Ion Microscopy Imaging of Boron from BNCT Drugs in Cryogenically Prepared Tissues

  • Duane R. Smith
  • Subhash Chandra
  • Jeffrey A. Coderre
  • Jennifer L. Wilson
  • Peggy L. Micca
  • Marta M. Nawrocky
  • George H. Morrison

Abstract

Histopathologically prepared sections from brain tissue of patients with diseases such as glioblastoma multiforme can reveal satellite regions which are small clusters of malignant cells adjacent to a main tumor mass but embedded in the contiguous healthy brain tissue. Within the BNCT community, as well as the rest of the medical community, it is a well known fact that many of these small tumor satellites cannot be removed during the surgical debulking procedures used to eliminate the main tumor mass. Additionally, the small tumor satellites which remain after surgical treatment are responsible for the regrowth and recurrence of the associated disease. If compounds such as p-boronophenylalanine (BPA) or sodium mercaptoundecahydrododecaborate (BSH) are going to be used successfully in BNCT, then they must selectively target the smallest possible clusters of malignant tumor cells. Thus, it is crucial to provide direct evidence of the selective delivery of boron at the cellular and subcellular level prior to acceptance of these compounds as clinical agents for BNCT. Although analytical techniques such as quantitative neutron capture radiography1 are highly sensitive, they lack the spatial resolution required for analyzing the subcellular distribution of boron. In contrast, ion microscopy is capable of resolving subcellular features such as nucleus, cytoplasm, etc. with a spatial resolution of 0.5 μm.

Keywords

Brush Border Boron Neutron Capture Therapy Optical Microscopy Image Proximal Convoluted Tubule Interlobular Artery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    D. Gabel, H. Holstein, B. Larsson, L. Gille, G. Ericson, D. Sacker, P. Som, and R. G. Fairchild, Quantitative neutron capture radiography for studying the biodistribution of tumor-seeking boron-containing compounds, Cancer Res., 47: 5451–5454, 1987.PubMedGoogle Scholar
  2. 2.
    J. Coderre, P. Rubin, A. Freedman, J. Hansen, T.S. Wooding, Jr., D. Joel, and D. Gash, Selective ablation of rat brain tumors by boron neutron capture therapy, Int. J. Radiation Oncology Biol. Phys., 28 (5): 1067–1077, 1994.CrossRefGoogle Scholar
  3. 3.
    S. Chandra and G.H. Morrison, Ion microscopy in biology and medicine, Methods Enzymol., 158: 157–179, 1988.PubMedCrossRefGoogle Scholar
  4. 4.
    A. Benninghoven, F.G. Rüdenauer, H.W. Werner, “Secondary Ion Mass Spectrometry Basic Concepts, Instrumental Aspects, Applications and Trends,” P.J. Elving, J.D. Einefordner, I.M. Kolthoff, Eds.; Wiley-Interscience, New York, 1987.Google Scholar
  5. 5.
    S. Chandra and G.H. Morrison, Sample preparation of animal tissues and cell cultures for secondary ion mass spectrometry (SIMS) microscopy, Biol. Cell, 74: 31–42, 1992.PubMedCrossRefGoogle Scholar
  6. 6.
    E.W. Sod, A.R. Crooker, and G.H. Morrison, Biological cryosection preparation and practical ion yield evaluation for ion microscopic analysis, J. Microscopy, 160: 55–65, 1990.CrossRefGoogle Scholar
  7. 7.
    S. Chandra and G.H. Morrison, Imaging ion and molecular transport at subcellular resolution by secondary ion mass spectrometry, Int. J. Mass Spec. Ion Proc., 143: 161–176, 1995.CrossRefGoogle Scholar
  8. 8.
    S. Chandra, C.S, Fullmer, C.A. Smith, R.H. Wasserman, and G.H. Morrison, Ion microscopic imaging of calcium transport in intestinal tissue of vitamin D-deficient and vitamin D-replete chickens: a 44Ca stable isotope study, Proc. Natl. Acad. Sci. USA, 87: 5715–5719, 1990.PubMedCrossRefGoogle Scholar
  9. 9.
    J.A. Coderre, T.M. Button, P.L. Micca, C. Fisher, M.M. Nawrocky, and H.B. Liu, Neutron capture therapy of the 9L rat gliosarcoma using the p-boronophenylalanine-fructose complex, Int. J. Radiation Oncology Biol. Phys., 30: 643–652, 1994.CrossRefGoogle Scholar
  10. 10.
    M.S.H. Di Fiore, “Atlas of Human Histology,” 4th ed., Lea and Febiger, Philadelphia, 1974 pp. 172–177.Google Scholar
  11. 11.
    B.D. Bennett, X. Zha, I. Gay, and G.H. Morrison, Intracellular boron localization and uptake in cell cultures using imaging secondary ion mass spectrometry (ion microscopy) for neutron capture therapy for cancer, Biol. Cell, 74: 105–108, 1992.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Duane R. Smith
    • 1
  • Subhash Chandra
    • 1
  • Jeffrey A. Coderre
    • 2
  • Jennifer L. Wilson
    • 1
  • Peggy L. Micca
    • 2
  • Marta M. Nawrocky
    • 2
  • George H. Morrison
    • 1
  1. 1.Department of ChemistryCornell UniversityIthacaUSA
  2. 2.Medical DepartmentBrookhaven National LaboratoryUptonUSA

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