BNCT History

BORON NEUTRON CAPTURE THERAPY

BNCT history may be traced back to 1935 (three years after Chadwick discovered neutrons in 1932) when Taylor and Goldhaber [2] described the reaction of thermal neutron capture by 10B boron nucleus. The resulting 11B nucleus decays to an alpha particle (4He) and a 7Li nuclei:

10B + nth →[11B] → α + 7Li + 2.31 MeV    (1)

In 1936  Locher [3] proposed to use the above neutron capture reaction to cure cancer tumours. In 1951 Sweet [4] suggested to treat the most malignant brain tumours with BNCT. The first clinical trials were performed in Brookhaven National Laboratory (BNL) on polymorphic gliomas, soon afterwards some clinical tests were done also in Massachusetts Institute of Technology (MIT). Thermal neutrons of energies <0.4 eV were obtained from research reactors operated by the institutions. Non-selective Borax was used as the boron carrier. The tests were stopped in 1961 in view of unsatisfactory effects:

  • neutrons rather weakly penetrated tissues
  • boron accumulated not only in malignant cells, but also in blood
  • some malignant cells managed to survive even after application of the highest doses permissible from the healthy tissue tolerance point of view
  • scalp and brain blood vessels suffered damages.

A better boron carrier was needed.

Next clinical tests were performed by Hatanaka [5] in Japan in 1968, who introduced BSH, a new boron compound of a better selectivity and ability to concentrate in malignant cells. Hatanaka increased also neutron penetration performing the BNCT procedure intra-operative i.e. on an open scalp (see Fig. 1). The effects were better, however, the obtained survival rate did not differ from that obtained using the conventional therapy. Thermal neutrons could not cure more deeply located tumours. BNCT was then applied to 120 patients.

In the next step neutron energy was increased to the epi-thermal range  (0.4 eV – 10 keV). An increased neutron penetration translated into less damage to surface tissues and higher dose deposited into deeper-located tumours. Advancements in boron carrier technology resulted in development of BPA-f (Borophenylalanine-fructose), a molecule capable to penetrate cell membranes and that way to place boron atoms inside cells. New phase of clinical tests started in 1994 at BNL and MIT. Interest rose also in Europe: starting 1996 the BNCT treatment was tested in Petten (the Netherlands) and in some centres in Finland.

Just like in any other radiotherapy treatment, modern computers and advancements in medical imaging technologies (MRI, PET and the like) have significantly improved BNCT therapy planning. Current topics of research on BNCT include: neutron beam quality improvements, accurate neutron dosimetry, new boron carriers, alternative sources of epithermal neutrons (1 eV – 10 keV) of a deep penetration.

  1. Chadwick, J., (1932), Proc. Roy. Soc. Lond. A, 136, 692-708
  2. Taylor, H. J., Goldhaber M (1935), Nature (Lond.), 135, 341–348
  3. Locher, G. L., (1936), Amer. J. Roentgenol. Radium Ther., 36, 1–13
  4. Sweet, W. H. (1951), The uses of nuclear disintegration in the diagnosis and treatment of brain tumor, New England Journal of Medicine, 245 (23): 875–8, doi: 10.1056/NEJM19511206245230
  5. H. Hatanaka, (1986), Clinical experience of boron-neutron capture therapy for gliomas – a comparison with conventional chemo-immuno-radiotherapy, In: H. Hatanaka ed Boron Neutron Capture Therapy for Tumours. Nishimura Co., Niigata 349-379 http: //www. osaka-u. ac. jp/en/news/ResearchRelease/2013/09/20130906_1
  6. Coderre JA, Morris GM. The radiation biology of boron neutron capture therapy. Radiat Res 1999;151:1–18
  7. Morris GM, Coderre JA, Hopewell JW., et al. Response of the central nervous system to boron neutron capture irradiation: evaluation using rat spinal cord model. Radiother Oncol 1994;32:249–55
  8. Morris GM, Coderre JA, Hopewell JW., Micca PL, Rezvani M. Response of rat skin to boron neutron capture therapy with p-boronophenylalanine or borocaptate sodium. Radiother Oncol 1994;32:144–53