title: Capillary electrophoresis-electrospray mass spectrometry and HR-ICP-MS for the detection and quantification of 10B-boronophenylalanine (10B-BPA) used in boron neutron capture therapy.
abstract: Boron neutron capture therapy (BNCT) is a bimodal radiotherapeutic treatment based on the irradiation of neoplastic tissues with neutrons after the tissues have selectively accumulated molecules loaded with nuclides with large neutron capture cross-sections (such boron-10). Boron-10 carriers have been tested to a limited extent, and clinical trials have been conducted on sulfhydryl borane (10B-BSH) and boronophenylalanine (10B-BPA). However, precise and accurate measurements of boron-10 concentrations (0.1-100 microg/g) in specimens and samples of limited size (microg scale) are needed in order to be able to biologically characterise new compounds in predictive tissue dosimetry, toxicology and pharmacology studies as well as in clinical investigations. A new approach based on fast separation and detection of 10B-BPA performed by coupling capillary electrophoresis to electrospray mass spectrometry is reported. This method allows the quantitative analysis and characterisation of 10B-BPA in a short time with a high separation efficiency. Detection limits of 3 microM for 10B-BPA and 30 ng/mL for 10B were obtained with CE-ESI-MS. A quantification limit of 10 microM for 10B-BPA (100 ng/mL for 10B) was attained. The total boron-10 concentration was determined by high-resolution inductively coupled mass spectrometry in order to validate the method. Boron-10 isotope measurements were carried out by HR-ICP-MS at medium resolution (R=4000) due to the presence of an isobaric interference at mass 10. Good agreement was obtained between the values from CE-ESI-MS and those from HR-ICP-MS. The method has been successfully used to determine the 10B-BPA in two lines of cultured cells.
authors.affiliation: European Commission, DG Joint Research Centre, Institute For Transuranium Elements, P.O. Box 2340, 76125, Karlsruhe, Germany.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Pitois
authors.forename: Laura Aldave
authors.initials: LA
authors.lastname: de las Heras
authors.forename: Antonella
authors.initials: A
authors.lastname: Zampolli
authors.forename: Luca
authors.initials: L
authors.lastname: Menichetti
authors.forename: Ramon
authors.initials: R
authors.lastname: Carlos
authors.forename: Guido
authors.initials: G
authors.lastname: Lazzerini
authors.forename: Luca
authors.initials: L
authors.lastname: Cionini
authors.forename: Pietro Alberto
authors.initials: PA
authors.lastname: Salvatori
authors.forename: Maria
authors.initials: M
authors.lastname: Betti
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000032:analysis* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy; D045744:Cell Line, Tumor; D019075:Electrophoresis, Capillary; D042783:Endothelial Cells / Q000737:chemistry* / Q000378:metabolism; D005910:Glioma / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007554:Isotopes; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D051381:Rats; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D001896:Boron Compounds; D007554:Isotopes; D010649:Phenylalanine; C033685:4-boronophenylalanine