Kohonen classification applying ‘missing variables’ criterion to evaluate the p‐boronophenylalanine human‐body‐concentration decreasing profile of boron neutron capture therapy patients

The irradiation dose in tumor and healthy tissue of a boron neutron capture therapy (BNCT) patient depends on the boron concentration in blood. In most treatments, this concentration is experimentally determined before and after irradiation but not while irradiation is being carried out because it is troublesome to take the blood samples when the patient remains isolated in the irradiation room. A few models are used to predict the boron profile during that period, which until now involves a biexponential decay. For the prediction of decay concentration profiles of the p‐boronophenylalanine (BPA) in the human body during BNCT treatment, a Kohonen‐based neural network method is suggested. The results of various (20 × 20 × 40 Kohonen network) models based on different trainings on the data set of 67 concentration sets (profiles) are described and discussed. The prediction ability and robustness of the modeling method were tested by the leave‐one‐out procedure. The results show that the method is very robust and mostly independent of small variations. It can yield predictions, root mean squared prediction error (RMSPE), with a maximum of 3.30 µg g⁻¹ for the present cases. In order to show the abilities and limitations of the method, the best and the few worst results are discussed in detail. It should be emphasized that one of the main advantages of this method is the automatic improvement in the prediction ability and robustness of the model by feeding it with an increasing number of data. Copyright © 2011 John Wiley & Sons, Ltd.     

Conjugates of polyhedral boron compounds with carbohydrates. 4. hydrolytic stability of carborane–lactose conjugates depends on the structure of a spacer between the carborane cage and sugar moiety

A novel 1,2‐dicarba‐closo‐dodecaborane–lactose conjugate ( 4a ) with an N‐glycosidic linkage was synthesized. This conjugate was found to be much more stable against hydrolytic deboronation (closo to nido tranformation of the carborane cage) under neutral conditions than a related carborane–lactose conjugate ( 1a ) with an O‐glycosidic linkage. This result demonstrates that the hydrolytic stability of carborane–carbohydrate conjugates in neutral aqueous solutions may depend dramatically on the chemical nature of the spacer that links the carbohydrate moiety with the boron cage, the rate of hydrolysis varying by orders of magnitude. We relate a significant decrease in the deboronation rate to the formation of more strongly bound supramolecular aggregates, in which the boron cage is less accessible to nucleophilic attack by solvent molecules, in the solution of the carborane–N‐lactoside conjugate 4a . Copyright © 2006 John Wiley & Sons, Ltd.     

Nano and dendritic structured carboranes and metallacarboranes: From materials to cancer therapy

An account of the current research carried out in our laboratories is presented. Included is the incorporation of several group 14 elements into charge-compensated carboranes. These species present a bonding pattern not found in other main group carboranes. In addition to our continuing studies of the syntheses and structures of organometallic compounds, the use of these compounds as catalysts and catalyst precursors has been investigated. The isotopic exchange reactions between ¹⁰B enriched boron hydrides with naturally abundant boranes catalyzed by Ru(0) nanoparticles has been studied. The Ru(0) nanoparticles were obtained by the reduction of [CpRuCp^∗RuCp^∗]PF₆ (Cp^∗ = C₅Me₅) with hydrogen and stabilized by the ionic liquid trihexyltetradecylphosphonium dodecylbenzenesulfonate [THTdP][DBS]. This was found to be an excellent, long lived catalyst for the exchange reaction of B-10 enriched diborane and naturally abundant decaborane(14). Other approaches to the production and use of nano-metal catalysts have also been explored. The reduction of the iridium carborane, (PPh₃)₂IrH(7,8-C₂B₉H₁₁) with hydrogen in the presence of trihexyltetradecylphosphonium methylsulfonate, [THTdP][MS], produced an Ir(0) nanoparticles that catalyzed the phenylborolation as did our Ir(sal = N-R = salicylaldiminato; COD = cyclooctadiene complex. Progress in the use of single wall carbon nanotubes (SWCNT) as boron delivery agents was also discussed.     

Measurement of dose enhancement by neutron capture of boron in Cf interstitial brachytherapy

The effect of boron concentration in water on the gamma, fast and slow neutrons and alpha particles components at the central, forward and backward surfaces inside tumor phantom of 4.2 cm diameter and 4.4cm height, during brachytherapy by neutrons from ²⁵²Cf were investigated. The source was at the centre of a cubic shaped water phantom of 30 cm side. The study was carried for different concentrations of boron from H₃BO₃, Li₂B₄O₇ and H₃¹⁰BO₃. The effect of source to tumor distance on the different components of radiation was also measured. The results indicated that the use of ¹⁰B compounds enhances the damage and is recommended for successful boron neutron capture therapy (BNCT).     

Intercomparative studies of brachytherapy techniques combined with CF Boron neutron capture therapy

In this work the depth dose distribution for γ-rays, slow and fast neutrons, nuclear recoils and -particles inside a tumor phantom filled with 100 ppm ¹⁰B in distilled water was measured. The depth dose distributions were measured and represented on three-dimensional plots when a ²⁵²Cf neutron source was situated in interstitial, surface and intracavitary brachytherapy techniques. Comparison of the three brachytherapy techniques when combined with BNCT revealed that the damage induced in the tumor by the -particles as nuclear recoils in the interstitial geometry is much more than the other two techniques.     

Neutron beam optimization based on a ~7Li(p,n)~7Be reaction for treatment of deep-seated brain tumors by BNCT

Neutron beam optimization for accelerator-based Boron Neutron Capture Therapy(BNCT) is investigated using a7Li(p,n)7Be reaction. Design and optimization have been carried out for the target, cooling system,moderator, filter, reflector, and collimator to achieve a high flux of epithermal neutron and satisfy the IAEA criteria.Also, the performance of the designed beam in tissue is assessed by using a simulated Snyder head phantom. The results show that the optimization of the collimator and reflector is critical to finding the best neutron beam based on the7Li(p,n)7Be reaction. Our designed beam has 2.49×109n/cm2 s epithermal neutron flux and is suitable for BNCT of deep-seated brain tumors.     

10B-editing 1H-detection and 19F MRI strategies to optimize boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a binary radiation therapy used to treat malignant brain tumours. It is based on the nuclear reaction (10B + n th --> [11B*] --> alpha + 7Li + 2.79 MeV) that occurs when 10B captures a thermal neutron to yield alpha particles and recoiling 7Li nuclei, both responsible of tumour cells destruction by short range and high ionization energy release. The clinical success of the therapy depends on the selective accumulation of the 10B carriers in the tumour and on the high thermal neutron capture cross-section of 10B. Magnetic resonance imaging (MRI) methods provide the possibility of monitoring, through 10B nuclei, the metabolic and physiological processes suitable to optimize the BNCT procedure. In this study, spatial distribution mapping of borocaptate (BSH) and 4-borono-phenylalanine (BPA), the two boron carriers used in clinical trials, has been obtained. The BSH map in excised rat brain and the 19F-BPA image in vivo rat brain, representative of BPA spatial distribution, were reported. The BSH image was obtained by means of double-resonance 10B-editing 1H-detection sequence, named M-Bend, exploiting the J-coupling interaction between 10B and 1H nuclei. Conversely, the BPA map was obtained by 19F-BPA using 19F-MRI. Both images were obtained at 7 T, in C6 glioma-bearing rat brain. Our results demonstrate the powerful of non conventional MRI techniques to optimize the BNCT procedure.     

Synthesis, aggregation and cellular investigations of porphyrin-cobaltacarborane conjugates

A new series of porphyrin-cobaltacarborane conjugates (1-5) that contain four to sixteen carborane clusters per porphyrin macrocycle, were prepared in excellent yields (90-97 %) by means of a ring-opening reaction of the zwitterionic cobaltacarborane [3,3'-Co(8-C(4)H(8)O(2-)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))]. The X-ray structure of one conjugate (3) is presented. The aggregation properties of these conjugates were investigated by using absorption and fluorescence spectrophotometry, and the stages of microcrystal formation were captured by using atomic force microscopy. All conjugates were found to aggregate in aqueous solutions, to form a broad dispersity of particle sizes. The cellular uptake, cytotoxicity, and preferential sites of subcellular localization of this series of conjugates were evaluated in human carcinoma HEp2 cells. The extent of conjugate cellular uptake depends on the number of cobaltacarborane units at the porphyrin periphery, their distribution, and the conjugate aggregation behavior. Conjugates 2 and 4, bearing either two adjacent or three 3,5-dicobaltacarboranephenyl groups, accumulated the most within HEp2 cells and are, therefore, the most promising boron neutron capture therapy agents. All conjugates showed very low dark- and photo-toxicity, probably due to their strong tendency for aggregation in aqueous solutions, and localized subcellularly within vesicles that correlated, to some extent, with the cell lysosomes.     

BNCT蒙特卡罗剂量计算中网格构造和材料确定的一种简便方法

BNCT国际基准问题分别推出了16 mm,8 mm和4 mm三种标准化网格模型,用MCNP蒙特卡罗程序模拟了这些模型,并与Snyder解析模型进行了比较.在此基础上,给出了一种质量守恒好,网格逼近程度高,且基于4种基本材料成份的BNCT网格构造方法.计算结果表明,在4 mm网格尺寸上,新方法采用基本材料模型可以达到采用混合材料模型的精度;用这种方法进一步产生了5 mm网格模型,把模拟结果和解析模型进行了比较,发现5 mm网格模型大脑内剂量计算误差较小,质量守恒好,并且能大大节省计算机模拟的时间,是一种很好的优化网格.     

Synthesis of adenosine containing carborane modification

The carboranyl cage is a new modifying entity for nucleosides and DNA-oligonucleotides. Most of carborane–nucleoside conjugates described so far belong to pyrimidine series. Herein, the first synthesis of adenosine, nucleoside containing purine nucleic base, modified with carborane cluster, is described.