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 a ^7Li（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 the ^7Li（p,n）^7Be reaction. Our designed beam has 2.49×109n/cm^2 s epithermal neutron flux and is suitable for BNCT of deep-seated brain tumors.     

基于蒙特卡罗方法的α粒子细胞S值计算

在放射性免疫治疗以及硼中子俘获治疗（BNCT）等放射性治疗过程中,粒子通过与人体组织材料相互作用产生次级电子将能量传递给人体组织,放射性核素在细胞尺度分布的不均匀性将严重影响靶区剂量分布。为深入了解放射性核素在细胞中不同位置分布对靶区剂量影响,采用基于历史凝聚算法的Monte Carlo 工具包Geant4编写了细胞S值计算程序。计算了2种细胞尺寸,12种粒子能量,3种源分布方式的细胞S值,与医学内照射剂量（MIRD）委员会解析算法的计算结果进行对比,发现两者差异在1%以内。证明了Geant4在m尺度下细胞剂量计算的可行性,并对BNCT治疗过程中产生的粒子(1.47 MeV与1.78 MeV)的细胞S值进行计算。     

Synthesis of a (B12H11S) containing glucuronoside as potential prodrug for BNCT

A B₁₂H₁₁SH²⁻ containing glycoside of glucuronic acid has been prepared, for possible use as prodrug in BNCT. The synthesis was carried out by the Koenigs-Knorr reaction of the acetylated glucopyranosyluronate bromide with the nucleophile cyanoethylthioundecahydro-closo-dodecaborate(2−). After removal of the cyanoethyl-group, deacetylation and saponification of the reaction product tris(tetramethylammonium)-[S-(β-d-glucuronate)-thio] undecahydro-closo-dodecaborate(3−) could be prepared.     

Two possible ways to combine boron and gadolinium for Gd-guided BNCT. A concept

Abstract

Two ways of synthesis of theragnostic compounds for Gd-guided boron neutron capture therapy of cancer are proposed. The first way is based on modification of DO3A ligand, which a capable to form stable complexes with gadolinium, with attachment of boron-containing moieties and additional functional groups which can be used for conjugation with various biomacromolecules. The second way is based on the introduction of additional chelating groups into a boron-containing moiety—carborane-based ligand. It is expected that this will significantly improve the stability of the gadolinium bis(dicarbollide) complexes.     

Synthesis of a Tyr-octreotate conjugated closo-carborane [HC2B10H10]: a potential compound for boron neutron capture therapy

A novel Tyr³-octreotate conjugated closo-carborane as a potential compound for boron neutron capture therapy was obtained via Fmoc solid phase peptide synthesis. The boron cluster [C₂B₁₀H₁₁] was introduced through the reaction of 6,9-bis(acetonitrile)decaborane and 5-hexynoic acid yielding a new closo-carborane conjugated carboxylic acid which was coupled subsequently with solid phase conjugated Tyr³-octreotate. The final boron-containing peptide was purified by preparative reverse phase HPLC and structural identity was proved applying MALDI-TOF mass spectrometry.     

Crystallographic report: Synthesis and biological evaluation of novel azanonaboranes as potential agents for boron neutron capture therapy

A number of (hydroxyalkylamine)‐N‐(aminoalkyl)azanonaborane(11) derivatives have been synthesized to provide azanonaboranes with different hydrophilic functional groups for use in the treatment of cancer by boron neutron capture therapy (BNCT). The exo‐diamine group of (aminoalkylamine)‐N‐(aminoalkyl)azanonaborane(11) {H₂N(CH₂)_mH₂NB₈H₁₁NH(CH₂)_mNH₂, where m = 4–6} can be substituted by amino alcohol ligands {HO(CH₂)_nNH₂, where n = 3 and 4} to give azanonaboranes containing free amino and hydroxy groups: (3‐hydroxypropylamine)‐N‐(aminobutyl)azanonaborane(11) {HO(CH₂)₃H₂NB₈H₁₁NH(CH₂)₄NH₂}, 1 ; (4‐hydroxybutylamine)‐N‐ (aminobutyl)azanonaborane(11) {HO(CH₂)₄H₂NB₈H₁₁NH(CH₂)₄NH₂}, 2 ; (3‐hydroxypropylamine)‐N‐ (aminopentyl)azanonaborane(11) {HO(CH₂)₃H₂NB₈H₁₁NH(CH₂)₅NH₂}, 3 ; (4‐hydroxypropylamine)‐N‐(aminopentyl)azanonaborane(11) {HO(CH₂)₄H₂NB₈H₁₁NH(CH₂)₅NH₂}, 4 ; (3‐hydroxypropylamine)‐N‐(aminohexyl)azanonaborane(11) {HO(CH₂)₃H₂NB₈H₁₁NH(CH₂)₆NH₂}, 5 . The in vitro toxicity test using Chinese hamster‐V79 cells showed that compounds 1 – 3 were less toxic (LD₅₀ value of ～2.3, 1.7 and 1.4 mM , respectively) than spermine and spermidine (LD₅₀ value of ～0.88 and 0.66 mM , respectively). In vivo distribution experiments of these compounds in Lewis lung carcinoma and B16 melanoma tumor‐bearing mice showed that boron can be found in tumor tissue. The compounds prepared can be considered as a new class of boron containing polyamine compounds that may be useful for boron neutron capture therapy of tumors. Copyright © 2005 John Wiley & Sons, Ltd.     

Measurement of B concentration through autoradiography images in polycarbonate nuclear track detectors

The determination of the local concentration of boron in the different regions of tissue samples treated by Boron Neutron Capture Therapy (BNCT) could be made through the evaluation of the number of tracks forming autoradiography images. It is necessary to get a “standard” material containing a known amount of ¹⁰B, to correlate the number of tracks and boron concentration, i.e. to be used as a reference.Different systems were tested in order to find a suitable standard. Films made of 2% agarose in boron solutions showed a homogeneous distribution of the ¹⁰B atoms in the material structure. This system is easy handled and its physical properties are satisfactory.On the other hand, a small volume polycarbonate box was designed to contain ¹⁰B solutions of known concentration. This system showed a reduced number of background tracks and a promising behavior in many aspects. There is proportionality between track numbers per surface unit and ¹⁰B concentration, and between track numbers per surface unit and neutron fluence. Experimental results were compared to calculated values through formulas developed for thick samples autoradiography.     

Novel types of carborane-carrier hyaluronan derivatives via "click chemistry"

Two new HA derivatives bearing carborane rings were synthesized by click chemistry. The optimal conditions were assessed for the preparation of biocompatible boron carriers, potentially suitable for application in BNCT and capable of targeting the CD44 antigen. The new polymeric samples were characterized by means of NMR-spectroscopy techniques that gave degrees of 17 and 8% for HAAACB and HapACB, respectively. Both HAAACB and HApACB turned out to be nontoxic for colorectal, ovarian and bladder tumor cell lines, to disclose a specific interaction with the CD44 antigen as the native hyaluronan moiety, and to deliver boron-atom concentrations largely sufficient for BNCT therapy when accumulated in cancer cells.     

BNCT治疗规划系统MCDB算法及测试

给出BNCT治疗计划系统软件MCDB的算法及测试结果,通过使用材料矩阵描述BNCT的网格模型,配合快速径迹算法和计数矩阵,进行粒子输运模拟及计数,模拟结果显示,MCDB的计算精度与MCNP相当,计算速度较MCNP提高3.1~3.4倍.MCDB模拟1 000万粒子的时间不足2个CPU小时,可保证大部分网格剂量误差在5%以内,基本上达到了BNCT临床要求,可用于30 kW的医院中子照射器的临床治疗.     

Novel carboranylporphyrins for application in boron neutron capture therapy (BNCT) of tumors

Condensation of a new carboranylpyrrole 1 with benzaldehydes leads to β-carboranylporphyrins 2 and 3 in good yields. These new porphyrins of high boron content (32-43%) have potential as boron delivery agents for BNCT. The X-ray structures of one β-carboranylporphyrin, of a carboranylpyrrole, and of a side-product are presented.