Skip to main content
SpringerLink
Log in

Accumulation of Boron in Human Malignant Glioma Cells in vitro is Cell Type Dependent

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

It has been shown that human malignant glioma tumours consist of several subpopulations of tumour cells. Due to heterogeneity and different degrees of vascularisation cell subpopulations possess varying resistance to chemo- or radiation therapy. Therefore, therapy is dependent on the ability to specifically target a tumour cell. Boron neutron capture therapy (BNCT) is a bimodal method, in radiation therapy, taking advantage of the ability of the stable isotope boron-10 to capture neutrons. It results in disintegration products depositing large amounts of energy within a short length, approximately one cell diameter. Thereby, selective irradiation of a target cell may be accomplished if a sufficient amount of boron has been accumulated and hence the cell-associated boron concentration is of critical importance. The accumulation of boron, boronophenylalanine (BPA), was investigated in two human glioma cell subpopulations and a human fibroblast cell line in vitro. The cells were incubated at low boron concentrations (0–5 μg B/ml). Oil filtration was then used for separation of extracellular and cell-associated boron. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used for boron determination. Significant (P < 0.05) differences in accumulation ratio (relation between cell-associated and extracellular boron concentration) between human malignant glioma cell lines were found. Human fibroblasts, used to represent normal cells, showed a growth-dependent uptake and a lower accumulation ratio than the glioma cells. Our findings indicate that BPA concentration, incubation time and differences in boron uptake between cell subpopulations should be considered in BNCT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pontén J, Westermark B: Properties of human malignant glioma cells in vitro. (Review article). Med Biol 56: 184–193, 1978

    PubMed  Google Scholar 

  2. Nistér M, Wedell B, Betsholtz C, Bywater M, Pettersson M, Westermark B, Mark J: Evidence for progressional changes in the human malignant glioma line U-343MGa: analysis of karyotype and expression of genes encoding the subunit chains of platelet-derived growth factor. Cancer Res 47: 4953–4960, 1987

    PubMed  Google Scholar 

  3. Shapiro JR, Mehta BM, Ebrahim SAD, Scheck AC, Moots PL, Fiola MR: Tumor heterogeneity and intrinsically chemoresistant subpopulations in freshly resected human malignant gliomas. In: Sudilovsky O et al. (eds) Boundaries between Promotion and Progression during Carcinogenesis. Plenum Press, New York, 1991

    Google Scholar 

  4. Coderre JA, Morris GM: The radiation biology of boron neutron capture therapy. Radiat Res 151: 1–18, 1999

    PubMed  CAS  Google Scholar 

  5. Gahbauer R, Gupta N, Blue T, Goodman J, Barth R, Grecula J, Soloway AH, Sauerwein W, Wambersie A: Boron neutron capture therapy: principles and potential. Recent Results Cancer Res 150: 183–209, 1998

    PubMed  CAS  Google Scholar 

  6. Barth RF, Soloway AH, Goodman JH, Gahbauer RA, Gupta N, Blue TE, Yang W, Tjarks W: Boron neutron capture therapy of brain tumours — an emerging therapeutic modality. Neurosurgery 44: 433–451, 1999

    Article  PubMed  CAS  Google Scholar 

  7. Fukuda H, Hiratsuka J, Honda C, Kobayashi T, Yoshino K, Karashima H, Takahashi J, Abe Y, Kanda K, Ichihashi M, Mishima Y: Boron neutron capture therapy of malignant melanoma using 10B-paraboronophenylalanine with special reference to evaluation of radiation dose and damage to normal skin. Radiat Res 138: 435–442, 1994

    PubMed  CAS  Google Scholar 

  8. Fukuda H, Honda C, Wadabayashi N, Kobayashi T, Yoshino K, Hiratsuka J, Takahashi J, Akaizawa T, Abe Y, Ichihashi M, Mishima Y: Pharmacokinetics of 10B-p-boronophenylalanine in tumours, skin and blood of melanoma patients: a study of boron neutron capture therapy for malignant melanoma. Melanoma Res 9: 75–83, 1999

    PubMed  CAS  Google Scholar 

  9. Chanana AD, Capala J, Chadha M, Coderre JA, Diaz AZ, Elowitz EH, Iwai J, Joel DD, Liu HB, Ma R, Pendzick N, Peress NS, Shady MS, Slatkin DN, Tyson GW, Wielopolski L: Boron neutron capture therapy for glioblastoma multiforme: interim results from the phase I/II dose-escalation studies. Neurosurgery 44: 1182–1193, 1999

    Article  PubMed  Google Scholar 

  10. Busse PM, Harling OK, Palmer MR, Kiger WS, Kaplan J, Kaplan I, Chuang CF, Goorley JT, Riley KJ, Newton TH, Santa Cruz GA, Lu X-Q and Zamenhof RG: A critical examination of the results from Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease. J Neurooncol 62: 111–121, 2003

    Article  PubMed  Google Scholar 

  11. Capala J, Stenstam H.-B, Sköld K, Munck af Rosenschöld P, Giusti V, Persson C, Wallin E, Brun A, Franzen L, Carlsson J, Salford L, Ceberg C, Persson B, Pellettieri L, Henriksson R: Boron neutron capture therapy for glioblastoma multiforme: clinical studies in Sweden. J Neurooncol 62: 135–144, 2003

    Article  PubMed  Google Scholar 

  12. Joensuu H, Kankaanranta L, Seppala T, Auterinen I, Kallio M, Kulvik M, Laakso J, Vahatalo J, Kortesniemi M, Kotiluoto P, Seren T, Karila J, Brander A, Jarviluoma E, Ryynanen P, Paetau A, Ruokonen I, Minn H, Tenhunen M, Jaaskelainen J, Farkkila M, Savolainen S: Boron Neutron Capture Therapy of brain tumours: clinical trials at the Finnish facility using boronophenylalanine. J Neurooncol 62: 123–134, 2003

    Article  PubMed  Google Scholar 

  13. Snyder HR, Reedy AJ, Lennarz WMJ: Synthesis of aromatic boronic acids. Aldehydo boronic acids and a boronic acid analog of tyrosine. J Am Chem Soc 80: 835–838, 1958

    Article  CAS  Google Scholar 

  14. Coderre JA, Glass JD, Fairchild RG, Micca PL, Fand I, Joel DD: Selective delivery of boron by the melanin precursor analogue p-boronophenylalanine to tumours other than melanoma. Cancer Res 50: 138–141, 1990

    PubMed  CAS  Google Scholar 

  15. Papaspyrou M, Feinendegen LE, Müller-Gärtner H-W: Preloading with L-tyrosine increases the uptake of boronophenylalanine in mouse melanoma cells. Cancer Res 54: 6311–6314, 1994

    PubMed  CAS  Google Scholar 

  16. Sjöberg S, Carlsson J, Ghaneolhosseini H, Gedda L, Hartman T, Malmquist J, Naeslund C, Olsson P, Tjarks W: Chemistry and biology of some low molecular weight boron compounds for boron neutron capture therapy. J Neurooncol 33: 41–52, 1997

    Article  PubMed  Google Scholar 

  17. Mehta SC, Lu RD: Targeted drug delivery for boron neutron capture therapy. Pharm Res 13: 344–351, 1996

    Article  PubMed  CAS  Google Scholar 

  18. Capala J, Makar MS, Coderre JA: Accumulation of boron in malignant and normal cells incubated in vitro with boronophenylalanine, mercaptoborane or boric acid. Radiat Res 146: 554–560, 1996.

    PubMed  CAS  Google Scholar 

  19. Wittig A, Sauerwein WA, Coderre JA: Mechanisms of transport of p-borono-phenylalanine through the cell membrane in vitro. Radiat Res 153: 173–180, 2000

    PubMed  CAS  Google Scholar 

  20. Soloway AH, Tjarks W, Barnum BA, Rong F-G, Barth RF, Codogni IM, Wilson JG: The chemistry of neutron capture therapy. Chem Rev 98: 1515–1562, 1998

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Sweden

    Maria Dahlström, Åke Wasteson & Annelie Lindström

  2. Studsvik Medical AB, Sweden

    Jacek Capala

  3. Unit of Biomedical Radiation Sciences, Uppsala University, Sweden

    Jacek Capala

  4. Department of Physics and Measurement Technology, Linköping Institute of Technology, Linköping University, Sweden

    Peter Lindström

Authors
  1. Maria Dahlström
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacek Capala
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Lindström
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Åke Wasteson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annelie Lindström
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dahlström, M., Capala, J., Lindström, P. et al. Accumulation of Boron in Human Malignant Glioma Cells in vitro is Cell Type Dependent. J Neurooncol 68, 199–205 (2004). https://doi.org/10.1023/B:NEON.0000033489.54011.6b

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NEON.0000033489.54011.6b

Search

Navigation