The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform

Duane R. Smith - One of the best experts on this subject based on the ideXlab platform.

  • 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.
    Radiation research, 2002
    Co-Authors: Subhash Chandra, Daniel R. Lorey, Duane R. Smith
    Abstract:

    Abstract 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 co...

  • Quantitative Imaging and Microlocalization of Boron-10 in Brain Tumors and Infiltrating Tumor Cells by SIMS Ion Microscopy: Relevance to Neutron Capture Therapy
    Cancer research, 2001
    Co-Authors: Duane R. Smith, Subhash Chandra, Rolf F. Barth, Weilian Yang, Darrel D. Joel, Jeffrey A. Coderre
    Abstract:

    Boron neutron capture therapy (BNCT) is dependent on the selective accumulation of Boron-10 in tumor cells relative to the contiguous normal cells. Ion microscopy was used to evaluate the microdistribution of Boron-10 from p-Boronophenylalanine (BPA) in the 9L rat gliosarcoma and the F98 rat glioma brain tumor models. Four routes of BPA administration were used: i.p. injection, intracarotid (i.c.) injection [with and without blood-brain barrier disruption (BBB-D)], and continuous timed i.v. infusions. i.p. injection of BPA in the 9L gliosarcoma resulted in a tumor-to-brain (T:Br) Boron-10 concentration ratio of 3.7:1 when measured at the tumor-normal brain interface. In the F98 glioma, i.c injection of BPA resulted in a T:Br ratio of 2.9:1, and this increased to 5.4:1 when BBB-D was performed. The increased tumor Boron uptake would potentially enhance the therapeutic ratio of BNCT by >25%. At present, ion microscopy is the only technique to provide a direct measurement of the T:Br Boron-10 concentration ratio for tumor cells infiltrating normal brain. In the 9L gliosarcoma, this ratio was 2.9:1 after i.p. administration. In the F98 glioma, i.c injection resulted in a ratio of 2.2:1, and this increased to 3.0:1 after BBB-D. Ion microscopy revealed a consistent pattern of Boron-10 microdistribution for both rat brain tumor models. The Boron-10 concentration in the main tumor mass (MTM) was approximately twice that of the infiltrating tumor cells. One hour after a 2-h i.v. infusion of BPA in rats with the 9L gliosarcoma, tumor Boron-10 concentrations were 2.7 times higher than that of infiltrating tumor cells [83 ± 23 μg/g tissue versus 31 ± 12 μg/g tissue (mean ± SD)]. Continuous 3- and 6-h i.v. infusions of BPA in the 9L gliosarcoma resulted in similar high Boron-10 concentrations in the MTM. The Boron-10 concentration in infiltrating tumor cells was two times lower than the MTM after a 3-h infusion. After 6 h, the Boron-10 concentration in infiltrating tumor cells had increased nearly 90% relative to the 2- and 3-h infusions. A 24-h i.v. infusion resulted in similar Boron-10 levels between the MTM and the infiltrating tumor cells. Boron concentrations in the normal brain were similar for all four infusion times (∼20 μg/g tissue). These results are important for BNCT, because clinical protocols using a 2-h infusion have been performed with the assumption that infiltrating tumor cells contain equivalent amounts of Boron-10 as the MTM. The results reported here suggest that this is not the case and that a 6-h or longer infusion of BPA may be necessary to raise Boron-10 levels in infiltrating tumor cells to that in the MTM.

H. Patel - One of the best experts on this subject based on the ideXlab platform.

  • Analysis of Boron‐10 in soft tissue by dynamic secondary ion mass spectrometry
    Journal of microscopy, 2004
    Co-Authors: A. C. Oyedepo, S. L. Brooke, Peter J Heard, John C. Day, Geoffrey C. Allen, H. Patel
    Abstract:

    We report here a preliminary study in which dynamic secondary ion mass spectrometry (SIMS) has provided images of Boron-10 ( 1 0 B) in biological tissue as used in research into Boron neutron capture therapy. Cultured tumour cells incubated in media containing known concentrations of a 1 0 B-containing compound, p-Boronophenylalanine (BPA), and intracranial tumour tissue from animals previously injected with BPA were analysed by an in-house constructed SIMS. Investigations were conducted in positive secondary ion detection mode using a 2 5-keV. 5-nA gallium primary ion source. For calibration purposes, tissue standards were also analysed and their Boron-to-carbon signal ratios correlated to bulk Boron concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Ion maps of 1 0 B, 1 2 C, 2 3 Na and 3 9 K showing gross tissue and cell features were acquired. SIMS and ICP-AES standard measurements were in good agreement. Tissue regions with high or low 1 0 B concentrations were identified along with 1 0 B hotspots in normal brain areas. Cultured cells revealed the intracellular localization of 1 0 B. SIMS is capable of producing images showing the distribution of 1 0 B at p.p.m. levels in cells and in normal and tumour-bearing brain tissue.

Subhash Chandra - One of the best experts on this subject based on the ideXlab platform.

  • 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.
    Radiation research, 2002
    Co-Authors: Subhash Chandra, Daniel R. Lorey, Duane R. Smith
    Abstract:

    Abstract 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 co...

  • Quantitative Imaging and Microlocalization of Boron-10 in Brain Tumors and Infiltrating Tumor Cells by SIMS Ion Microscopy: Relevance to Neutron Capture Therapy
    Cancer research, 2001
    Co-Authors: Duane R. Smith, Subhash Chandra, Rolf F. Barth, Weilian Yang, Darrel D. Joel, Jeffrey A. Coderre
    Abstract:

    Boron neutron capture therapy (BNCT) is dependent on the selective accumulation of Boron-10 in tumor cells relative to the contiguous normal cells. Ion microscopy was used to evaluate the microdistribution of Boron-10 from p-Boronophenylalanine (BPA) in the 9L rat gliosarcoma and the F98 rat glioma brain tumor models. Four routes of BPA administration were used: i.p. injection, intracarotid (i.c.) injection [with and without blood-brain barrier disruption (BBB-D)], and continuous timed i.v. infusions. i.p. injection of BPA in the 9L gliosarcoma resulted in a tumor-to-brain (T:Br) Boron-10 concentration ratio of 3.7:1 when measured at the tumor-normal brain interface. In the F98 glioma, i.c injection of BPA resulted in a T:Br ratio of 2.9:1, and this increased to 5.4:1 when BBB-D was performed. The increased tumor Boron uptake would potentially enhance the therapeutic ratio of BNCT by >25%. At present, ion microscopy is the only technique to provide a direct measurement of the T:Br Boron-10 concentration ratio for tumor cells infiltrating normal brain. In the 9L gliosarcoma, this ratio was 2.9:1 after i.p. administration. In the F98 glioma, i.c injection resulted in a ratio of 2.2:1, and this increased to 3.0:1 after BBB-D. Ion microscopy revealed a consistent pattern of Boron-10 microdistribution for both rat brain tumor models. The Boron-10 concentration in the main tumor mass (MTM) was approximately twice that of the infiltrating tumor cells. One hour after a 2-h i.v. infusion of BPA in rats with the 9L gliosarcoma, tumor Boron-10 concentrations were 2.7 times higher than that of infiltrating tumor cells [83 ± 23 μg/g tissue versus 31 ± 12 μg/g tissue (mean ± SD)]. Continuous 3- and 6-h i.v. infusions of BPA in the 9L gliosarcoma resulted in similar high Boron-10 concentrations in the MTM. The Boron-10 concentration in infiltrating tumor cells was two times lower than the MTM after a 3-h infusion. After 6 h, the Boron-10 concentration in infiltrating tumor cells had increased nearly 90% relative to the 2- and 3-h infusions. A 24-h i.v. infusion resulted in similar Boron-10 levels between the MTM and the infiltrating tumor cells. Boron concentrations in the normal brain were similar for all four infusion times (∼20 μg/g tissue). These results are important for BNCT, because clinical protocols using a 2-h infusion have been performed with the assumption that infiltrating tumor cells contain equivalent amounts of Boron-10 as the MTM. The results reported here suggest that this is not the case and that a 6-h or longer infusion of BPA may be necessary to raise Boron-10 levels in infiltrating tumor cells to that in the MTM.

A. C. Oyedepo - One of the best experts on this subject based on the ideXlab platform.

  • Analysis of Boron‐10 in soft tissue by dynamic secondary ion mass spectrometry
    Journal of microscopy, 2004
    Co-Authors: A. C. Oyedepo, S. L. Brooke, Peter J Heard, John C. Day, Geoffrey C. Allen, H. Patel
    Abstract:

    We report here a preliminary study in which dynamic secondary ion mass spectrometry (SIMS) has provided images of Boron-10 ( 1 0 B) in biological tissue as used in research into Boron neutron capture therapy. Cultured tumour cells incubated in media containing known concentrations of a 1 0 B-containing compound, p-Boronophenylalanine (BPA), and intracranial tumour tissue from animals previously injected with BPA were analysed by an in-house constructed SIMS. Investigations were conducted in positive secondary ion detection mode using a 2 5-keV. 5-nA gallium primary ion source. For calibration purposes, tissue standards were also analysed and their Boron-to-carbon signal ratios correlated to bulk Boron concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Ion maps of 1 0 B, 1 2 C, 2 3 Na and 3 9 K showing gross tissue and cell features were acquired. SIMS and ICP-AES standard measurements were in good agreement. Tissue regions with high or low 1 0 B concentrations were identified along with 1 0 B hotspots in normal brain areas. Cultured cells revealed the intracellular localization of 1 0 B. SIMS is capable of producing images showing the distribution of 1 0 B at p.p.m. levels in cells and in normal and tumour-bearing brain tissue.

Rolf F. Barth - One of the best experts on this subject based on the ideXlab platform.

  • Quantitative Imaging and Microlocalization of Boron-10 in Brain Tumors and Infiltrating Tumor Cells by SIMS Ion Microscopy: Relevance to Neutron Capture Therapy
    Cancer research, 2001
    Co-Authors: Duane R. Smith, Subhash Chandra, Rolf F. Barth, Weilian Yang, Darrel D. Joel, Jeffrey A. Coderre
    Abstract:

    Boron neutron capture therapy (BNCT) is dependent on the selective accumulation of Boron-10 in tumor cells relative to the contiguous normal cells. Ion microscopy was used to evaluate the microdistribution of Boron-10 from p-Boronophenylalanine (BPA) in the 9L rat gliosarcoma and the F98 rat glioma brain tumor models. Four routes of BPA administration were used: i.p. injection, intracarotid (i.c.) injection [with and without blood-brain barrier disruption (BBB-D)], and continuous timed i.v. infusions. i.p. injection of BPA in the 9L gliosarcoma resulted in a tumor-to-brain (T:Br) Boron-10 concentration ratio of 3.7:1 when measured at the tumor-normal brain interface. In the F98 glioma, i.c injection of BPA resulted in a T:Br ratio of 2.9:1, and this increased to 5.4:1 when BBB-D was performed. The increased tumor Boron uptake would potentially enhance the therapeutic ratio of BNCT by >25%. At present, ion microscopy is the only technique to provide a direct measurement of the T:Br Boron-10 concentration ratio for tumor cells infiltrating normal brain. In the 9L gliosarcoma, this ratio was 2.9:1 after i.p. administration. In the F98 glioma, i.c injection resulted in a ratio of 2.2:1, and this increased to 3.0:1 after BBB-D. Ion microscopy revealed a consistent pattern of Boron-10 microdistribution for both rat brain tumor models. The Boron-10 concentration in the main tumor mass (MTM) was approximately twice that of the infiltrating tumor cells. One hour after a 2-h i.v. infusion of BPA in rats with the 9L gliosarcoma, tumor Boron-10 concentrations were 2.7 times higher than that of infiltrating tumor cells [83 ± 23 μg/g tissue versus 31 ± 12 μg/g tissue (mean ± SD)]. Continuous 3- and 6-h i.v. infusions of BPA in the 9L gliosarcoma resulted in similar high Boron-10 concentrations in the MTM. The Boron-10 concentration in infiltrating tumor cells was two times lower than the MTM after a 3-h infusion. After 6 h, the Boron-10 concentration in infiltrating tumor cells had increased nearly 90% relative to the 2- and 3-h infusions. A 24-h i.v. infusion resulted in similar Boron-10 levels between the MTM and the infiltrating tumor cells. Boron concentrations in the normal brain were similar for all four infusion times (∼20 μg/g tissue). These results are important for BNCT, because clinical protocols using a 2-h infusion have been performed with the assumption that infiltrating tumor cells contain equivalent amounts of Boron-10 as the MTM. The results reported here suggest that this is not the case and that a 6-h or longer infusion of BPA may be necessary to raise Boron-10 levels in infiltrating tumor cells to that in the MTM.

  • Boronated starburst dendrimer monoclonal antibody immunoconjugates evaluation as a potential delivery system for neutron capture therapy
    Bioconjugate Chemistry, 1994
    Co-Authors: Rolf F. Barth, Albert H. Soloway, Dianne M. Adams, F. Alam, Michael V Darby
    Abstract:

    Boron neutron capture therapy (BNCT) is based on the nuclear capture reaction that occurs when Boron-10, a stable isotope, is irradiated with low-energy or thermal neutrons ( [11B]-->4He(alpha) + 7Li + 2.39 MeV]. Approximately 10(9) Boron-10 atoms must be delivered to each target cell in order to sustain a lethal 10B(n,alpha)7Li reaction. If MoAbs are to be used for targeting Boron-10, then it is essential that they recognize a surface membrane epitope that is highly expressed on tumor cells and that a large number of Boron-10 atoms be attached to each antibody molecule. In order to heavily Boronate MoAbs, we have utilized starburst dendrimers (SD), which are precise, spherical macromolecules composed of repetitive poly(amidoamino) groups. Second- and fourth-generation dendrimers, having 12 and 48 reactive terminal amino groups and molecular weights of 2414 and 10,632 Da, respectively, were Boronated using an isocyanato polyhedral borane, Na(CH3)3NB10H8NCO. The Boronated starburst dendrimers (BSD), in turn, were derivatized with m-maleimidobenzoyl N-hydroxysulfosuccinimide ester (sulfo-MBS). The MoAbIB16-6, which is directed against the murine B16 melanoma, was derivatized with N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP). The MBS-derivatized BSD and SPDP-derivatized MoAb were reacted to yield stable immunoconjugates.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Delivery of Boron-10 for Neutron Capture Therapy by Means of Monoclonal Antibody - Starburst Dendrimer Immunoconjugates
    Progress in Neutron Capture Therapy for Cancer, 1992
    Co-Authors: Rolf F. Barth, Albert H. Soloway, Dianne M. Adams, F. Alam
    Abstract:

    The use of monoclonal antibodies (MoAbs) for the delivery of radionuclides, drugs and toxins for therapeutic purposes has been the subject of intensive investigation over the past decade. A few investigators, including ourselves, have focused on the possible use of MoAbs directed against tumor associated antigens (TAA) for targeting Boron-10 to tumors1,2. Using a high molecular weight macromolecule, poly-DL-lysine and a methyl isocyanato-polyhedral borane, Na(CH3)3 NB10H8NCO, we have prepared a Boronated polylysine (BPL) containing 23% Boron by weight and having > 1700 Boron atoms per polymeric unit3. This Boronated macromolecule was then attached to MoAbs utilizing two heterobifunctional reagents N-succinimidyl 3-(2 pyridyldithio) propionate (SPDP), which was used to introduce potential sulfhydryl groups into proteins, and sulfo mmaleimidobenzoyl-N-hydroxysuccinimide ester (sMBS), which was used to introduce maleimido groups on MoAbs4. The resulting immunoconjugates retained a high degree of in vitro immunoreactivity but had lost their in vivo tumor localizing properties5. It became apparent that an alternative approach was required to produce Boron containing immunoconjugates that would retain both their immunoreactivity and in vivo tumor localizing properties6. The purpose of the present report is to describe our most recent efforts to prepare Boron containing immunoconjugates using a neutrally charged precision macromolecule consisting of repetitive polyamido amino groups(PAMAM) arranged in a starburst pattern (“starburst” dendrimers)7.