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The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy

Green, S. and Phoenix, B. and Mill, A. J. and Hill, M. and Charles, M. W. and Thompson, J. and Jones, B. and Ngoga, D. and Detta, A. and James, N. D. and Doran, J. and Graham, N. and Ghani, Z. and Wojnecki, C. and Halbert, G. and Elliott, M. and Ford, S. and Sheehan, T. M. T. and Vickerman, J. and Lockyer, N. and Croswell, G. and Boddy, A. and King, A. and Cruickshank, G. S. (2011) The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy. Clinical Oncology, 23 (3). S23-S24. ISSN 0936-6555

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Abstract

This paper will review progress on two aspects of the Birmingham BNCT project. Firstly on evaluation of the effects of high and low LET radiations when delivered simultaneously, and secondly on attempts to optimise delivery of the boron carrier compound BPA through pharmacokinetic studies. Simultaneous or non-simultaneous irradiations of V79 cells with alpha-particle and X-ray irradiations were performed. Alpha doses of 2 and 2.5 Gy were chosen and the impact on survival when delivered separately or simultaneously with variable doses of X-rays was evaluated. The pharmacokinetics of the delivery of a new formulation of BPA (BPA-mannitol) are being investigated in brain tumour patients through a study with 2 × 2 design featuring intravenous and intracarotid artery infusion of BPA, with or without a mannitol bolus. On the combined effect of low and high LET radiations, a synergistic effect was observed when alpha and X-ray doses are delivered simultaneously. The effect is only present at the 2.5 Gy alpha dose and is a very substantial effect on both the shape of the survival curve and the level of cell killing. This indicates that the alpha component may have the effect of inhibiting the repair of damage from the low LET radiation dose delivered simultaneously. On the pharmacokinetics of BPA, data on the first three cohorts indicate that bioavailability of BPA in brain ECF is increased substantially through the addition of a mannitol bolus, as well as by the use of intracarotid artery route of infusion. In both cases, for some patients the levels after infusion approach those seen in blood, whereas the ECF levels for intravenous infusion without mannitol are typically less than 10% of the blood values.