Chandra, S., Lorey, D. R., II and Smith, D. R. 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. Radiat. Res. 157, 700–710 (2002).

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.