental Researches for BNCT with A DT Neutron Source

NASA Astrophysics Data System (ADS)

Osawa, Yuta; Imoto, Shoichi; Kusaka, Sachie; Sato, Fuminobu; Tanoshita, Masahiro; Murata, Isao

2017-09-01

Boron Neutron Capture Therapy (BNCT) is known to be a new promising cancer therapy suppressing influence against normal cells. In Japan, Accelerator Based Neutron Sources (ABNS) are being developed for BNCT. For the spread of ABNS based BNCT, we should characterize the neutron field beforehand. For this purpose, we have been developing a low-energy neutron spectrometer based on 3He position sensitive proportional counter. In this study, a new intense epi-thermal neutron field was developed with a DT neutron source for verification of validity of the spectrometer. After the development, the neutron field characteristics were experimentally evaluated by using activation foils. As a result, we confirmed that an epi-thermal neutron field was successfully developed suppressing fast neutrons substantially. Thereafter, the neutron spectrometer was verified experimentally. In the verification, although a measured detection depth distribution agreed well with the calculated distribution by MCNP, the unfolded spectrum was significantly different from the calculated neutron spectrum due to contribution of the side neutron incidence. Therefore, we designed a new neutron collimator consisting of a polyethylene pre-collimator and boron carbide neutron absorber and confirmed numerically that it could suppress the side incident neutrons and shape the neutron flux to be like a pencil beam.

A Gamma Polarimeter for Neutron Polarization Measurement in a Liquid Deuterium Target for Parity Violation in Polarized Neutron Capture on Deuterium.

PubMed

Komives, A; Sint, A K; Bowers, M; Snow, M

2005-01-01

A measurement of the parity-violating gamma asymmetry in n-D capture would yield information on N-N parity violation independent of the n-p system. Since cold neutrons will depolarize in a liquid deuterium target in which the scattering cross section is much larger than the absorption cross section, it will be necessary to quantify the loss of polarization before capture. One way to do this is to use the large circular polarization of the gamma from n-D capture and analyze the circular polarization of the gamma in a gamma polarimeter. We describe the design of this polarimeter.

BINP accelerator based epithermal neutron source.

PubMed

Aleynik, V; Burdakov, A; Davydenko, V; Ivanov, A; Kanygin, V; Kuznetsov, A; Makarov, A; Sorokin, I; Taskaev, S

2011-12-01

Innovative facility for neutron capture therapy has been built at BINP. This facility is based on compact vacuum insulation tandem accelerator designed to produce proton current up to 10 mA. Epithermal neutrons are proposed to be generated by 1.915-2.5 MeV protons bombarding a lithium target using (7)Li(p,n)(7)Be threshold reaction. In the article, diagnostic techniques for proton beam and neutrons developed are described, results of experiments on proton beam transport and neutron generation are shown, discussed, and plans are presented. Copyright © 2011 Elsevier Ltd. All rights reserved.

Measurement of the neutron capture resonances for platinum using the Ge spectrometer and pulsed neutron beam at the J-PARC/MLF/ANNRI

NASA Astrophysics Data System (ADS)

Kino, Koichi; Hasemi, Hiroyuki; Kimura, Atsushi; Kiyanagi, Yoshiaki

2017-09-01

The neutron capture cross-section for platinum was measured at J-PARC/MLF/ANNRI. The intense pulsed neutron beam was impinging on a natural platinum foil sample and the emitted prompt γ-rays were detected by a Ge spectrometer. The peak energies of the low energy resonances for natural platinum are consistent with those of the JEFF-3.1.2, RUSFOND2010 and next-JENDL data libraries except for the 20-eV resonance. The resonance cross-sections of the next-JENDL library do not contradict the present measurements within the uncertainty of the absolute value of the present work. We analysed the prompt γ-ray spectrum and found a clear 7921.93 keV peak that originates from the transition from the 196Pt compound state to its ground state. The neutron capture cross-section for 195Pt was obtained by choosing events of this peak. The peak energies of most of the low energy resonances are almost consistent with those of the RUSFOND2010 and next-JENDL libraries. However, there was a disagreement for the 20-eV resonance.

The Universality of the Rapid Neutron-capture Process Revealed by a Possible Disrupted Dwarf Galaxy Star

NASA Astrophysics Data System (ADS)

Casey, Andrew R.; Schlaufman, Kevin C.

2017-12-01

The rapid neutron-capture or r-process is thought to produce the majority of the heavy elements (Z> 30) in extremely metal-poor stars. The same process is also responsible for a significant fraction of the heavy elements in the Sun. This universality of the r-process is one of its characteristic features, as well as one of the most important clues to its astrophysical origin. We report the discovery of an extremely metal-poor field giant with [{Sr},{Ba}/{{H}}]≈ -6.0 and [{Sr},{Ba}/{Fe}]≈ -3.0, the lowest abundances of strontium and barium relative to iron ever observed. Despite its low abundances, the star 2MASS J151113.24-213003.0 has [{Sr}/{Ba}]=-0.11+/- 0.14, therefore its neutron-capture abundances are consistent with the main solar r-process pattern that has [{Sr}/{Ba}]=-0.25. It has been suggested that extremely low neutron-capture abundances are a characteristic of dwarf galaxies, and we find that this star is on a highly eccentric orbit with an apocenter ≳100 kpc that lies in the disk of satellites in the halo of the Milky Way. We show that other extremely metal-poor stars with low [Sr, Ba/H] and [Sr, Ba/Fe] plus solar [Sr/Ba] tend to have orbits with large apocenters, consistent with a dwarf galaxy origin for this class of object. The nucleosynthesis event that produced the neutron-capture elements in 2MASS J151113.24-213003.0 must produce both strontium and barium together in the solar ratio. We exclude contributions from the s-process in intermediate-mass asymptotic giant branch or fast-rotating massive metal-poor stars, pair-instability supernovae, the weak r-process, and neutron-star mergers. We argue that the event was a Pop III or extreme Pop II core-collapse supernova explosion. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

Measurement of the 242Pu neutron capture cross section

NASA Astrophysics Data System (ADS)

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

2015-10-01

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

Neutron Capture Cross Section of Unstable Ni63: Implications for Stellar Nucleosynthesis

NASA Astrophysics Data System (ADS)

Lederer, C.; Massimi, C.; Altstadt, S.; Andrzejewski, J.; Audouin, L.; Barbagallo, M.; Bécares, V.; Bečvář, F.; Belloni, F.; Berthoumieux, E.; Billowes, J.; Boccone, V.; Bosnar, D.; Brugger, M.; Calviani, M.; Calviño, F.; Cano-Ott, D.; Carrapiço, C.; Cerutti, F.; Chiaveri, E.; Chin, M.; Colonna, N.; Cortés, G.; Cortés-Giraldo, M. A.; Diakaki, M.; Domingo-Pardo, C.; Duran, I.; Dressler, R.; Dzysiuk, N.; Eleftheriadis, C.; Ferrari, A.; Fraval, K.; Ganesan, S.; García, A. R.; Giubrone, G.; Gómez-Hornillos, M. B.; Gonçalves, I. F.; González-Romero, E.; Griesmayer, E.; Guerrero, C.; Gunsing, F.; Gurusamy, P.; Jenkins, D. G.; Jericha, E.; Kadi, Y.; Käppeler, F.; Karadimos, D.; Kivel, N.; Koehler, P.; Kokkoris, M.; Korschinek, G.; Krtička, M.; Kroll, J.; Langer, C.; Leeb, H.; Leong, L. S.; Losito, R.; Manousos, A.; Marganiec, J.; Martínez, T.; Mastinu, P. F.; Mastromarco, M.; Meaze, M.; Mendoza, E.; Mengoni, A.; Milazzo, P. M.; Mingrone, F.; Mirea, M.; Mondelaers, W.; Paradela, C.; Pavlik, A.; Perkowski, J.; Pignatari, M.; Plompen, A.; Praena, J.; Quesada, J. M.; Rauscher, T.; Reifarth, R.; Riego, A.; Roman, F.; Rubbia, C.; Sarmento, R.; Schillebeeckx, P.; Schmidt, S.; Schumann, D.; Tagliente, G.; Tain, J. L.; Tarrío, D.; Tassan-Got, L.; Tsinganis, A.; Valenta, S.; Vannini, G.; Variale, V.; Vaz, P.; Ventura, A.; Versaci, R.; Vermeulen, M. J.; Vlachoudis, V.; Vlastou, R.; Wallner, A.; Ware, T.; Weigand, M.; Weiß, C.; Wright, T. J.; Žugec, P.

2013-01-01

The Ni63(n,γ) cross section has been measured for the first time at the neutron time-of-flight facility n_TOF at CERN from thermal neutron energies up to 200 keV. In total, capture kernels of 12 (new) resonances were determined. Maxwellian averaged cross sections were calculated for thermal energies from kT=5-100keV with uncertainties around 20%. Stellar model calculations for a 25M⊙ star show that the new data have a significant effect on the s-process production of Cu63, Ni64, and Zn64 in massive stars, allowing stronger constraints on the Cu yields from explosive nucleosynthesis in the subsequent supernova.

Neutron capture cross-section measurements for 238U between 0.4 and 1.4 MeV

NASA Astrophysics Data System (ADS)

Krishichayan, Fnu; Finch, S. W.; Howell, C. R.; Tonchev, A. P.; Tornow, W.

2017-09-01

Neutron-induced radiative-capture cross-section data of 238U are crucial for fundamental nuclear physics as well as for Stewardship Science, for advanced-fuel-cycle calculations, and for nuclear astrophysics. Based on different techniques, there are a large number of 238U(n, γ) 239U cross-section data available in the literature. However, there is a lack of systematic and consistent measurements in the 0.1 to 3.0 MeV energy range. The goal of the neutron-capture project at TUNL is to provide accurate 238U(n, γ) 239U cross-section data in this energy range. The 238U samples, sandwiched between gold foils of the same size, were irradiated for 8-14 hours with monoenergetic neutrons. To avoid any contribution from thermal neutrons, the 238U and 197Au targets were placed inside of a thin-walled pill-box made of 238U. Finally, the whole pill-box was wrapped in a gold foil as well. After irradiation, the samples were gamma-counted at the TUNL's low-background counting facility using high-efficient HPGe detectors. The 197Au monitor foils were used to calculate the neutron flux. The experimental technique and 238U(n, γ) 239U cross-section results at 6 energies will be discussed during the meeting.

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

NASA Astrophysics Data System (ADS)

Sztejnberg Goncalves-Carralves, Manuel Leonardo

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

Characteristics and application of spherical-type activation detectors in neutron spectrum measurements at a boron neutron capture therapy (BNCT) facility

NASA Astrophysics Data System (ADS)

Lin, Heng-Xiao; Chen, Wei-Lin; Liu, Yuan-Hao; Sheu, Rong-Jiun

2016-03-01

A set of spherical-type activation detectors was developed aiming to provide better determination of the neutron spectrum at the Tsing Hua Open-pool Reactor (THOR) BNCT facility. An activation foil embedded in a specially designed spherical holder exhibits three advantages: (1) minimizing the effect of neutron angular dependence, (2) creating response functions with broadened coverage of neutron energies by introducing additional moderators or absorbers to the central activation foil, and (3) reducing irradiation time because of improved detection efficiencies to epithermal neutron beam. This paper presents the design concept and the calculated response functions of new detectors. Theoretical and experimental demonstrations of the performance of the detectors are provided through comparisons of the unfolded neutron spectra determined using this method and conventional multiple-foil activation techniques.

FUSE Observations of Neutron-Capture Elements in Wolf-Rayet Planetary Nebulae

NASA Astrophysics Data System (ADS)

Dinerstein, H.

We propose to obtain FUSE observations of planetary nebula central stars of the WC Wolf-Rayet ([WC]) class, in order to search for the products of neutron-capture processes in these stars and provide constraints on their evolutionary status. Although the origin of the [WC]'s is controversial, their H-deficient, C-rich surface compositions indicate that they have experienced a high degree of mixing and/or mass loss. Thus one might expect the nebulae they produce to show enhanced concentrations of He-burning and other nuclear products, such as nuclei produced by slow neutron capture during the AGB phase. We have already detected an absorption line from one such element, Germanium (Sterling, Dinerstein, & Bowers 2002), while conducting a search for H2 absorption from nebular molecular material FUSE GI programs A085 and B069). Since the strongest Ge enhancements were found in PNe with [WC] central stars, we propose to enlarge the sample of such objects observed by FUSE. THIS TEMPORARY AND PARTIAL SCRIPT COVERS ONE TARGET, HE 2-99, AND REQUESTS AN EXPOSURE TIME OF 15 KSEC. PHASE 2 INFORMATION FOR THE REMAINDER OF THE PROGRAM'S TOTAL TIME ALLOCATION OF 60 KSEC WILL BE SUBMITTED AT A LATER TIME.

Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy

PubMed Central

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

2012-01-01

Objectives To evaluate the effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a 10B–carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT. Conclusion BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases. PMID:22391496

The Open Cluster Chemical Abundances and Mapping (OCCAM) Survey: Optical Extension for Neutron Capture Elements

NASA Astrophysics Data System (ADS)

Melendez, Matthew; O'Connell, Julia; Frinchaboy, Peter M.; Donor, John; Cunha, Katia M. L.; Shetrone, Matthew D.; Majewski, Steven R.; Zasowski, Gail; Pinsonneault, Marc H.; Roman-Lopes, Alexandre; Stassun, Keivan G.; APOGEE Team

2017-01-01

The Open Cluster Chemical Abundance & Mapping (OCCAM) survey is a systematic survey of Galactic open clusters using data primarily from the SDSS-III/APOGEE-1 survey. However, neutron capture elements are very limited in the IR region covered by APOGEE. In an effort to fully study detailed Galactic chemical evolution, we are conducting a high resolution (R~60,000) spectroscopic abundance analysis of neutron capture elements for OCCAM clusters in the optical regime to complement the APOGEE results. As part of this effort, we present Ba II, La II, Ce II and Eu II results for a few open clusters without previous abundance measurements using data obtained at McDonald Observatory with the 2.1m Otto Struve telescope and Sandiford Echelle Spectrograph.This work is supported by an NSF AAG grant AST-1311835.

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

PubMed

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.

Progress Towards an Indirect Neutron Capture Capability at LANSCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koehler, Paul E.; Ullmann, John Leonard; Couture, Aaron Joseph

2017-09-20

There are many neutron-capture cross sections of importance to radiochemical diagnostics and nuclear forensics which are beyond the reach of direct measurements. Hence, we have been developing an apparatus on flight path (FP) 13 at target 1 at LANSCE for tightly constraining these cross sections via determination of the underlying physical quantities. FP-13 was initially a cold-neutron beam line for materials science and therefore required substantial modification for use for nuclear physics. In FY17, we made several improvements to FP-13, demonstrated improved performance due to these changes via measurements on a variety of samples, identified a few more needed improvements,more » and reconfigured the beam line to implement the most important of these. New measurements to assess the impact of the most recent improvement will commence when beam is restored to LANSCE. Although FP-13 has not yet reached the performance required for small radioactive samples, measurements on a gold sample have led to an important science result which we are preparing for publication.« less

Neutron radiative capture cross section of Cu,6563 between 0.4 and 7.5 MeV

NASA Astrophysics Data System (ADS)

Newsome, I.; Bhike, M.; Krishichayan, Tornow, W.

2018-04-01

Natural copper is commonly used as cooling and shielding medium in detector arrangements designed to search for neutrinoless double-β decay. Neutron-induced background reactions on copper could potentially produce signals that are indistinguishable from the signals of interest. The present work focuses on radiative neutron capture experiments on Cu,6563 in the 0.4 to 7.5 MeV neutron energy range. The new data provide evaluations and model calculations with benchmark data needed to extend their applicability in predicting background rates in neutrinoless double-β decay experiments.

Commissioning optically stimulated luminescence in vivo dosimeters for fast neutron therapy.

PubMed

Young, Lori A; Yang, Fei; Woodworth, Davis; McCormick, Zephyr; Sandison, George

2016-01-01

Clinical in vivo dosimeters intended for use with photon and electron therapies have not been utilized for fast neutron therapy because they are highly susceptible to neutron damage. The objective of this work was to determine if a commercial optically stimulated luminescence (OSL) in vivo dosimetry system could be adapted for use in fast neutron therapy. A 50.5 MeV fast neutron beam generated by a clinical neutron therapy cyclotron was used to irradiate carbon doped aluminum oxide (Al2O3:C) optically simulated luminescence dosimeters (OSLDs) in a solid water phantom under standard calibration conditions, 150 cm SAD, 1.7 cm depth, and 10.3 × 10.0 cm field size. OSLD fading and electron trap depletion studies were performed with the OSLDs irradiated with 20 and 50 cGy and monitored over a 24-h period to determine the optimal time for reading the dosimeters during calibration. Four OSLDs per group were calibrated over a clinical dose range of 0-150 cGy. OSLD measurement uncertainties were lowered to within ±2%-3% of the expected dose by minimizing the effect of transient fading that occurs with neutron irradiation and maintaining individual calibration factors for each dosimeter. Dose dependent luminescence fading extended beyond the manufacturer's recommended 10 min period for irradiation with photon or electron beams. To minimize OSL variances caused by inconsistent fading among dosimeters, the observed optimal time for reading the OSLDs postirradiation was between 30 and 90 min. No field size, wedge factor, or gantry angle dependencies were observed in the OSLDs irradiated by the studied fast neutron beam. Measurements demonstrated that uncertainties less than ±3% were attainable in OSLDs irradiated with fast neutrons under clinical conditions. Accuracy and precision comparable to clinical OSL measurements observed with photons can be achieved by maintaining individual OSLD calibration factors and minimizing transient fading effects.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1999-09-01

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 clinicalmore » 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

Detector-Response Correction of Two-Dimensional γ -Ray Spectra from Neutron Capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusev, G.; Jandel, M.; Arnold, C. W.

2015-05-28

The neutron-capture reaction produces a large variety of γ-ray cascades with different γ-ray multiplicities. A measured spectral distribution of these cascades for each γ-ray multiplicity is of importance to applications and studies of γ-ray statistical properties. The DANCE array, a 4π ball of 160 BaF 2 detectors, is an ideal tool for measurement of neutron-capture γ-rays. The high granularity of DANCE enables measurements of high-multiplicity γ-ray cascades. The measured two-dimensional spectra (γ-ray energy, γ-ray multiplicity) have to be corrected for the DANCE detector response in order to compare them with predictions of the statistical model or use them in applications.more » The detector-response correction problem becomes more difficult for a 4π detection system than for a single detector. A trial and error approach and an iterative decomposition of γ-ray multiplets, have been successfully applied to the detector-response correction. As a result, applications of the decomposition methods are discussed for two-dimensional γ-ray spectra measured at DANCE from γ-ray sources and from the 10B(n, γ) and 113Cd(n, γ) reactions.« less

Uptake and metabolism of boronophenylalanine in human uveal melanoma cells in culture Relevance to boron neutron capture therapy of cancer cells.

PubMed

Belkhou, R; Abbé, J C; Pham, P; Jasner, N; Sahel, J; Dreyfus, H; Moutaouakkil, M; Massarelli, R

1995-06-01

The transport of boronophenylalanine (BPA) and its metabolic fate have been studied in a human uveal melanoma cell line isolated from a primary enucleated tumor. The boronated compound was rapidly incorporated into the cells reaching a peak of incorporation in two hours. This was followed by a trough between 10 and 24 hours and by an increase thereafter. The analogy with the amino acids phenylalanine (Phe) and tyrosine (Tyr) was studied in competition experiments incubating cultures of cell line MK-T, isolated in this laboratory, with [(3)H]-Phe and [(125)I]-Tyr, in the presence or absence of various concentrations of BPA, between 0 and 5 min. The presence of BPA severely reduced the uptake of both amino acids. The kinetics of the transport of [(3)H]-Phe and [(3)H]-Tyr in the presence of BPA, measured after 10 sec of incubation, showed that the boronated compound exerted a competitive inhibition on both transport systems. The intracellular metabolism of BPA was followed by measuring boron concentration (measured with Ionization Coupled Mass Spectrometry) in subcellular fractions and after membrane extraction by the detergent Triton X-100. The results showed that BPA remained in the supernatant and was not metabolized into macromolecules. These results and the relative absence of melanine in these cells, as observed by electron microscopy, suggest that BPA may be actively transported into melanoma cells but not metabolized. The results may have a relevance in studies on Boron Neutron Capture Therapy.

γ{\\hbox-}Flash suppression using a gated photomultiplier assembled with an LaBr3(Ce) detector to measure fast neutron capture reactions

NASA Astrophysics Data System (ADS)

Hara, K. Y.; Harada, H.; Toh, Y.; Hori, J.

2013-09-01

A gated photomultiplier tube (PMT) assembled with an LaBr3(Ce) detector was applied toward the prompt γ{hbox-}ray measurement of fast neutron capture reactions. Time-of-flight measurements of the neutron capture reactions of Cl and Al were performed using the 46-MeV electron linear accelerator at the Kyoto University Research Reactor Institute (KURRI) as a pulsed neutron source. The photomultiplier gating technique effectively suppressed the saturation of the PMT output and extended the energy region of the TOF measurement.

Capture cross sections on unstable nuclei

NASA Astrophysics Data System (ADS)

Tonchev, A. P.; Escher, J. E.; Scielzo, N.; Bedrossian, P.; Ilieva, R. S.; Humby, P.; Cooper, N.; Goddard, P. M.; Werner, V.; Tornow, W.; Rusev, G.; Kelley, J. H.; Pietralla, N.; Scheck, M.; Savran, D.; Löher, B.; Yates, S. W.; Crider, B. P.; Peters, E. E.; Tsoneva, N.; Goriely, S.

2017-09-01

Accurate neutron-capture cross sections on unstable nuclei near the line of beta stability are crucial for understanding the s-process nucleosynthesis. However, neutron-capture cross sections for short-lived radionuclides are difficult to measure due to the fact that the measurements require both highly radioactive samples and intense neutron sources. Essential ingredients for describing the γ decays following neutron capture are the γ-ray strength function and level densities. We will compare different indirect approaches for obtaining the most relevant observables that can constrain Hauser-Feshbach statistical-model calculations of capture cross sections. Specifically, we will consider photon scattering using monoenergetic and 100% linearly polarized photon beams. Challenges that exist on the path to obtaining neutron-capture cross sections for reactions on isotopes near and far from stability will be discussed.

The Open Cluster Chemical Abundances and Mapping (OCCAM) Survey: Galactic Neutron Capture Abundance Gradients

NASA Astrophysics Data System (ADS)

O'Connell, Julia; Frinchaboy, Peter M.; Shetrone, Matthew D.; Melendez, Matthew; Cunha, Katia M. L.; Majewski, Steven R.; Zasowski, Gail; APOGEE Team

2017-01-01

The evolution of elements, as a function or age, throughout the Milky Way disk provides a key constraint for galaxy evolution models. In an effort to provide these constraints, we have conducted an investigation into the r- and s- process elemental abundances for a large sample of open clusters as part of an optical follow-up to the SDSS-III/APOGEE-1 survey. Stars were identified as cluster members by the Open Cluster Chemical Abundance & Mapping (OCCAM) survey, which culls member candidates by radial velocity, metallicity, and proper motion from the observed APOGEE sample. To obtain data for neutron capture elements in these clusters, we conducted a long-term observing campaign covering three years (2013-2016) using the McDonald Observatory Otto Struve 2.1-m telescope and Sandiford Cass Echelle Spectrograph (R ~ 60,000). We present Galactic neutron-capture abundance gradients using 30+ clusters, within 6 kpc of the Sun, covering a range of ages from ~80 Myr to ~10 Gyr .

The Open Cluster Chemical Abundances and Mapping (OCCAM) Survey: Galactic Neutron CaptureAbundance Gradients

NASA Astrophysics Data System (ADS)

O'Connell, Julia; Frinchaboy, Peter M.; Shetrone, Matthew D.; Melendez, Matthew; Cunha, Katia; Majewski, Steven R.; Zasowski, Gail; APOGEE Team

2017-06-01

The evolution of elements, as a function or age, throughout the Milky Way disk provides a key constraint for galaxy evolution models. In an effort to provide these constraints, we have conducted an investigation into the r- and s- process elemental abundances for a large sample of open clusters as part of an optical follow-up to the SDSS-III/APOGEE-1 survey. Stars were identified as cluster members by the Open Cluster Chemical Abundance & Mapping (OCCAM) survey, which culls member candidates by radial velocity, metallicity and proper motion from the observed APOGEE sample. To obtain data for neutron capture elements in these clusters, we conducted a long-term observing campaign covering three years (2013-2016) using the McDonald Observatory Otto Struve 2.1-m telescope and Sandiford Cass Echelle Spectrograph (R ~ 60,000). We present Galactic neutron capture abundance gradients using 30+ clusters, within 6 kpc of the Sun, covering a range of ages from ~80 Myr to ~10 Gyr .

Neutron Capture Cross Sections of the s-Process Branching Points 147Pm, 171Tm, and 204Tl

NASA Astrophysics Data System (ADS)

Guerrero, Carlos; Domingo-Pardo, Cesar; Lerendegui-Marco, Jorge; Casanovas, Adria; Cortes-Giraldo, Miguel A.; Dressler, Rugard; Halfon, Shlomi; Heinitz, Stephan; Kivel, Niko; Köster, Ulli; Paul, Michael; Quesada-Molina, Jose Manuel; Schumann, Dorothea; Tarifeño-Saldivia, Ariel; Tessler, Moshe; Weissman, Leo

The neutron capture cross section of several key unstable isotopes acting as branching points in the s-process are crucial for stellar nucleosynthesis studies, but they are very challenging to measure due to the difficult production of sufficient sample material, the high activity of the resulting samples, and the actual (n, γ) measurement, for which high neutron fluxes and effective background rejection capabilities are required. As part of a new program to measure some of these important branching points, radioactive targets of 147Pm, 171Tm, and 204Tl have been produced by irradiation of stable isotopes (146Nd, 170Er, and 203Tl) at the Institut Laue-Langevin (ILL) high flux reactor. After breeding in the reactor and a certain cooling period, the resulting mixed 204Tl/203Tl sample was used directly while 147Pm and 171Tm were radiochemically separated in non-carrier-added quality at the Paul Scherrer Institut (PSI), then prepared as targets. A set of theses samples has been used for time-of-flight measurements at the CERN n_TOF facility using the 19 and 185 m beam lines, during 2014 and 2015. The capture cascades were detected with a set of four C6D6 scintillators, allowing to observe the associated neutron capture resonances. The results presented in this work are the first ever determination of the resonance capture cross sections of 147Pm, 171Tm, and 204Tl. Activation experiments on the same 147Pm and 171Tm targets with a high-intensity quasi-Maxwellian flux of neutrons have been performed using the SARAF accelerator and the Liquid-Lithium Target (LiLiT) in order to extract the corresponding Maxwellian Average Cross Section (MACS). The experimental setups are here described together with the first, preliminary results of the n_TOF measurement.

In vivo neutron activation analysis of sodium and chlorine in tumor tissue after fast neutron therapy.

PubMed

Auberger, T; Koester, L; Knopf, K; Weissfloch, L

1996-01-01

In 12 patients with recurrences and metastases of different primaries (head and neck cancer, breast cancer, malignant melanoma, and osteosarcoma) who were treated with reactor fission neutrons the photon emission of irradiated tissue was measured after each radiotherapy fraction. Spectral analyses of the decay rates resulted in data for the exchange of sodium (Na) and chlorine (Cl) between the irradiated tissue and the body. About 60% of Na and Cl exchanged rapidly with a turnover half-life of 13 +/- 2 min. New defined mass exchange rates for Na and Cl amount to an average of 0.8 mval/min/kg of soft tissue. At the beginning of radiotherapy the turnover of the electrolytes in tissues with large tumor volumes was about twice that in tissues with small tumor volumes. Depending on the dose, neutron therapy led in all cases to variation in the metabolism. A maximum of Cl exchange and a minimum of Na exchange occurred after 10 Gy of neutrons (group of six previously untreated patients) or after 85 Gy (photon equivalent dose) of combined photon-neutron therapy. A significant increase in non-exchangeable fraction of Na from about 40 to 80% was observed in three tumors after a neutron dose of 10 Gy administered in five fractions correlated with a rapid reduction of tissue within 4 weeks after end of therapy. These results demonstrate for the first time the local response of the electrolyte metabolism to radiotherapy.

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Grazing-Incidence Neutron Optics based on Wolter Geometries

NASA Technical Reports Server (NTRS)

Gubarev, M. V.; Ramsey, B. D.; Mildner, D. F. R.

2008-01-01

The feasibility of grazing-incidence neutron imaging optics based on the Wolter geometries have been successfully demonstrated. Biological microscopy, neutron radiography, medical imaging, neutron crystallography and boron neutron capture therapy would benefit from high resolution focusing neutron optics. Two bounce optics can also be used to focus neutrons in SANS experiments. Here, the use of the optics would result in lower values of obtainable scattering angles. The high efficiency of the optics permits a decrease in the minimum scattering vector without lowering the neutron intensity on sample. In this application, a significant advantage of the reflective optics over refractive optics is that the focus is independent of wavelength, so that the technique can be applied to polychromatic beams at pulsed neutron sources.

Capture cross sections on unstable nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tonchev, A. P.; Escher, J. E.; Scielzo, N.

2017-09-13

Accurate neutron-capture cross sections on unstable nuclei near the line of beta stability are crucial for understanding the s-process nucleosynthesis. However, neutron-capture cross sections for short-lived radionuclides are difficult to measure due to the fact that the measurements require both highly radioactive samples and intense neutron sources. Essential ingredients for describing the γ decays following neutron capture are the γ-ray strength function and level densities. We will compare different indirect approaches for obtaining the most relevant observables that can constrain Hauser-Feshbach statistical-model calculations of capture cross sections. Specifically, we will consider photon scattering using monoenergetic and 100% linearly polarized photonmore » beams. Here, challenges that exist on the path to obtaining neutron-capture cross sections for reactions on isotopes near and far from stability will be discussed.« less

Neutron Capture Reaction on 112Cd to Study of the s-process Origin of 115Sn

NASA Astrophysics Data System (ADS)

Hayakawa, Takehito; Toh, Yosuke; Shizuma, Toshiyuki; Kimura, Atsushi; Nakamura, Shoji; Harada, Hideo; Iwamoto, Nobuyuki; Kajino, Toshitaka; Chiba, Satoshi

The astrophysical origin of 115Sn has remained still an open question. An isomer with a half-life of 14.1 y in 113Cd is a branching point from which a nucleosynthesis flow reaches to a rare isotope 115Sn. The s-process abundance of 115Sn depends on the ratio of the 112Cd(n, γ)113Cdm reaction cross section to the 112Cd(n, γ)113Cdgs reaction cross section. However, the isomer production ratio following the neutron capture reaction has not been measured in an energy region higher than the thermal energy. We have measured γ-ray intensity ratios following neutron capture reactions on 112Cd using the HPGe detectors in conjunction with a time-of-flight method at ANNRI in J-PARC.

Applicability of the 2-nitroimidazole-sodium borocaptate-10B conjugate, TX-2060, as a 10B-carrier in boron neutron capture therapy.

PubMed

Masunaga, Shin-Ichiro; Nagasawa, Hideko; Hiraoka, Masamitsu; Sakurai, Yoshinori; Uto, Yoshihiro; Hori, Hitoshi; Nagata, Kenji; Suzuki, Minoru; Maruhashi, Akira; Kinashi, Yuko; Ono, Koji

2004-01-01

It is difficult to deliver a therapeutic amount of 10B from conventional 10B-carriers for boron neutron capture therapy (BNCT) throughout the target tumors, especially into the intratumor hypoxic cells which have low uptake capacities. We evaluated the usefulness of 5 new 10B-compounds (TX-2041, TX-2042, TX-2058, TX-2059 and TX-2060) as 10B-carriers in BNCT. They are 2-nitroimidazole-sodium borocaptate-10B (BSH) conjugates, that is, hybrid compounds that have both a hypoxic tumor cell sensitizing unit under gamma-ray irradiation, 2-nitroimidazoles and a thermal neutron-sensitizing unit, BSH. The 5 new compounds were administered to SCC VII tumor-bearing mice intraperitoneally. As a control, BSH was also administered in the same manner. Then, the 10B concentrations in the tumors and normal tissues were measured by gamma-ray spectrometry. Based on the data of the pharmacokinetics analyses, TX-2060 was chosen for a subsequent tumor-irradiation study. SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, then treated with TX-2060 or BSH in the same manner as in the pharmacokinetics analyses. To obtain similar intratumor 10B concentrations during radiation exposure, irradiation with thermal neutrons or gamma-rays was started from 60 min after administration of the 10B-carrier. Right after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU-labelling (= quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. The clonogenic cell survival was also determined in mice given no BrdU. 10B distribution analyses in tumors, muscles, blood and liver indicated that TX-2060 has the most

Commissioning optically stimulated luminescence in vivo dosimeters for fast neutron therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, Lori A., E-mail: layoung@uw.edu; Sandison, George; Yang, Fei

Purpose: Clinical in vivo dosimeters intended for use with photon and electron therapies have not been utilized for fast neutron therapy because they are highly susceptible to neutron damage. The objective of this work was to determine if a commercial optically stimulated luminescence (OSL) in vivo dosimetry system could be adapted for use in fast neutron therapy. Methods: A 50.5 MeV fast neutron beam generated by a clinical neutron therapy cyclotron was used to irradiate carbon doped aluminum oxide (Al{sub 2}O{sub 3}:C) optically simulated luminescence dosimeters (OSLDs) in a solid water phantom under standard calibration conditions, 150 cm SAD, 1.7more » cm depth, and 10.3 × 10.0 cm field size. OSLD fading and electron trap depletion studies were performed with the OSLDs irradiated with 20 and 50 cGy and monitored over a 24-h period to determine the optimal time for reading the dosimeters during calibration. Four OSLDs per group were calibrated over a clinical dose range of 0–150 cGy. Results: OSLD measurement uncertainties were lowered to within ±2%–3% of the expected dose by minimizing the effect of transient fading that occurs with neutron irradiation and maintaining individual calibration factors for each dosimeter. Dose dependent luminescence fading extended beyond the manufacturer’s recommended 10 min period for irradiation with photon or electron beams. To minimize OSL variances caused by inconsistent fading among dosimeters, the observed optimal time for reading the OSLDs postirradiation was between 30 and 90 min. No field size, wedge factor, or gantry angle dependencies were observed in the OSLDs irradiated by the studied fast neutron beam. Conclusions: Measurements demonstrated that uncertainties less than ±3% were attainable in OSLDs irradiated with fast neutrons under clinical conditions. Accuracy and precision comparable to clinical OSL measurements observed with photons can be achieved by maintaining individual OSLD calibration factors