Boron Neutron Capture Therapy (BNCT) (Informational)

This is from the National Cancer Institute in a small description. I am posting this as information because at this point it is not widely available. I understand the most activity on this is in Japan.

It seems there is strong renewed interest given the technology improvements. There are quite a few being built around the world, a few in Japan, 1 in Finland, Taiwan, China, etc. and recent data/trials esp for head and neck are very encouraging. The cost came down too…for example in Japan, the treatment costs $20,000 and Japan's national insurance covers $19,000 with only $1,000 out of pocket for patients.

But so far, I haven’t seen it available in the US.

boron neutron capture therapy

(BOR-on NOO-tron KAP-cher THAYR-uh-pee)

A type of radiation therapy. A substance that contains boron is injected into a blood vessel. The boron collects in tumor cells. The patient then receives radiation therapy with atomic particles called neutrons. The neutrons react with the boron to kill the tumor cells without harming normal cells. Boron neutron capture therapy is being studied as a treatment for glioblastoma multiforme and recurrent head and neck cancer. Also called BNCT.

Here is a link to an article about it and there is some more information below.

Here is an article on it from 17 August 2020--

Boron neutron capture therapy: Current status and future perspectives

Abstract

The development of new accelerators has given a new impetus to the development of new drugs and treatment technologies using boron neutron capture therapy (BNCT). We analyzed the current status and future directions of BNCT for cancer treatment, as well as the main issues related to its introduction. This review highlights the principles of BNCT and the key milestones in its development: new boron delivery drugs and different types of charged particle accelerators are described; several important aspects of BNCT implementation are discussed. BCNT could be used alone or in combination with chemotherapy and radiotherapy, and it is evaluated in light of the outlined issues. For the speedy implementation of BCNT in medical practice, it is necessary to develop more selective boron delivery agents and to generate an epithermal neutron beam with definite characteristics. Pharmacological companies and research laboratories should have access to accelerators for large-scale screening of new, more specific boron delivery agents.

1 BACKGROUND

Given that morbidity and mortality of cancer continue to remain at relatively constant levels, we believe that a new cancer therapy, boron neutron capture therapy (BNCT), deserves to be further developed [1]. The prospects for such development and for the clinical implementation of BNCT are promising despite various problems. In particular, the speedy implementation of this method in clinical practice will require the development of more selective boron delivery agents and an epithermal neutron beam with suitable characteristics. This review addresses what in our view are the most important issues relating to the introduction of BNCT. The principles of BNCT and the key milestones in its development are described in details, covering the mechanism of BNCT-induced cell death, the role of BNCT as a treatment modality for different cancers, the characteristics of the currently available boron preparations, and approaches to the delivery of isotope 10B to tumor cells.

2 BNCT

Historical aspects

The existence of the neutron was the first postulated in 1932 by Chadwick [2], who explored the properties of the penetrating radiation emitted from beryllium and boron when bombarded by the alpha particles of polonium. Subsequently, several researchers compared the effects of neutrons and X-rays on normal and tumor tissues. In 1936, Locher [3] published a work about neutrons which had therapeutic possibilities. He proposed the principle of BNCT based on the selective concentration of boron in tumors and its irradiation by thermal neutrons. In this context it is to be noted that tumor tissue receives a higher radiation dose than normal tissue. In 1951, the first attempt at BNCT in a patient with malignant glioma was performed using the Brookhaven Graphite Research Reactor [4]. Thereafter other attempts were made to use BNCT for treatment of cancer patients, but serious adverse effects were encountered, including radiodermatoses of the scalp, cerebral edema, intractable shock, and brain necrosis. Because of poor neutron penetration in deeply seated tumors, in addition to non-selective accumulation of boron compounds in the tumor, these experiments failed. Owing to the toxicity and adverse effects, the United States stopped these clinical trials of BNCT in 1961.

In 1968, Hatanaka reported the results of clinical trials of BNCT in Japan with borocaptate sodium wherein the beam of neutron was aimed directly at the intracranial tumor bed. In this experiment a 5-year survival rate of 58% was achieved [5]. This gave rise to renewed interest in BNCT clinical trials in the United States and Europe. The use of boronophenylalanine as a boron compound was first reported in 1987 in Japan by Mishima, who applied BNCT to treat malignant melanoma [6].

As a result of the efforts of different scientific research groups, today there are several BNCT clinics equipped with different types of charged particle accelerators and targets:

1. A Japanese company, Sumitomo Heavy Industries (Tokyo, Japan) manufactured and installed a cyclotron with an energy of 30 MeV and a current of 2 mA, with a beryllium target, in the Clinic of South Tohoku (Koriyama, Japan) [3]. On 12 March, 2020, Sumitomo Heavy Industries, Ltd. announced that they obtained approval from Japanese Ministry of Health, Labor and Welfare for manufacturing and selling the accelerator-based BNCT system (NeuCure™ System) and the dose calculation program (NeuCure™ Dose Engine). It is worth noting that this approval is valid only for the treatment of unresectable head and neck carcinoma.
2. The University of Tsukuba together with the High Energy Accelerator Research Organization, Japan Atomic Energy Agency, Hokkaido University, Ibaraki Prefecture, and Mitsubishi Heavy Industry Co. have produced an 8-MeV 5-mA linac with a beryllium target for the BNCT clinic in Tokai (Tsukuba, Ibaraki, Japan) [7]. To date, a proton beam with a current of 2 mA has been obtained.
3. The third BCNT clinic is located at the National Cancer Center in Tokyo. Here, a 2.5 MeV linac with a current of 20 mA is used, which was installed by Cancer Intelligence Care Systems, Inc. [8]. To date, a proton beam with a current of 11 mA has been obtained.
4. The fourth BNCT clinic is being built at the Helsinki University Hospital (Helsinki, Finland). For this clinic, Neutron Therapeutics Inc. (Danvers, MA, USA) manufactured a 2.6 MeV, 30 mA direct-acting electrostatic accelerator Hyperion™ with a rotating lithium target and began to assemble it in the fall of 2018. In July 2019, it was announced that Neutron Therapeutics Inc. has agreed with the Tokushukai Medical Group to install a nuBeam system for BNCT at Shonan Kamakura General Hospital in Kamakura, Japan. Clinical trials with involvement of patients with recurrent head and neck cancer will be initiated if the Finnish health authority gives an approval.
5. The fifth BNCT clinic is being built in Xiamen Humanity Hospital (Xiamen, Fujian, China). For this clinic, Neuboron Medtech Ltd. (Nanjing, Jiangsu, China), TAE Life Sciences (Foothill Ranch, CA, USA), and the Budker Institute of Nuclear Physics were commissioned to manufacture a 2.5 MeV, 10 mA tandem accelerator with vacuum insulation and a lithium target, prototypes of which were proposed and developed at the Budker Institute of Nuclear Physics (Novosibirsk, Russia). This facility was expected to enter operation by fall 2019.
6. The sixth clinic is being built in Osaka, Japan. Kansai BNCT Medical Center has a Sumitomo Heavy Industries cyclotron with an energy of 30 MeV and a current of 2 mA, with a beryllium target.

It should be noted that only three accelerators meet the requirements of the International Atomic Energy Agency (IAEA) in respect of current parameters and give a more monochromatic neutron spectrum [9]. The latter is necessary to reduce the adverse effects of γ radiation and thermal neutrons. Another important factor in minimizing the adverse effects of irradiation is the main characteristic of the neutron beam, namely the homogeneous distribution of thermal neutrons in the tumor, including the area around the tumor and areas suspected of harboring tumors. This is because the absorbed dose in a healthy tissue is less than that in a boron-containing tumor tissue. Also, for the production of parallel beams of focused neutrons, a neutron collimator is required. The following accelerators are available: the linac, manufactured by Hitachi; the tandem accelerator with vacuum insulation, manufactured by the Budker Institute of Nuclear Physics; and the direct-acting electrostatic accelerator Hyperion™, manufactured by Neutron Therapeutics. On the other hand, the requirements of IAEA are out of date and need to be revised in accordance with technological progress and development.

Accordingly, today we are witnessing a surge in the development and the clinical research and testing of BNCT based on the use of different types of accelerator. Clinical trials of several accelerators are undergoing: Phase II clinical trials are underway in Japan and trials are soon to be initiated in Finland [1]. The high-tech companies are open to engaging in this process; for example, TAE Life Sciences is developing their own accelerator, which is compact and designed for optimal BNCT delivery. In case of successful clinical trials, BNCT undoubtedly has great prospects for development and implementation in routine practice.

As for its use on the territory of the Russian Federation, it is planned to build a clinic for BNCT in collaboration with the Budker Institute of Nuclear Physics using a tandem accelerator characterized by a proton beam current of 9 mA and an energy of 2.3 MeV [10]. To gain the necessary proton beam, a new type of particle accelerator has been proposed and built – a tandem accelerator with vacuum insulation. With this new accelerator, the values of current and energy required for BNCT have been obtained. A lithium target has been developed and used to generate neutrons. This target contains a thin layer of lithium evaporated over backing, which is being effectively cooled and is radiation-resistant. Targets of this design with some variations are now in use within almost every project. The moderator and compound reflector have been used in the beam-shaping assembly for the first time, thus increasing the quality of the resulting therapeutic neutron beam. Ideas realized in the charged particle accelerator, in the neutron-generating target, and in the beam-shaping assembly are protected by patents. Of course, the constant functioning of these accelerators is accelerating the identification and testing of new boron isotope delivery agents, and their entry into the market.

Take Care, God Bless-Russ