title: Quantitative subcellular secondary ion mass spectrometry (SIMS) imaging of boron-10 and boron-11 isotopes in the same cell delivered by two combined BNCT drugs: in vitro studies on human glioblastoma T98G cells.
abstract: Ion microscopy was used for subcellular quantitative imaging of the isotopes 10B and 11B in the same cell to evaluate boron delivery using a mixture of two neutron capture therapy drugs, p-boronophenylalanine-fructose (BPA-F) and sodium borocaptate (BSH). The application of 10B-labeled BPA-F and 11B-labeled BSH allowed independent imaging of both 10B and 11B in the same cell using a CAMECA IMS-3f ion microscope. Mixed-drug treatments were compared to single-drug exposures given under identical conditions. 10BPA-F delivered 10B heterogeneously to T98G human glioblastoma cells, with a significantly reduced concentration in an organelle-rich perinuclear region. The intracellular distribution of 11B from 11BSH contrasted with that of the 10B from 10BPA-F, with 11B distributed nearly homogeneously throughout cells. The subcellular distributions of 10B and 11B were sustained in mixed-drug treatments and resembled their localizations after the single-drug treatments. In both single- and mixed-drug treatments, cellular levels of 10B from 10BPA-F nearly doubled between 1 h and 6 h, with a 3:1 intracellular to nutrient medium partitioning, while cellular levels of 11BSH remained essentially unchanged. The net effect of the combined treatment with 10BPA-F and 11BSH was an additive delivery of boron to cells. This study introduces a novel approach for checking potential synergistic, antagonistic or simple additive delivery of two mixed boronated compounds in cellular/subcellular compartments.
authors: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, USA. sc40@cornell.edu
authors: Subhash
authors: S
authors: Chandra
authors: Daniel R
authors: DR
authors: Lorey II
authors: Duane R
authors: DR
authors: Smith
mesh_terms: D001894:Borohydrides / Q000378:metabolism* / Q000494:pharmacology; D001895:Boron / Q000032:analysis* / Q000378:metabolism; D001896:Boron Compounds / Q000378:metabolism* / Q000494:pharmacology; D016754:Boron Neutron Capture Therapy; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D048429:Cell Size; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy; D006801:Humans; D015388:Organelles / Q000187:drug effects; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D011868:Radioisotopes / Q000032:analysis / Q000378:metabolism; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*; D013438:Sulfhydryl Compounds / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: C436045:4-dihydroxyborylphenylalanine; D001894:Borohydrides; D001896:Boron Compounds; D011868:Radioisotopes; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D010649:Phenylalanine; D001895:Boron