中子俘获治疗癌症*

简要介绍了中子俘获治疗(NCT ) 的原理、发展历史及最新进展, 指出成功地实现NCT 需要高质量的超热中子束、高选择性的NCT 药物、严格的剂量计算和测量及周密的治疗方案。本文对加速器和反应堆产生超热中子束的两种方法及质量要求作了较详细的讨论, 对BNCT、GdNCT、LiNCT、UNCT 及相关的药物进行了比较性评述, 并对我国开展NCT 研究提出了建议。     

硼中子俘获治疗实验装置射频功率源系统

中国科学院高能物理研究所建造了一台基于加速器的硼中子俘获治疗（BNCT）实验装置。射频功率源系统为352.2 MHz射频四极加速器（RFQ）提供高频功率,使束流离开RFQ时,其能量达到3.5 MeV。BNCT射频功率源系统主要包括速调管功率源、数字低电平控制系统、射频传输系统。本文介绍了BNCT射频功率源系统,主要包括物理需求、系统组成、关键设备、安装和调试。目前该装置已进行动物实验,加速器打靶束流功率4.3 kW,加速器射频功率源系统运行稳定。     

Synthesis,reactivity, in vitro boron neutron capture therapy assay,and molecular docking of fluorocyclocarboxyboranylamine

The one-pot reaction of Me₃NBH₂CN with Et₃O⁺BF₄⁻ followed by addition of BF₃·Et₂O and water produces a trimethylamine derivative of fluorocyclocarboxyboranylamine, Me₃NBH₂C(O₂BF₂NH₂) ( 1 ) in 36.0% yield. Compound 1 undergoes exchange reaction between the exo-Me₃N moiety and piperidine or pyridine to produce the corresponding piperidine-substituted fluorocyclocarboxyboranylamine ( 2 ) or pyridine-substituted fluorocyclocarboxyboranylamine ( 3 ) in 51.2% or 42.4% yields, respectively. The new compounds were characterized by ¹H, ¹³C, ¹¹B, and ¹⁹F nuclear magnetic resonance spectroscopy; Fourier-transform infrared spectroscopy; and elemental analyses and the crystal structure of 1 was determined to confirm its molecular geometry. The in vitro killing effects of 1 , along with its toxicity measurements and molecular docking interactions with matrix metalloproteinases showed a potential promise of such species as both boron neutron capture therapy and boron neutron capture synovectomy agents in the treatment of tumors and rheumatoid arthritis, respectively, in the presence of slow neutrons.     

Syntheses of C-substituted icosahedral dicarbaboranes bearing the 8-dioxane-cobalt bisdicarbollide moiety

The treatment of 1,2-, 1,7- and 1,12-carbaborane lithiated isomers with [3,3′-Co-8-(CH₂CH₂O)₂-(1,2-C₂B₉H₁₀)-(1′,2′-C₂B₉H₁₁)] (1) at molar ratios 1:1 or 1:2 at room temperature in THF leads generally to the formation of a series of orange double-cluster mono and dianions. These were characterized by NMR and MS methods as [1′′-X-1′′,2′′-closo-C₂B₁₀H₁₁]⁻, [2]⁻; [1′′-X-1′′,7′′-closo-C₂B₁₀H₁₁]⁻, [3]⁻ and [1′′-X-1′′,12′′-closo-C₂B₁₀H₁₁], [4]⁻ for the monoanions, whereas [1′′,2′′-X₂-1′′,2′′-closo-C₂B₁₀H₁₀]²⁻, [2]²⁻; [1′′,7′′-X₂-1′′,7′′-closo-C₂B₁₀H₁₀]²⁻, [3]²⁻; and [1′′,12′′-X₂-1′′,12′′-closo-C₂B₁₀H₁₀]²⁻, [4]²⁻ for the dianions (where X = 3,3′-Co-8-(CH₂CH₂O)₂-(1,2-C₂B₉H₁₀)-1′,2′-(C₂B₉H₁₁)). Moreover, these borane-cage subunits can be easily modified via attaching variable substituents onto cage carbon and boron vertices, which makes these compounds structurally flexible potential candidates for BNCT of cancer and HIV-PR inhibition.     

Imaging of atomic and molecular species in tissue with laser‐SNMS for pharmaceutical studies

Successful anticancer therapies will have the ability to selectively deliver compounds to target cells while sparing normal tissue. Currently, methods to determine the distribution of compounds with very high sensitivity and subcellular resolution are still unavailable. Laser secondary neutral mass spectrometry (laser‐SNMS) and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) are capable of detecting atoms and molecules with high sensitivity and a spatial resolution of up to 80 nm. The use of such methods requires special preparation techniques that preserve the morphological and chemical integrity of living cells. In this paper, the ability of laser‐SNMS to study transportation processes in animals of boron‐containing compounds for boron neutron capture therapy will be discussed. The data show that with laser‐SNMS it is possible to measure the distribution of these compounds in tissues with subcellular resolution, and that laser‐SNMS is a very powerful tool for locating anticancer drugs in tissues. Copyright © 2006 John Wiley & Sons, Ltd.     

Boron‐Containing Protoporphyrin IX Derivatives and Their Modification for Boron Neutron Capture Therapy: Synthesis,Characterization, and Comparative In Vitro Toxicity Evaluation

A novel series of boronated porphyrins for potential use in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) for tumor suppression is described. Protoporphyrin IX {i.e., bis(α‐methyl‐β‐pentylethylether)protoporphyrin IX, and bis(α‐methyl‐β‐dodecanylethylether)protoporphyrin IX} bearing polyhedral borane anions (B₁₂H₁₁SH^2?, B₁₂H₁₁NH₃^?, or B₁₂H₁₁OH^2?) were synthesized with reasonable yields. Modification of the protoporphyrin IX structure was achieved by variation of the lengths of the alkyl chains (pentyl and dodecanyl) attached through ether linkages to the former vinyl groups. The goal of this modification was to develop boronated porphyrins with chemical and physical properties that differed from those of protoporphyrin IX. Performance of an MTT assay with each derivative revealed that the synthesized boronated porphyrins showed low cytotoxicities in a variety of cancer cells. Of these compounds, B₁₂H₁₁NH₂^2?‐conjugated porphyrin induced a significant increase in the level of boron accumulation and PDT efficacy against HeLa cells.     

Analysis of 10B antitumoral compounds by means of flow-injection into ESI-MS/MS

Boron neutron capture therapy (BNCT) is a promising binary treatment for cancer. BNCT is based on the ability of the nonradioactive isotope (10)B to capture, with a very high probability, thermal neutrons. This nuclear reaction results in two particles (an alpha and a lithium nucleus). The particles have a high biological effectiveness, which is limited in tissue to approximately the diameter of one cell. If the reaction can be limited to a tumor cell, the physical characteristic opens up the possibility to selectively destroy cancer cells, while sparing the surrounding healthy tissue. Quality control of (10)B-containing compounds and their distribution at present are very important, and different analytical methods have been developed, such as time-of-flight secondary ion mass spectrometry (TOF-SIMS), electron energy loss spectrometry (EELS), prompt gamma analysis and inductively coupled plasma-optical emission spectrometry (ICP-OES). These methods allow the analyses of (10)B, but it is not possible to characterize the specific molecular compounds containing (10)B. For this reason, we propose a fast and quantitative method that permits the determination of closo-undecahydro-1-mercaptododecaborate (BSH) and (10)boron-phenylalanine (BPA) and their eventual metabolites. In particular, (10)B-containing compounds are detected by means of flow-injection electrospray tandem mass spectrometry (FI/ESI-MS/MS). This approach allows the identification of Boron compounds, BSH and BPA, using tandem mass spectrometry, and quantitative analysis is also possible (c.v. +/-4.7%; n = 5; linear range 10-10,000 ng/ml). Furthermore, (10)B-containing compounds were detected in actual biological sample (urine and plasma, diluted 10,000- and 1,000-fold, respectively) injecting a small volume (1 microl) of diluted samples.     

Conjugates of polyhedral boron compounds with carbohydrates. 2. Unexpected easy closo- to nido-transformation of a carborane-carbohydrate conjugate in neutral aqueous solution

A novel 1,2-dicarba-closo-dodecaborane-lactose conjugate 4c, when dissolved in water or methanol, is subject to unexpected deboronation in neutral conditions leading to the formation of the corresponding nido-counterpart (5) as detected by ¹¹B NMR spectroscopy. After heating the aqueous solution of the conjugate 4c at 60 °C for 17 h pure 1,2-dicarba-nido-undecaborane-lactose conjugate 5 was obtained.     

In vivo boron-11 MRI and MRS using (B24H22S2) in the rat

In vivo boron-11 magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were performed on a rat that had been infused with a potential boron neutron capture therapy agent, Na₄B₂₄H₂₂S₂, using methods for detecting nuclei with a short T₂ relaxation time. MRI and MRS were also performed on a euthanized rat that had been similarly infused in vivo. Boron-11 spectral intensities decreased in the living rat over a 25-h period. The results demonstrate the capability of MRI and MRS to noninvasively monitor the distribution and excretion of boron agents in vivo.