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Boron neutron capture therapy

Łukasz Uram, Joanna Nizioł, Piotr Maj, Justyna Sobich, Wojciech Rode, Tomasz Ruman
Glioblastoma multiforme (GBM) is a central nervous system tumor of grade IV, according to the WHO classification, extremely resistant to all currently used forms of therapy, including resection, radiotherapy, chemotherapy or combined therapy. Therefore, more effective treatment strategies of this tumor are needed, with boron neutron capture therapy (BNCT) being a potential solution, provided a proper cancer cells-targeted 10B delivery agent is found. In search of such an agent, toxicity and capacity to target DNA of a boronated derivative of 2'-deoxycytidine, N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2'-deoxycytidine (1), was tested against human tumor vs...
September 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Gianpiero Calabrese, Anis Daou, Eugen Barbu, John Tsibouklis
Boron neutron capture therapy (BNCT) is a promising targeted chemoradiotherapeutic technique for the management of invasive brain tumors, such as glioblastoma multiforme (GBM). A prerequisite for effective BNCT is the selective targeting of tumour cells with (10)B-rich therapeutic moieties. To this end, polyhedral boranes, especially carboranes, have received considerable attention because they combine a high boron content with relative low toxicity and metabolic inertness. Here, we review progress in the molecular design of recently investigated carborane derivatives in light of the widely accepted performance requirements for effective BNCT...
September 5, 2017: Drug Discovery Today
Andrea Monti Hughes, Juan Longhino, Esteban Boggio, Vanina A Medina, Diego J Martinel Lamas, Marcela A Garabalino, Elisa M Heber, Emiliano C C Pozzi, María E Itoiz, Romina F Aromando, David W Nigg, Verónica A Trivillin, Amanda E Schwint
Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new "B2" configuration...
September 4, 2017: Radiation and Environmental Biophysics
Abdollah Khorshidi
AIMS: 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. MATERIALS AND METHODS: An epithermal neutron spectrum generator was simulated with 30 MeV proton energy for BNCT purposes...
July 2017: Journal of Cancer Research and Therapeutics
Sara Josefina Gonzalez, Emiliano C C Pozzi, Andrea Monti Hughes, Lucas Provenzano, Hanna Koivunoro, Daniel Germán Carando, Silvia Inés Thorp, Mariana Rosalía Casal, Silva Bortolussi, Verónica A Trivillin, Marcela A Garabalino, Paula Curotto, Elisa M Heber, Gustavo A Santa Cruz, Leena Kankaanranta, Heikki Joensuu, Amanda E Schwint
Boron Neutron Capture Therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans...
August 31, 2017: Physics in Medicine and Biology
Tomasz M Goszczyński, Krzysztof Fink, Konrad Kowalski, Zbigniew J Leśnikowski, Janusz Boratyński
Boron clusters are polyhedral boron hydrides with unique properties, and they are becoming increasingly widely used in biology and medicine, including for boron neutron capture therapy (BNCT) of cancers and in the design of novel bioactive molecules and potential drugs. Among boron cluster types, icosahedral boranes, carboranes, and metallacarboranes are particularly interesting, and there is a need for basic studies on their interaction with biologically important molecules, such as proteins. Herein, we report studies on the interaction of selected boron clusters and their derivatives with serum albumin, the most abundant protein in mammalian blood...
August 29, 2017: Scientific Reports
Damian Kaniowski, Katarzyna Ebenryter-Olbińska, Milena Sobczak, Błażej Wojtczak, Sławomir Janczak, Zbigniew J Leśnikowski, Barbara Nawrot
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...
August 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Silva Bortolussi, Ian Postuma, Nicoletta Protti, Lucas Provenzano, Cinzia Ferrari, Laura Cansolino, Paolo Dionigi, Olimpio Galasso, Giorgio Gasparini, Saverio Altieri, Shin-Ichi Miyatake, Sara J González
BACKGROUND: 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...
August 15, 2017: Radiation Oncology
Issei Takeuchi, Kensuke Nomura, Kimiko Makino
Poly(DL-lactide-co-glycolide) (PLGA) has been widely used and studied because of its biocompatibility and biodegradability. Recently, the usefulness of nanoparticles using poly(L-lactide-co-glycolide) (PLLGA) having a higher glass transition temperature than PLGA was suggested. In this study, we investigated the availability of boron compound-loaded PLGA and PLLGA nanoparticles for boron neutron capture therapy (BNCT) by conducting biodistribution study using tumor-bearing mice. o-Carborane, a hydrophobic boron compound, was used as a boron carrier, and o-carborane-albumin conjugate was used as a control...
August 4, 2017: Colloids and Surfaces. B, Biointerfaces
Verónica A Trivillin, Emiliano C C Pozzi, Lucas L Colombo, Silvia I Thorp, Marcela A Garabalino, Andrea Monti Hughes, Sara J González, Rubén O Farías, Paula Curotto, Gustavo A Santa Cruz, Daniel G Carando, Amanda E Schwint
The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10(6) DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue...
August 8, 2017: Radiation and Environmental Biophysics
Leyla Moghaddasi, Eva Bezak
Glioblastomas (GBM) are notorious for their high fatality rate. Boron Neutron Capture Therapy (BNCT) being a biochemically targeted type of radiotherapy is a potent modality for GBM. In the current work, a BNCT treatment modelling framework for GBM was developed. Optimal Clinical Target Volume (CTV) margins for GBM-BNCT and the BNCT efficacy have been investigated. The model integrated a cell-based dosimetry model, an in-house-developed epithermal neutron beam model and previously-developed Microscopic Extension Probability (MEP) model...
August 1, 2017: Scientific Reports
Chun-Nan Yeh, Chi-Wei Chang, Yi-Hsiu Chung, Shi-Wei Tien, Yong-Ren Chen, Tsung-Wen Chen, Ying-Cheng Huang, Hsin-Ell Wang, You-Cheng Chou, Ming-Huang Chen, Kun-Chun Chiang, Wen-Sheng Huang, Chung-Shan Yu
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)...
July 17, 2017: European Journal of Pharmaceutical Sciences
Charles A Maitz, Aslam A Khan, Peter J Kueffer, John D Brockman, Jonathan Dixson, Satish S Jalisatgi, David W Nigg, Thomas A Everett, M Frederick Hawthorne
Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. Mice were implanted with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the lipid bilayer and encapsulated Na3[1-(2`-B10H9)-2-NH3B10H8] within the liposomal core...
August 2017: Translational Oncology
Kenichi Tanaka, Yoshinori Sakurai, Shin-Ichiro Hayashi, Tsuyoshi Kajimoto, Ryohei Uchida, Hiroki Tanaka, Takushi Takata, Gerard Bengua, Satoru Endo
This study investigated the optimum composition of the MAGAT polymer gel which is to be used in the quality assurance measurement of the thermal neutron, fast neutron and gamma ray components in the irradiation field used for boron neutron capture therapy at the Kyoto University Reactor. Simulations using the PHITS code showed that when combined with the gel, (6)Li concentrations of 0, 10 and 100ppm were found to be potentially usable.
June 15, 2017: Applied Radiation and Isotopes
Jia-Cheng Lee, Keh-Shih Chuang, Yi-Wei Chen, Fang-Yuh Hsu, Fong-In Chou, Sang-Hue Yen, Yuan-Hung Wu
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...
2017: PloS One
Satoru Endo, Hitoshi Sato, Takuto Shimazaki, Erika Nakajima, Kei Kotani, Mitsuru Suda, Tsuyoshi Hamano, Tsuyoshi Kajimoto, Kenichi Tanaka, Masaharu Hoshi
An LBO (Li2B4O7) walled ionization chamber was designed to monitor the epithermal neutron fluence in boron neutron capture therapy clinical irradiation. The thermal and epithermal neutron sensitivities of the device were evaluated using accelerator neutrons from the (9)Be(d, n) reaction at a deuteron energy of 4 MeV (4 MeV d-Be neutrons). The response of the chamber in terms of the electric charge induced in the LBO chamber was compared with the thermal and epithermal neutron fluences measured using the gold-foil activation method...
August 2017: Radiation and Environmental Biophysics
Naresh Kuthala, Raviraj Vankayala, Yi-Nan Li, Chi-Shiun Chiang, Kuo Chu Hwang
Glioblastoma multiforme (GBM) is a very common type of "incurable" malignant brain tumor. Although many treatment options are currently available, most of them eventually fail due to its recurrence. Boron neutron capture therapy (BNCT) emerges as an alternative noninvasive therapeutic treatment modality. The major challenge in treating GBMs using BNCT is to achieve selective imaging, targeting, and sufficient accumulation of boron-containing drug at the tumor site so that effective destruction of tumor cells can be achieved without harming the normal brain cells...
June 16, 2017: Advanced Materials
H Tanaka, Y Sakurai, T Takata, T Watanabe, S Kawabata, M Suzuki, S-I Masunaga, K Taki, K Akabori, K Watanabe, K Ono
The real-time detection of epithermal neutrons forms an important aspect of boron neutron capture therapy. In this context, we developed an epithermal neutron detector based on the combination of a small Eu:LiCaAlF6 scintillator and a quartz fiber in order to fulfill the irradiation-field requirements for boron neutron capture therapy. The irradiation test is performed with the use of a reactor-based neutron source. The thermal and epithermal neutron sensitivities of our epithermal neutron detector are estimated to be 9...
May 2017: Review of Scientific Instruments
Natsuko Kondo, Rolf F Barth, Shin-Ichi Miyatake, Shinji Kawabata, Minoru Suzuki, Koji Ono, Norman L Lehman
We have used boron neutron capture therapy (BNCT) to treat patients in Japan with newly diagnosed or recurrent high-grade gliomas and have observed a significant increase in median survival time following BNCT. Although cerebrospinal fluid dissemination (CSFD) is not usually seen with the current standard therapy of patients with glioblastoma (GBM), here we report that subarachnoid or intraventricular CSFD was the most frequent cause of death for a cohort of our patients with high-grade gliomas who had been treated with BNCT...
May 22, 2017: Journal of Neuro-oncology
Akihiko Masuda, Tetsuro Matsumoto, Kenta Takada, Takahiro Onishi, Kohei Kotaki, Hidenori Sugimoto, Hiroaki Kumada, Hideki Harano, Takeji Sakae
The neutron spectral fluence of an accelerator-based neutron source facility for boron neutron capture therapy (BNCT) based on a proton linac and a beryllium target was evaluated by the unfolding method using a Bonner sphere spectrometer (BSS). A (3)He-proportional-counter-based BSS was used with weak beam during the development of the facility. The measured epithermal neutron spectra were consistent with calculations. The epithermal neutron intensity at the beam port was estimated and the results gave a numerical target for the enhancement of the proton beam intensity and will be used as reference data for measurements performed after the completion of the facility...
May 10, 2017: Applied Radiation and Isotopes
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