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

S. Green, B. Phoenix, A. J. Mill, M. Hill, M. W. Charles, J. Thompson, B. Jones, D. Ngoga, A. Detta, N. D. James, J. Doran, N. Graham, Z. Ghani, C. Wojnecki, G. Halbert, M. Elliott, S. Ford, T. M. T. Sheehan, J. Vickerman, N. Lockyer & 4 others G. Croswell, A. Boddy, A. King, G. S. Cruickshank

Research output: Contribution to journalSpecial issue

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.
LanguageEnglish
PagesS23-S24
Number of pages2
JournalClinical Oncology
Volume23
Issue number3
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Boron Neutron Capture Therapy
Mannitol
Linear Energy Transfer
Pharmacokinetics
X-Rays
Radiation
Boron Compounds
Arteries
Alpha Particles
Survival
Therapeutics
Intravenous Infusions
Brain Neoplasms
Biological Availability
Brain

Keywords

  • clinical oncology
  • BNCT
  • birmingham boron neutron capture therapy
  • project
  • selective internal particle therapy
  • developments

Cite this

Green, S., Phoenix, B., Mill, A. J., Hill, M., Charles, M. W., Thompson, J., ... Cruickshank, G. S. (2011). The Birmingham Boron Neutron Capture Therapy (BNCT) project: developments towards selective internal particle therapy. Clinical Oncology, 23(3), S23-S24. https://doi.org/10.1016/j.clon.2011.01.378
Green, S. ; Phoenix, B. ; Mill, A. J. ; Hill, M. ; Charles, M. W. ; Thompson, J. ; Jones, B. ; Ngoga, D. ; Detta, A. ; James, N. D. ; Doran, J. ; Graham, N. ; Ghani, Z. ; Wojnecki, C. ; Halbert, G. ; Elliott, M. ; Ford, S. ; Sheehan, T. M. T. ; Vickerman, J. ; Lockyer, N. ; Croswell, G. ; Boddy, A. ; King, A. ; Cruickshank, G. S. / The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy. In: Clinical Oncology. 2011 ; Vol. 23, No. 3. pp. S23-S24.
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author = "S. Green and B. Phoenix and Mill, {A. J.} and M. Hill and Charles, {M. W.} and J. Thompson and B. Jones and D. Ngoga and A. Detta and James, {N. D.} and J. Doran and N. Graham and Z. Ghani and C. Wojnecki and G. Halbert and M. Elliott and S. Ford and Sheehan, {T. M. T.} and J. Vickerman and N. Lockyer and G. Croswell and A. Boddy and A. King and Cruickshank, {G. S.}",
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Green, S, Phoenix, B, Mill, AJ, Hill, M, Charles, MW, Thompson, J, Jones, B, Ngoga, D, Detta, A, James, ND, Doran, J, Graham, N, Ghani, Z, Wojnecki, C, Halbert, G, Elliott, M, Ford, S, Sheehan, TMT, Vickerman, J, Lockyer, N, Croswell, G, Boddy, A, King, A & Cruickshank, GS 2011, 'The Birmingham Boron Neutron Capture Therapy (BNCT) project: developments towards selective internal particle therapy' Clinical Oncology, vol. 23, no. 3, pp. S23-S24. https://doi.org/10.1016/j.clon.2011.01.378

The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy. / Green, S.; Phoenix, B.; Mill, A. J.; Hill, M.; Charles, M. W.; Thompson, J.; Jones, B.; Ngoga, D.; Detta, A.; James, N. D.; Doran, J.; Graham, N.; Ghani, Z.; Wojnecki, C.; Halbert, G.; Elliott, M.; Ford, S.; Sheehan, T. M. T.; Vickerman, J.; Lockyer, N.; Croswell, G.; Boddy, A.; King, A.; Cruickshank, G. S.

In: Clinical Oncology, Vol. 23, No. 3, 04.2011, p. S23-S24.

Research output: Contribution to journalSpecial issue

TY - JOUR

T1 - The Birmingham Boron Neutron Capture Therapy (BNCT) project

T2 - Clinical Oncology

AU - Green, S.

AU - Phoenix, B.

AU - Mill, A. J.

AU - Hill, M.

AU - Charles, M. W.

AU - Thompson, J.

AU - Jones, B.

AU - Ngoga, D.

AU - Detta, A.

AU - James, N. D.

AU - Doran, J.

AU - Graham, N.

AU - Ghani, Z.

AU - Wojnecki, C.

AU - Halbert, G.

AU - Elliott, M.

AU - Ford, S.

AU - Sheehan, T. M. T.

AU - Vickerman, J.

AU - Lockyer, N.

AU - Croswell, G.

AU - Boddy, A.

AU - King, A.

AU - Cruickshank, G. S.

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

KW - clinical oncology

KW - BNCT

KW - birmingham boron neutron capture therapy

KW - project

KW - selective internal particle therapy

KW - developments

U2 - 10.1016/j.clon.2011.01.378

DO - 10.1016/j.clon.2011.01.378

M3 - Special issue

VL - 23

SP - S23-S24

JO - Clinical Oncology

JF - Clinical Oncology

SN - 0936-6555

IS - 3

ER -