硼对大鼠肠道氟吸收影响的研究

16只Wistar大鼠随机分成对照组和实验组,应用原位肠道灌流技术给对照组灌流氟化水,实验组灌流氟硼混合水,观察硼对大鼠肠道氟吸收的影响。结果表明,两组动物均可经肠道吸收大量氟离子;实验组肠道内有BF_4~-络合物的形成;与灌流前比较,两组动物血氟均显著升高,但实验组血氟增加程度明显低于对照组。提示:BF_4~-络合物的形成可减少肠道的氟吸收量,使血氟浓度降低。     

Common challenges and problems in clinical trials of boron neutron capture therapy of brain tumors

Summary Clinical trials for binary therapies, like boron neutron capture therapy (BNCT), pose a number of unique problems and challenges in design, performance, and interpretation of results. In neutron beam development, different groups use different optimization parameters, resulting in beams being considerably different from each other. The design, development, testing, execution of patient pharmacokinetics and the evaluation of results from these studies differ widely. Finally, the clinical trials involving patient treatments vary in many aspects such as their dose escalation strategies, treatment planning methodologies, and the reporting of data. The implications of these differences in the data accrued from these trials are discussed. The BNCT community needs to standardize each aspect of the design, implementation, and reporting of clinical trials so that the data can be used meaningfully.     

Pharamacokinetic Modeling for Boronophenylalanine-fructose Mediated Neutron Capture Therapy: 10B Concentration Predictions and Dosimetric Consequences

A two-compartment open model has been developed for predicting ¹⁰B concentrations in blood following intravenous infusion of the L-p-boronophenylalanine-fructose complex in humans and derived from pharmacokinetic studies of 24 patients in Phase I clinical trials of boron neutron capture therapy. The ¹⁰B concentration profile in blood exhibits a characteristic rise during the infusion to a peak of 32g/g (for infusion of 350mg/kg over 90min) followed by a biexponential disposition profile with harmonic mean half-lives of 0.32±0.08 and 8.2±2.7h, most likely due to redistribution and primarily renal elimination, respectively. The mean model rate constants k ₁₂, k ₂₁, and k ₁₀ are (mean ± SD) 0.0227±0.0064min^–1, 0.0099±0.0027min^–1, 0.0052±0.0016min^–1, respectively, and the central compartment volume of distribution V ₁ is 0.235±0.042L/kg. In anticipation of the initiation of clinical trials using an intense neutron beam with concomitantly short irradiations, the ability of this model to predict, in advance, the average blood ¹⁰B concentration during brief irradiations was simulated in a retrospective analysis of the pharmacokinetic data from these patients. The prediction error for blood boron concentration and its effect on simulated dose delivered for each irradiation field are reported for three different prediction strategies. In this simulation, error in delivered dose (or, equivalently, neutron fluence) for a given single irradiation field resulting from error in predicted blood ¹⁰B concentration was limited to less than 10%. In practice, lower dose errors can be achieved by delivering each field in two fractions (on two separate days) and by adjusting the second fraction's dose to offset error in the first.     

Solid phase peptide synthesis on hydrophilic supports

Beaded cellulose (Perloza) was modified with acrylonitrile followed by reduction with diborane to give a functionalised support containing aminopropyl groups. This spacer arm was then further extended with a glycolamido or an Fmoc-amino acid-4-oxymethylphenoxyacetyl moiety. A number of peptides, including the Merrifield test peptide leucyl-alanyl-glycyl-valine, leucine-enkephalin, Acyl Carrier Protein (65–74). angiotensin I and II, ACTH(4-11) and LHRH were synthesised on the aminopropyl beaded cellulose support using modified t-butyloxycarbonyl (Boc) or fluorenylmethoxycarbonyl (Fmoc) synthesis protocols. The peptides were cleaved from the support and further purified.     

饮水硼对动物空肠发育的影响

由饮水途径添加硼,研究硼对动物空肠发育的影响。实验取240只1日龄固始鸡,随机分为4组,分别在饮水中添加0、100、200、400 mg/L硼,试验期42 d,每周末每组取试验鸡6只,颈静脉放血致死,取空肠Bouin液固定,制作石蜡切片,HE染色,显微观测、摄影。结果:100 mg/L组空肠绒毛和肠腺的长度显著(P<0.05)或极显著(P<0.01)大于同日龄对照组。400 mg/L组空肠绒毛和肠腺的长度显著(P<0.05)或极显著(P<0.01)小于同日龄对照组(P<0.01)。7～28日龄400 mg/L组空肠出现绒毛上皮细胞肿胀、结缔组织水肿、毛细血管扩张、肠腺囊肿等病变。实验表明:饮水添加100 mg/L硼对固始鸡空肠绒毛及肠腺发育有明显的促进作用;添加400 mg/L硼会引起机体硼中毒,对固始鸡空肠绒毛及肠腺发育有明显抑制和毒害作用,严重影响机体的消化吸收功能。     

Assessment of the results from the phase I/II boron neutron capture therapy trials at the Brookhaven National Laboratory from a clinician's point of view

Summary Boron neutron capture therapy (BNCT) represents a promising modality for a relatively selective radiation dose delivery to the tumor tissue. The key to effective BNCT of tumors such as glioblastoma multiforme (GBM) is the homogeneous preferential accumulation of¹⁰B in the tumor, including the infiltrating GBM cells, as compared to that in the vital structures of the normal brain. Provided that sufficiently high tumor¹⁰B concentration (∼10⁹ boron-10 atoms/cell) and an adequate thermal neutron fluence (∼ 10⁹ neutrons/cm²) are achieved, it is the ratio of the¹⁰B concentration in tumor cells to that in the normal brain cells and the blood that will largely determine the therapeutic gain of BNCT.     

用于硼中子俘获治疗的加速器超热中子源靶的设计

提出适合硼中子俘获治疗加速器^7Li(p,n)^7Be反应中子源一 个金属锂靶的设计，并对中子产额进行了计算。用MonteCarlo的方法研究了中子在水中的慢化和反射层对中子能谱的影响。结果表明，在这种几何结构下^7Li(p,n)^7Be反应产生的中子经过5cm的水层慢化后可作为硼中子俘获治疗的超热中子源。     

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

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.     

Mimicking the magnetic properties of rare earth elements using superatoms

Rare earth elements (REs) consist of a very important group in the periodic table that is vital to many modern technologies. The mining process, however, is extremely damaging to the environment, making them low yield and very expensive. Therefore, mimicking the properties of REs in a superatom framework is especially valuable but at the same time, technically challenging and requiring advanced concepts about manipulating properties of atom/molecular complexes. Herein, by using photoelectron imaging spectroscopy, we provide original idea and direct experimental evidence that chosen boron-doped clusters could mimic the magnetic characteristics of REs. Specifically, the neutral LaB and NdB clusters are found to have similar unpaired electrons and magnetic moments as their isovalent REs (namely Nd and Eu, respectively), opening up the great possibility in accomplishing rare earth mimicry. Extension of the superatom concept into the rare earth group not only further shows the power and advance of this concept but also, will stimulate more efforts to explore new superatomic clusters to mimic the chemistry of these heavy atoms, which will be of great importance in designing novel building blocks in the application of cluster-assembled nanomaterials. Additionally, based on these experimental findings, a novel “magic boron” counting rule is proposed to estimate the numbers of unpaired electrons in diatomic LnB clusters.Searching for low-cost and earth-abundant substitutes to replace precious and scarce elements or materials has become one of the major subjects in cluster science, which has attracted increasing research interest recently (1–5). It has been realized that the number of naturally occurring stable elements remains at 90, even if new elements, which usually have very short half-lives, continue to be added to the periodic table. Among these stable elements, some are very expensive or scarce (e.g., Pt and Au, which are widely applied as precious metal catalysts). Similarly, rare earth elements (REs), which are well-known for their optical and magnetic characteristics, are also expensive. In the meantime, some elements, like silicon, are highly abundant. Therefore, exploring ways to replace these precious or scarce elements in the periodic table is of significance in both fundamental and applied aspects. To achieve this objective, the superatom concept, which is an exciting achievement in cluster science (chosen stable clusters can mimic the chemistry of an atom or a group of the periodic table of elements and yet, retain their integrity when serving as building blocks of new materials), may be helpful. The key findings of this concept came from the experimental investigation of aluminum cluster reactivity performed by Castleman and coworkers in 1989, in which unusual stability was found in Al cluster anions containing 13, 23, and 37 atoms by oxygen-etching experiments (6). Additionally, the Al₁₃ cluster was evidenced to behave like a Cl atom (7–9). Subsequently, in the past decade, extensive investigations have been undertaken to explore and synthesize superatoms using various electron counting rules, and many superatoms have been found that can mimic the chemical properties of halogens, alkaline earth metals, alkalis, and so on (3–5, 7, 10).In the periodic table, REs are a series of chemical elements found in the Earth’s crust that are vital to many modern technologies. One of the most valuable properties of the REs or rare earth-containing compounds is their optical characteristics, which have been widely applied in luminescent nanomaterials, generation and amplification of light in lasers, and optical amplifiers, etc. (11, 12). A popular example is the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (13), which is extensively used in many different fields. Equally important, because of the existence of localized unpaired f electrons, REs are very important components in magnetic materials (e.g., rare earth magnets SmCo₅ and NdFeB) and have attracted much attention recently (14–16). The mining process, however, is extremely damaging to the environment, resulting in the relatively small production, and the consequence is that REs are very expensive. Thus, our interest focuses on exploring novel superatomic clusters that can mimic the properties of the REs, which will be quite significant and valuable. Very recently, by using photoelectron imaging spectroscopy, we showed that the photoelectron spectra of diatomic clusters TiO⁻, ZrO⁻, and WC⁻ are very similar to those of their isovalent anions of group 10 elements, which are Ni⁻, Pd⁻, and Pt⁻, respectively (1). Additionally, the similarity observed in these three isovalent counterparts indicates that, in a number of cases, various atom combinations can lead element mimics by using such a simple but effective isovalent counting rule. It was also found that the similar isovalent characterization and orbital occupation between superatomic clusters and the corresponding elements are two important factors in transition metal mimicry (1, 17). These findings further motivate us to investigate the possibility of rare earth mimicry by using the superatom concept. Unlike the transition metals, as mentioned above, one of the most important properties of the REs is their magnetic characteristics owing to the abundant unpaired electrons. Therefore, finding a superatomic cluster with numbers of unpaired electrons and valence electrons that are similar to those of the corresponding RE is the most important step in mimicking the magnetic properties of REs, which is also the focus of this study. Spectroscopy combined with high-level theoretical calculations has been shown to be a powerful tool to directly examine the electronic structures of atoms and clusters (18–28). Herein, we used photoelectron imaging spectroscopy to explore the possibility of mimicking the magnetic properties of the REs.