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Tissue Uptake of BSH in Patients with Glioblastoma in the EORTC 11961 Phase I BNCT Trial

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Abstract

Purpose: The uptake of the boron compound Na2B12H10-SH (BSH) in tumor and normal tissues was investigated in the frame of the EORTC phase I trial ‘Postoperative treatment of glioblastoma with BNCT at the Petten Irradiation Facility’ (protocol 11961).

Methods and Materials: The boron concentration in blood, tumor, normal brain, dura, muscle, skin and bone was detected using inductively coupled plasma-atomic emission spectroscopy in 13 evaluable patients. In a first group of 10 patients 100 mg BSH/kg bodyweight (BW) were administered; a second group of 3 patients received 22.9 mg BSH/kg BW. The toxicity due to BSH was evaluated.

Results: The average boron concentration in the tumor was 19.9±9.1 ppm (1 standard deviation (SD)) in the high dose group and 9.8±3.3 ppm in the low dose group, the tumor/blood ratios were 0.6±0.2 and 0.9±0.2, respectively. The highest boron uptake has been detected in the dura, very low uptake was found in the bone, the cerebro-spinal fluid and especially in the brain (brain/blood ratio 0.2±0.02 and 0.4±0.2). No toxicity was detected except flush-like symptoms in 2 cases during a BSH infusion at a much higher speed than prescribed.

Conclusion: BSH proved to be safe for clinical application at a dose of 100 mg BSH/kg infused and at a dose rate of 1 mg/kg/min. The study underlines the importance of a further investigation of BSH uptake in order to obtain enough data for significant statistical analysis. The boron concentration in blood seems to be a quite reliable parameter to predict the boron concentration in other tissues.

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Authors and Affiliations

  1. Department of Radiotherapy, University Essen, Germany

    Katalin Hideghéty, Wolfgang Sauerwein & Andrea Wittig

  2. Department of Neurosurgery, Klinikum Großhadern, Munich, Germany

    Claudia Götz

  3. Department of Neurosurgery, Hôpital Pasteur CHU, Nice, France

    Philippe Paquis

  4. Department of Neurosurgery, Zentralkrankenhaus, Bremen, Germany

    Frank Grochulla

  5. Department of Neurosurgery, Karl-Franzens-University, Graz, Austria

    Klaus Haselsberger

  6. Department of Neurosurgery, Vrije Universiteit, Amsterdam, The Netherlands

    John Wolbers

  7. European Commission, Institute for Energy, Joint Research Centre, Italy

    Ray Moss

  8. Nuclear Research and Consultancy Group NRG, Petten, The Netherlands

    Rene Huiskamp

  9. Department of Neurosurgery, CHUV, Lausanne, Switzerland

    Heinz Fankhauser

  10. NDDO Oncology, Amsterdam, The Netherlands

    Martin de Vries

  11. Department of Chemistry, University Bremen, Germany

    Detlef Gabel

Authors
  1. Katalin Hideghéty
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  2. Wolfgang Sauerwein
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  3. Andrea Wittig
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  4. Claudia Götz
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  5. Philippe Paquis
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  6. Frank Grochulla
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  7. Klaus Haselsberger
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  8. John Wolbers
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  9. Ray Moss
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  11. Heinz Fankhauser
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  12. Martin de Vries
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  13. Detlef Gabel
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Hideghéty, K., Sauerwein, W., Wittig, A. et al. Tissue Uptake of BSH in Patients with Glioblastoma in the EORTC 11961 Phase I BNCT Trial. J Neurooncol 62, 145–156 (2003). https://doi.org/10.1023/A:1023201308434

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  • DOI: https://doi.org/10.1023/A:1023201308434

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