Journal of Cancer Research and Therapeutics

: 2016  |  Volume : 12  |  Issue : 2  |  Page : 520--525

Boron neutron capture therapy: Moving toward targeted cancer therapy

Hamid Reza Mirzaei1, Amirhossein Sahebkar2, Rasoul Salehi3, Javid Sadri Nahand4, Ehsan Karimi5, Mahmoud Reza Jaafari6, Hamed Mirzaei7,  
1 Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2 Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
4 Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
5 Department of Clinical Biochemistery, Biochemistry and Nutrition Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
6 Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
7 Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Correspondence Address:
Hamed Mirzaei
Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 91775-1365


Boron neutron capture therapy (BNCT) occurs when a stable isotope, boton-10, is irradiated with low-energy thermal neutrons to yield stripped down helium-4 nuclei and lithium-7 nuclei. It is a binary therapy in the treatment of cancer in which a cytotoxic event is triggered when an atom placed in a cancer cell. Here, we provide an overview on the application of BNCT in cancer therapy as well as current preclinical and clinical evidence on the efficacy of BNCT in the treatment of melanoma, brain tumors, head and neck cancer, and thyroid cancer. Several studies have shown that BNCT is effective in patients who had been treated with a full dose of conventional radiotherapy, because of its selectivity. In addition, BNCT is dependent on the normal/tumor tissue ratio of boron distribution. Increasing evidence has shown that BNCT can be combined with different drug delivery systems to enhance the delivery of boron to cancer cells. The flexibility of BNCT to be used in combination with different tumor-targeting approaches has made this strategy a promising option for cancer therapy. This review aims to provide a state-of-the-art overview of the recent advances in the use of BNCT for targeted therapy of cancer.

How to cite this article:
Mirzaei HR, Sahebkar A, Salehi R, Nahand JS, Karimi E, Jaafari MR, Mirzaei H. Boron neutron capture therapy: Moving toward targeted cancer therapy.J Can Res Ther 2016;12:520-525

How to cite this URL:
Mirzaei HR, Sahebkar A, Salehi R, Nahand JS, Karimi E, Jaafari MR, Mirzaei H. Boron neutron capture therapy: Moving toward targeted cancer therapy. J Can Res Ther [serial online] 2016 [cited 2020 Sep 23 ];12:520-525
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Boron neutron capture therapy (BNCT) is based on the atomic response that happens when boron-10 is irradiated with low-energy thermal neutrons to yield high-direct energy exchange α particles and recoiling lithium-7 (7 Li) cores. The concept of BNCT was first introduced by Locher. They highlighted that neutrons have potentially promising application which could be used as therapeutic agents due to their biological effects.[1],[2] The advancement of the BNCT idea with details has precisely been explored by Barth in 2003.[3] In principle, BNCT enables targeted destruction of harmful cells.[4],[5],[6],[7] It is focused around the atomic catch and splitting responses that happen when boton-10 (10 B), which is a nonradioactive form of naturally occurring boron, is irradiated with low-energy thermal neutrons to yield high-linear energy transfer (LET) particles (helium-4) and withdrawing 7 Li cores.[8],[9] To improve the efficacy of BNCT, a sufficient dose of 10 B must be delivered to the tumor site (f20 Ag/g or f109 particles/cell), and enough thermal neutrons must be devoured by them to keep up a fatal 10 B (n, α)7 Li catch reaction. Since the high-LET particles have limited path lengths in tissue (5–9 µm), the hazardous effects of these high-energy particles are limited to boron holding cells. Clinical interest to use BNCT has been focused in the treatment of high-grade glioma,[3] cerebral metastases [10] and melanoma.[11] BNCT is known as a kind of radiation treatment. In this method,10 B and thermal neutrons are used for tumor tissues. Several studies examined BNCT as an effective method in cancer therapy. In a study, Busse et al. investigated the effect of BNCT on patients with primary and metastatic brain tumors. Their results indicated that tumor volume was reduced following BNCT.[3] This method has the potential for killing tumor cells by thermal energy and 10 B agent.[12],[13],[14] Increasing evidence has shown that BNCT can be combined with drug delivery system strategies such as polymeric particles, liposome and monoclonal antibody (mAb) to increase boron delivery to malignant tissues and cancer cells, particularly when combined with targeted agents (e.g., mAb). This review will cover state-of-the-art findings on radiobiological applications of BNCT, clinical results, and critical issues that must be addressed to increase the efficiency of this treatment modality.

 Application of novel Drug Delivery Systems to Boron Neutron Capture Therapy for Cancer

BNCT has been clinically used for the treatment of dangerous brain tumors, advanced melanomas, head and neck malignancy, and hepatoma.[15],[16] Sodium mercaptoundecahydrododecaborate (Na2 10b12 H11 SH: BSH) and boron phenylalanine (10 BPA) are at present being utilized clinically. Molecular compounds are effortlessly cleared from cancer cells and blood, so high-amassing and specific delivery of boron compounds into tumor tissues and malignancy cells are crucial to accomplish compelling BNCT and to dodge harm to nearby normal cells. With a specific goal to attain the particular delivery of atoms to malignant cells, an efficient drug delivery system is demanded.[17] [Figure 1] shows the schematic representation of various drug delivery systems used for BNCT of cancer.{Figure 1}

Monoclonal antibody

mAb-based treatment of cancer has been secured as a standout among the best helpful techniques for both hematologic malignancies and solid tumors in the recent 20 years.[18],[19],[20],[21] Barth et al. first reported the application of a mAb for boron delivery systems, using boronated mAb 17-1A in potential neutron capture therapy for colorectal cancer.[22] In other study intended to expand the application of BNCT for the treatment of abdominal cancers, it was attempted to determine whether mAb against alpha-fetoprotein (AFP) could be a useful tool to deliver 10 B to AH-66 hepatoma cells for BNCT. Firstly, mAb was boronated by mixing with 10 B-compound (Cs2 10 B12 H11 SH) using N-succinimidyl 3(2-pyridyldithio) propionate. Numbers of 10 B atoms bound to an antibody molecule were proportional to the dose of 10 B-compound added, and the maximum number of 10 B atoms conjugated to an antibody molecule was approximately 1240. After irradiation with thermal neutron, boronated AH-66 cells showed decreasing uptake of (3H) TdR in comparison with the number of 10 B atoms bound to and/or incorporated into the tumor cells. These results indicate that 10 B atoms delivered by moAb exert cytotoxic effects on AH-66 cells in a dose-dependent manner by thermal neutron irradiation.[23] In another research, examined a targeting model of BNCT to hepatoma cells in vivo with a boronated anti (AFP) mAb. This studies shown that the 10 B-conjugated antitumor moAb could deliver a sufficient amount of 10 B atoms to the tumor cells to induce cytotoxic effects 72 h after injection upon thermal neutron irradiation.[24] Tamat et al., in other study, used boronated mAb 225.28S as neutron capture therapy in malignant melanoma.[25] Barth et al. study delivery of boronated epidermal growth factor (EGF) as a molecular targeting agent with utilizing neutron capture therapy in brain tumors. These data shown that the efficacy of BNCT was significantly increased (P < 0.006), following convection-enhanced delivery of boronated dendrimer-EGF compared to intratumoral injection that the survival data were equivalent to those previously reported by using the boronated antihuman-EGF moAb, C225 (cetuximab).[26] [Table 1] illustrates the application of mAbs for boron delivery systems.{Table 1}


The polymers are known as new materials that can be used for drug targeting. Several studies indicated that these agents can be useful for targeting in several tumors such as melanoma, brain tumor, head and neck, and breast.[30] These agents can be produced chemically. They have several properties that increase the utilizing of them in cancer treatment.[17],[31],[32],[33],[34] In an exploration, Shukla et al. examined folic acid conjugates of boronated polyethylene glycol (PEG) containing 3rd generation polyamidoamine dendrimers to obtain 10 B concentrations necessary for BNCT in malignancy by lessening the uptake of these conjugates by the reticuloendothelial framework. Biodistribution studies with this conjugate in C57bl/6 mice bearing folate receptor (+) murine 24jk-FBP sarcomas obtained particular tumor uptake (6.0% ID/g tumor), high hepatic (38.8% ID/g), and renal (62.8% ID/g) uptake, demonstrating that this polymer can be used as delivery system for drug targeting in cancers.[35] In other study, Suzuki et al. studied intrablood vessel organization of sodium borocaptate (BSH)/lipiodol emulsion delivery 10 B to liver tumors exceptionally specifically as BNCT in the rodent liver model. They demonstrated that i.p. administration of BSH/lipiodol emulsion is a successful system for delivering of 10 B specifically to the liver tumors.[36] In other examination, Suzuki et al. examined the pharmacokinetics of BSH succeeding i.p. administration of BSH with other embolizing operator, degradable starch microspheres (DSM). These data showed that BSH/DSM-BNCT was not suitable for the treatment of distinctive liver tumors on account of the low-T/L 10 B fixation degree. Of course, the high-10 B gathering in the liver tumors succeeding intrablood vessel organization of BSH/DSM emulsion recommends that BSH/DSM-BNCT has the potential for procurement to perilous tumors in diverse areas.[37] [Table 2] illustrates the application of polymers as delivery systems of cancer.{Table 2}


Liposomes are widely utilized as carriers for various pharmaceuticals. Furthermore, these carriers can be used for encapsulation to develop delivery systems that can entangle unsteady mixes (for instance, antimicrobials, cell reinforcements, flavors, and bioactive components) and shield their usefulness.[46],[47] Liposomes can trap both hydrophobic and hydrophilic compounds. Hence, they can be used as powerful tools for drug delivery. This system provides suitable environment for different drugs. Liposomes provide effective properties for drugs such as drug targeting, increase half-life, and escape of immune system.[48],[49],[50] Other properties such as biocompatibility, biodegradability, low harmful quality, and bowed to trap both hydrophilic and lipophilic drugs [51] increase the utilizing of these carriers for site-specific drug delivery to tumor tissues.[52],[53],[54] Therefore, liposomes have extended rate both as an investigational system and financially as a drug delivery system.[48],[55],[56] Various studies have been controlled on liposomes with the target of decreasing drug or concentrating on particular cells.[57],[58],[59] Yanagie et al. studied BNCT utilizing 10 B entangled anticarcinoembryonic antigen (CEA) immunoliposome. Their information demonstrated that the immunoliposomes could deliver 10 B molcules to the tumor cells and push cytotoxic impact by thermal neutron. BNCT with immunoliposome may be valuable to the nonresectable threatening tumors in clinical requisition.[60] In other study, Yanagië et al. explored the utilizing of boronated CEA immunoliposome to tumor cell development restraint in vitro by BNCT model. The consequences of this study proposed that immunoliposomes containing the 10 B-compound could go about as a particular and effective transporter of 10 B atoms to target tumor cells by BNCT.[61] In other research, examined inhibition of growth of human breast cancer cells in culture by utilizing of liposomes containing 10 B. This information demonstrated that boronated liposomes can along this line of breast cancer cells in culture to impact cytotoxicity and concealment of development after thermal neutron irradiation.[61] Yanagie et al. examined the using of boron-ensnared stealth liposomes to the hindrance of the development of tumor cells for BNCT in vivo. Their results indicated that intravenous infusion of 10 B-PEG-liposomes can expand the maintenance of 10 B atoms by tumor cells.[62] In other exploration, Maruyama et al. studied intracellular focusing of BSH to suppression tumors by transferrin-PEG liposomes, for BNCT. Their results demonstrated that BSH-typifying TF-PEG liposomes may be helpful as another intracellular targeting carrier in BNCT treatment of diseases.[63] [Table 3] illustrates the application of liposomes and modified liposomes as delivery systems of cancer.{Table 3}

 Clinical Studies of Boron Neutron Capture Therapy for Cancer

Clinical researches BNCT has centered on the treatment of high-grade glioma and either cutaneous primaries or cerebral metastases of melanoma, head and neck and liver tumor.[78],[79],[80] Neutron sources for BNCT as of now are restricted to atomic reactors, and these are accessible in the United States, Japan, a few European countries and Argentina. [Figure 2] illustrates BNCT therapy for different cancer.[30] Various studies indicated that BNCT can be used as a suitable approach in clinical applications. These studies showed that BNCT have a potential for using in clinical.[30] For example, Sköld et al. explored the capability of BNCT, with L-BPA, as first line radiotherapy (RT) for glioblastoma multiforme (GBM). The survival of patients with recently diagnosed GBM from a Stage II BNCT study was contrasted and those from the two arms of a Stage III study with expected RT versus RT in addition to be associative and adjuvant drug with temozolomide (TMZ). A little subgroup, for which the methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) DNA-repair gene was known, was additionally considered. The results showed that the utilization of BNCT with BPA ought to be investigated in a stratified randomized Stage II trial in which patients with the unmethylated MGMT DNA-repair gene are offered BNCT versus RT in addition to TMZ.[81]{Figure 2}


Clinical researches in BNCT have focused primarily on the therapy of high-grade glioma and either cutaneous melanoma, head and neck, thyroid, and liver cancer. BNCT is known as a novel approach for the treatment of various cancers. In addition, this approach may provide suitable and powerful tools in combination with other therapies such as surgery and chemotherapy. With emergence novel drug delivery systems such as polymers, liposomes, and mAbs open new views in treatment cancer with BNCT. These approaches provide effective treatment of BNCT and overcoming to limitations other methods. Finally, two important issues regarding utilizing of BNCT as an approach in cancer therapy remains to be addressed: (i) Insufficient uptake of 10 B-labelled compound within tumor cells and (ii) the lack of efficient imaging methods to monitor the spatial bio-distribution of 10 B-labelled compounds and their pharmacokinetics. BNCT have enhanced because it may become the major modality for the next generation of radiation therapy, cell-selective charged-particle therapy.

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Conflicts of interest

There are no conflicts of interest.


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