Boron Neutron Capture Therapy (BNCT) is an experimental radiotherapy technique exploiting the reaction 10B(n,α)7Li to deliver a dose to the tumor sparing the healthy tissues: dedicated molecules are used to introduce the boron selectively in the tumor cells, which are irradiated with a thermal-epithermal neutron beam. There are two main limitations preventing BNCT from becoming a large-scale therapy: the availability of the neutron sources (that for their intensity and energy spectrum are strictly limited to nuclear reactors) and the specificity of the drugs used as boron carriers (i.e. their ability to concentrate only in the cancer cells and not in the bloodstream or in the healthy tissues).

Boron Neutron Capture Therapy (BNCT) is a radiotherapic technique exploiting the α particles produced after the irradiation of the isotope 10 of boron with thermal neutrons in the capture reaction B(n,α)710Li. It is used to treat tumours that for their features (radioresistance, extension, localization near vital organs) cannot be treated through conventional photon-beams radiotherapy. One of the main limitations of this technique is the lack of specificity (i.e. the ability of localizing in tumour cells, saving the healthy tissues) of the compounds used to carry the 10B isotope in the organs to be treated. This work, developed in the framework of the INFN PhoNeS project, describes the possibility of boron imaging performed exploiting the neutrons photoproduced by a linac (the Clinac 2100C/D of the S. Anna Hospital Radiotherapy Unit in Como, Italy) and detecting the αs with a non-depleted microstrip silicon detector: the result is a 1D scan of the boron concentration. Several boron doped samples have been analysed, from solutions of H3BO3 (reaching a minimum detectable amount of 25ng of 10B) to biological samples of urine containing BPA and BSH (the two molecules currently used for the clinical trials in BNCT) in order to build kinetic curves (showing the absolute 10B concentration as a function of time). Further measurements are under way to test the imaging system with 10BPA–Fructose complex perfused human lung samples.

BNCT is a technique exploiting the capture conversion process of thermal neutrons in the reaction B-10(n,alpha)Li-7 to treat extended and radioresistant tumours. One of its main limitations is the lack of specificity of the boron compounds with respect to tumour cells, which needs to be studied with a dedicated neutron beam. This work, developed within the INFN PhoNeS project and carried out at the radiotherapy unit of the S. Anna Hospital in Como with a Varian Clinac 2100C/D, describes the possibility of neutron imaging, performed with the neutrons produced by a Linac detecting the alpha particles with a non depleted self-triggering microstrip silicon detector. Several trials have been made with solutions of B-10 at different percentages, obtaining a minimum sensitivity of 1.9 nmol/cm(2). The paper describes the detector, the measurement setup and the first results with biological samples.

The identification of hemoglobin (Hb) variants is usually performed by means of different analytical steps and methodologies. Phenotypic methods, such as gel electrophoresis and high performance liquid chromatography, are used to detect the different electrophoretic or chromatographic behaviors of hemoglobin variants in comparison to HbA0 used as a control. These data often need to be combined with mass spectrometry analyses of intact globins and their tryptic peptide mixtures. As an alternative to a 'step-by-step' procedure, we have developed a 'single step' approach for the identification of Hb variants present in biological samples. This is based on the microHPLC-ESI-MS/MS analysis of the peptide mixture generated by a tryptic digestion of diluted Hb samples and an in-house new database containing solely the variant tryptic peptide of known human Hb variants. The experimental results (full MS and MS/MS spectra) are correlated with theoretical mass spectra generated from our in-house-built variant peptide database (Hbp) using the SEQUEST algorithm. Simple preparation of samples and an automated identification of the variant peptide are the main characteristics of this approach, making it an attractive method for the detection of Hb variants at the routine clinical level. We have analyzed 16 different samples, each containing a different known variant of hemoglobin.

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.

Boron neutron capture therapy is a promising binary treatment for cancer. It is based on the nuclear fission that occurs when non-radioactive 10B absorbs thermal neutrons. One of the two boron compounds currently used in clinical trials for this therapy is BSH. To ensure differentiated retention in the tumour versus normal tissue prior to treatment, routine analytical methods to determine pharmacokinetics must be available. For this purpose we have developed a new, easy and time saving approach, in which the separation of boron derivatives is performed by means of capillary electrophoresis (CE). The CE method allows analyses to be performed in short times (less than 18 min), sensitively (LOD 8 pg loaded on the capillary) quantitatively (LOQ 5 μg/ml) and with a high efficiency of separation. Moreover it is simpler than HPLC and more reproducible (intra- and inter-day values were ±1% and ±3%, respectively), and does not require a specific column of derivatization. Mass spectrometry analysis of boron derivatives in different samples was also performed to ensure correct attribution of the CE peaks.