Boron neutron capture therapy (BNCT)
The boron neutron capture therapy (BNCT) is a form of cancer radiotherapy. Tumour-targeted compound, containing stable 10B, is first administered to patients, and after the compound with its 10B load has accumulated into tumours, the tissue region is irradiated with low energy (thermal) neutrons. 10B atoms capture neutrons in a 10B (n,α) 7Li reaction. The released α-particles (4He nuclei) and 7Li nuclei, with combined kinetic energy of 2.35 MeV, travel only a very short distance in the tissue, concentrating the ionizations, reactive oxygen species, and radiation damage to the immediate vicinity of the cancer cells (Coderre and Morris, 1999; Wheeler et al., 1999; Barth et al., 2005 and 2018; Miyatake et al., 2016). Boron in nature consists of ∼20% of 10B and ∼80% 11B. Despite the disappointing results of initial patient trials, BNCT has later been successful in the therapy for glioblastoma, melanoma, and head and neck cancers (Kabalka et al., 1997; Coderre and Morris, 1999; Kato et al., 2009; Kawabata et al., 2009; Barth et al., 2012; Kankaanranta et al., 2012). Promising results from BNCT have been obtained in animal models of lung metastases (Andoh et al., 2015) and prostate cancer (Takahara et al., 2015).
Application of BNCT requires availability of neutron source, and therefore BNCT has been available only in institutes with access to nuclear reactor, severely limiting the expansion of this highly useful technique. Accelerator-based neutron sources are being developed (Blue and Yanch, 2003; Kreiner et al., 2016; Miyatake et al., 2016).
Numerous boron carriers have been developed and studied, and two, 4-10B-borono-l-phenylalanine (BPA, L-BPA) (Snyder et al., 1958) and sodium borocaptate (sulfhydryl borane, BSH) are in clinical use (Soloway et al., 1998; Geninatti-Crich et al., 2012; Luderer et al., 2015; Barth et al., 2018; Miyabe et al., 2019). BPA accumulates in tumours mainly by L-type amino acid transporter (LAT1). BSH is taken up in tumours via diffusion (Ishiwata, 2019). Neither of these boron carriers are optimal for BNCT, and new-generation carriers are being developed. Boramino acids (BAAs), where carboxylate group (-COO-) is substituted with isosteric trifluoroborate (-BF3-), are promising ligands for BNCT. BAAs can also be easily labelled with 18F for PET imaging (Liu et al., 2015; Lan et al., 2021).
BNCT may involve administration of very large doses of boron-10 carriers, even >50 g of BPA, and therefore the purity and quality control of the compounds is essential (Dick et al., 2011).
Distribution of BPA in the tissue has been measured using microdialysis (Bergenheim et al., 2005). 10B and 11B are detectable with magnetic resonance, 11B with higher sensitivity and spectral resolution, but 10B with longer T2 relaxation time. The kinetics of racemic BPA, L-BPA, and BSH has been assessed in several MRI studies, mainly in animal models (Ishiwata, 2019). Alternatively, boron carriers can be labelled gadolinium, to be traced with Gd-MRI (Alberti et al., 2018). [18F]FBPA is a fluorine-18 labelled derivative of BPA, which can be used to assess non-invasively the distribution of BPA (and thus boron-10) in the body as a function of time. Similarly, [18F]FBY has been used to assess the distribution of fluoroboronotyrosine (Li et al., 2019; Kong et al., 2022).
Barth RF. A critical assessment of boron neutron capture therapy: an overview. J Neurooncol. 2003; 62(1-2): 1-5. PMID: 12749698.
Barth RF, Zhang Z, Liu T. A realistic appraisal of boron neutron capture therapy as a cancer treatment modality. Cancer Commun. 2018; 38(1): 36. doi: 10.1186/s40880-018-0280-5.
Ishiwata K. 4-Borono-2-18F-fluoro-l-phenylalanine PET for boron neutron capture therapy-oriented diagnosis: overview of a quarter century of research. Ann Nucl Med. 2019; 33: 223-236. doi: 10.1007/s12149-019-01347-8.
Mishima Y (ed.): Cancer Neutron Capture Therapy. Springer, 1996, ISBN 978-1-4757-9569-1. doi: 10.1007/978-1-4757-9567-7.
Moss RL. Critical review, with an optimistic outlook, on Boron Neutron Capture Therapy (BNCT). Appl Radiat Isot. 2014; 88: 2-11. doi: 10.1016/j.apradiso.2013.11.109.
Sauerwein WAG, Wittig A, Moss R, Nakagawa Y (eds.): Neutron Capture Therapy - Principles and Applications. Springer, 2012, ISBN 978-3-642-31334-9. doi: 10.1007/978-3-642-31334-9.
Seki R, Wakisaka Y, Morimoto N, Takashina M, Koizumi M, Toki H, Fukuda M. Physics of epi-thermal boron neutron capture therapy (epi-thermal BNCT). Radiol Phys Technol. 2017; 10(4): 387-408. doi: 10.1007/s12194-017-0430-5.
Updated at: 2022-03-20
Created at: 2004-10-14
Written by: Vesa Oikonen