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Boron neutron capture therapy

Diego Alberti, Annamaria Deagostino, Antonio Toppino, Nicoletta Protti, Silva Bortolussi, Saverio Altieri, Silvio Aime, Simonetta Geninatti Crich
The aim of this study is to develop an innovative imaging guided approach based on Boron Neutron Capture Therapy, for the treatment of mesothelioma, assisted by the quantification of the in vivo boron distribution by MRI. The herein reported results demonstrate that overexpressed Low Density Lipoproteins receptors can be successfully exploited to deliver to mesothelioma cells a therapeutic dose of boron (26 μg/g), significantly higher than in the surrounding tissue (3.5 μg/g). Boron and Gd cells uptake was assessed by ICP-MS and MRI on two mesothelioma (ZL34, AE17) and two healthy (MRC-5 and NMuMg) cell lines...
May 3, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Shingo Harada, Ryota Kajihara, Risa Muramoto, Promsuk Jutabha, Naohiko Anzai, Tetsuhiro Nemoto
p-Boronophenylalanine (l-BPA) is applied in clinical settings as a boron carrier for boron neutron capture therapy (BNCT) to cure malignant melanomas. Structural modification or derivatization of l-BPA, however, to improve its uptake efficiency into tumor cells has scarcely been investigated. We successfully synthesized (S)-2-amino-3-(4-boronophenyl)-2-methylpropanoic acid in enantioenriched form as a novel candidate molecule for BNCT. Key steps to enhance the efficiency of this synthesis were enantioselective alkylation of N-protected alanine tert-butyl ester with a Maruoka catalyst and Miyaura borylation reaction to install the boron functionality...
March 28, 2018: Bioorganic & Medicinal Chemistry Letters
Lucas Provenzano, María Silvina Olivera, Gisela Saint Martin, Luis Miguel Rodríguez, Daniel Fregenal, Silvia I Thorp, Emiliano C C Pozzi, Paula Curotto, Ian Postuma, Saverio Altieri, Sara J González, Silva Bortolussi, Agustina Portu
The neutron autoradiography technique using polycarbonate nuclear track detectors (NTD) has been extended to quantify the boron concentration in hard tissues, an application of special interest in Boron Neutron Capture Therapy (BNCT). Chemical and mechanical processing methods to prepare thin tissue sections as required by this technique have been explored. Four different decalcification methods governed by slow and fast kinetics were tested in boron-loaded bones. Due to the significant loss of the boron content, this technique was discarded...
March 14, 2018: Applied Radiation and Isotopes
Mitsuyoshi Yoshimoto, Natsuki Honda, Hiroaki Kurihara, Kenta Hiroi, Satoshi Nakamura, Masashi Ito, Naoto Shikano, Jun Itami, Hirofumi Fujii
In boron neutron capture therapy (BNCT), 10 B-4-borono-L-phenylalanine (BPA) is commonly used as a 10 B carrier. PET using 4-borono-2-18 F-fluoro-phenylalanine (18 F-FBPA PET) has been performed to estimate boron concentration and predict the therapeutic effects of BNCT; however, the association between tumor uptake of 18 F-FBPA and boron concentration in tumors remains unclear. The present study investigated the transport mechanism of 18 F-FBPA and BPA, and evaluated the utility of 18 F-FBPA PET in predicting boron concentration in tumors...
March 2, 2018: Cancer Science
Natalia M Espector, Agustina Portu, Gustavo A Santa Cruz, Gisela Saint Martin
The analysis of the distribution and density of nuclear tracks forming an autoradiography in a nuclear track detector (NTD) allows the determination of 10 B atoms concentration and location in tissue samples from Boron Neutron Capture Therapy (BNCT) protocols. This knowledge is of great importance for BNCT dosimetry and treatment planning. Tissue sections studied with this technique are obtained by cryosectioning frozen tissue specimens. After the slicing procedure, the tissue section is put on the NTD and the sample starts drying...
May 2018: Radiation and Environmental Biophysics
C Rodriguez, M Carpano, P Curotto, S Thorp, M Casal, G Juvenal, M Pisarev, M A Dagrosa
Boron neutron capture therapy (BNCT) for aggressive tumors is based on nuclear reaction [10 B (n, α) 7 Li]. Previously, we demonstrated that BNCT could be applied for the treatment of undifferentiated thyroid carcinoma. The aim of the present study was to describe the DNA damage pattern and the repair pathways that are activated by BNCT in thyroid cells. We analyzed γH2AX foci and the expression of Ku70, Rad51 and Rad54, main effector enzymes of non-homologous end joining (NHEJ) and homologous recombination repair (HRR) pathways, respectively, in thyroid follicular carcinoma cells...
May 2018: Radiation and Environmental Biophysics
Leyla Moghaddasi, Eva Bezak
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...
March 2018: Australasian Physical & Engineering Sciences in Medicine
G A P Cirrone, L Manti, D Margarone, G Petringa, L Giuffrida, A Minopoli, A Picciotto, G Russo, F Cammarata, P Pisciotta, F M Perozziello, F Romano, V Marchese, G Milluzzo, V Scuderi, G Cuttone, G Korn
Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12 C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12 C-ion clinical amenability...
January 18, 2018: Scientific Reports
Bo-Lun Lai, Rong-Jiun Sheu
Material activation assessment of a proposed accelerator-based boron neutron capture therapy facility was performed using the FLUKA Monte Carlo code to quantify the magnitude of the problem in terms of the isotope inventories, induced activities, and residual dose rates. Two simplified operation scenarios were considered: a 30-min proton bombardment to simulate a typical session of patient treatment and a long-term 1 year continuous operation to estimate the accumulation of long-lived radionuclides. Following the generation and transport of decay radiation, the space- and time-dependent inventories of induced radionuclides in materials and residual dose rates after shutdown were obtained...
January 16, 2018: Radiation Protection Dosimetry
Tatsuhiko Sato, Shin-Ichiro Masunaga, Hiroaki Kumada, Nobuyuki Hamada
We here propose a new model for estimating the biological effectiveness for boron neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity in 10B 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...
January 17, 2018: Scientific Reports
Takahiro Morita, Hiroaki Kurihara, Kenta Hiroi, Natsuki Honda, Hiroshi Igaki, Jun Hatazawa, Yasuaki Arai, Jun Itami
BACKGROUND: We evaluated dynamic changes in 18 F-borono-L-phenylalanine (18 F-BPA) uptake in unresectable, advanced, or recurrent squamous cell carcinoma of the head and neck (SCC) and malignant melanoma (MM) during boron neutron capture therapy (BNCT) patient selection. METHODS: Dynamic changes in the maximum standardized uptake value (SUVmax), tumor-to-normal tissue ratio (TNR), and tumor-to-blood pool ratio (TBR) for 18 F-BPA were evaluated in 20 patients with SCC and 8 patients with MM...
January 11, 2018: Radiation Oncology
Yuki Wada, Katsumi Hirose, Takaomi Harada, Mariko Sato, Tsubasa Watanabe, Akira Anbai, Manabu Hashimoto, Yoshihiro Takai
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...
March 1, 2018: Journal of Radiation Research
Eisuke Sato, Alexander Zaboronok, Tetsuya Yamamoto, Kei Nakai, Sergey Taskaev, Olga Volkova, Ludmila Mechetina, Alexander Taranin, Vladimir Kanygin, Tomonori Isobe, Bryan J Mathis, Akira Matsumura
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...
March 1, 2018: Journal of Radiation Research
Satoshi Nakamura, Shoji Imamichi, Kazuyoshi Masumoto, Masashi Ito, Akihisa Wakita, Hiroyuki Okamoto, Shie Nishioka, Kotaro Iijima, Kazuma Kobayashi, Yoshihisa Abe, Hiroshi Igaki, Kazuyoshi Kurita, Teiji Nishio, Mitsuko Masutani, Jun Itami
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, and42 K were identified, and their saturated radioactivities were (1...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Ayse Karaoglu, Pedro Arce, Diego Obradors, Juan I Lagares, Perihan Unak
Monte Carlo (MC) has demonstrated to be a suitable technique to evaluate the microdosimetric parameters at the cellular level for Boron Neutron Capture Therapy (BNCT). The objectives of the current study are first to validate GAMOS MC codes with different Geant4 physics models for the range calculations of alpha particles. Once the proper physics is selected, the second objective is to determine the distributions of deposited energy in cellular medium originated by alpha and lithium-7 particles induced by10 B(n,α)7 Li...
February 2018: Applied Radiation and Isotopes
Arthur B Volovetsky, Vladimir S Sukhov, Irina V Balalaeva, Varvara V Dudenkova, Natalia Yu Shilyagina, Аlexey V Feofanov, Anastasija V Efremenko, Mikhail A Grin, Andrey F Mironov, Igor B Sivaev, Vladimir I Bregadze, Anna V Maslennikova
The necessary precondition for efficient boron neutron capture therapy (BNCT) is control over the content of isotope10 B in the tumor and normal tissues. In the case of boron-containing porphyrins, the fluorescent part of molecule can be used for quantitative assessment of the boron content. Study Objective: We performed a study of the biodistribution of the chlorin e ₆-Cobalt bis(dicarbollide) conjugate in carcinoma-bearing Balb/c mice using ex vivo fluorescence imaging, and developed a mathematical model describing boron accumulation and release based on the obtained experimental data...
November 28, 2017: International Journal of Molecular Sciences
Ryoichi Seki, Yushi Wakisaka, Nami Morimoto, Masaaki Takashina, Masahiko Koizumi, Hiroshi Toki, Mitsuhiro Fukuda
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.
December 2017: Radiological Physics and Technology
Yangjian Quan, Zaozao Qiu, Zuowei Xie
Carboranes are a class of carbon-boron molecular clusters with unusual thermal and chemical stabilities. They have been proved as very useful building blocks in supramolecular design, optoelectronics, nanomaterials, boron neutron capture therapy agents and organometallic/coordination chemistry. Thus, the functionalization of o-carboranes has received growing interests. Over the past decades, most of the works in this area have been focused on cage carbon functionalization as the weakly acidic cage C-H proton can be readily deprotonated by strong bases...
February 26, 2018: Chemistry: a European Journal
Wellington Marcos da Silva, Tiago Hilário Ferreira, Carlos Antônio de Morais, Alexandre Soares Leal, Edésia Martins Barros Sousa
Boron nitride nanotubes doped in situ with samarium (Sm-doped BNNTs) were synthesized at 1150°C under atmosphere of NH3 /N2 gas mixture by thermal chemical vapor deposition (TCVD) using samarium oxide that is a product of the process separation of thorium and uranium tailings. The samarium in the BNNTs sample was activated by neutron capture, in a nuclear reactor, producing152 Sm radioisotopes. The STEM-EELS spectrum and neutron activation show energies attributed to the samarium confirming the in situ doping process during BNNTs growth...
January 2018: Applied Radiation and Isotopes
Yu-Chi Bai, Yu-Chun Hsia, Yu-Ting Lin, Kuan-Hao Chen, Fong-In Chou, Chia-Min Yang, Yung-Jen Chuang
BACKGROUND: Feasibility and efficacy of boric acid (BA)-mediated boron neutron capture therapy (BNCT) was first demonstrated by eliminating hepatocellular carcinoma (HCC) in a rat model. Furthermore, selective uptake of BA by liver tumor cells was shown in a rabbit model. To gain further insight, this study aimed to investigate the mechanisms of transportation and selective uptake of BA in HepG2 liver tumor cells. MATERIALS AND METHODS: Transportation of BA in HepG2 cells was analyzed by time-course assays and by analyzing the rate of diffusion versus the concentration of BA...
November 2017: Anticancer Research
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