Boron Neutron Capture Therapy For Cancer Treatment
Boron in medicine
Boron is a chemical element that is not essential for human health, but it has been studied for its potential medical uses. Some potential uses of boron in medicine include:
The studies about neutrons that Locher published in 1936 has therapeutic applications. Based on the specific boron concentration in tumors and its thermal neutron irradiation, he proposed the BNCT principle. It should be emphasized that tumor tissue receives a larger radiation dose than normal tissue in this situation.
Using the Brookhaven Graphite Research Reactor, the first attempt at BNCT in a patient with malignant glioma was made in 1951, however significant negative impacts were observed. In 1968, results of BNCT clinical studies using sodium borocaptate, where the neutron beam was pointed directly onto the intracranial tumor bed were published in Japan. A 58% 5-year survival rate was attained in this experiment.
This sparked a reemergence of interest in BNCT clinical trials in Europe and the United States. Today, there are a number of BNCT clinics with various types of charged particle accelerators thanks to the efforts of many scientific research groups. Some places where BNTC can be found, listed:
• Helsinki University Hospital (Helsinki, Finland)
• Sumitomo Heavy Industries (Tokyo, Japan)
• Kansai BNCT Medical Center (Osaka, Japan)
• High Energy Accelerator Research Organization
- Osteoporosis treatment:
Some studies have suggested that boron may improve bone density and reduce the risk of osteoporosis, although more research is needed to confirm these findings.
- Cancer treatment:
Some early studies have suggested that boron may have anticancer properties and may be effective in the treatment of certain types of cancer.
-Wound healing:
Boron has been studied for its potential to stimulate wound healing and reduce inflammation.
-Arthritis treatment:
Some studies have suggested that boron may be effective in reducing the symptoms of arthritis, such as pain and inflammation.
-Diabetes treatment:
Boron has been studied for its potential to improve insulin sensitivity and blood sugar control in people with diabetes.
Cancer and treatment methods
Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. There are many different types of cancer, and each type can behave and grow differently.
Treatment for cancer can include surgery, chemotherapy, radiation therapy, and targeted therapy.
The specific treatment recommended for a particular patient will depend on the type and stage of the cancer, as well as the patient's overall health and preferences.
Surgery is a common treatment for cancer that involves removing the cancerous cells or tissue.
Chemotherapy involves the use of medications to kill cancer cells or inhibit their growth. Radiation therapy uses high-energy rays to kill cancer cells or shrink tumors. Targeted therapy involves the use of medications that specifically target certain proteins or genetic changes that are involved in the development and growth of cancer cells.
What is neutron capture therapy?
-Neutron capture therapy is a form of cancer treatment that involves the use of neutron beams to destroy cancer cells. The treatment is based on the fact that cancer cells are often more sensitive to the effects of neutron radiation than normal cells.
-a patient is injected with a compound called a neutron capture agent, which is typically a chemical element that absorbs neutrons easily. The neutron capture agent accumulates in the cancer cells, making them more sensitive to the effects of neutron radiation. The patient is then exposed to a beam of neutrons, which pass through the body and are absorbed by the cancer cells that have taken up the neutron capture agent. The absorbed neutrons cause the cancer cells to break down and die.
Mechanism of BNTC
The nuclear reaction known as boron neutron capture is the foundation of NCT. When the low energy (<0.5 eV) neutrons of the nonradioactive isotope 10B are absorbed, they split apart into an alpha (4He) particle and a recoiled lithium nucleus (7Li). These particles leave behind a lot of energy on their brief path (Fig. 1). A single cell is about 10 μm in size, hence the BNC reaction takes place inside of a single cell. Thermal neutron irradiation of the area can preferentially kill the cancer cells by two heavy particles, 4He and 7Li, produced by the BNC reaction when 10B atoms selectively accumulate in the malignant cells that are surrounded by normal cells [3]. About 1x109 10B atoms per cell, or 20 μg/g of tissue, are needed to cause BNCT (lethal damage).
Accelerators
The emergence of accelerator-based neutron sources has been the most significant development in the therapeutic application of BNCT (ABNS). Although interest in ABNS first developed in the 1980s, it really gained momentum following the Fukushima nuclear disaster in Japan in 2011. With the exception of the Kyoto University Research Reactor Institute at Kumatori, which is no longer in clinical use, this led to the closure of nearly all of Japan's nuclear reactors. In order to treat patients with brain tumors and recurrent tumors of the head and neck, various Japanese businesses, including Sumitomo, Mitsubishi, and Hitachi, have created prototype ABNS that are currently being tested in clinical studies. Essentially, that the clinical outcomes will be at least as satisfactory as those achieved with nuclear reactors.
Unfortunately, this will not persuade doctors who treat cancer patients that BNCT is a desirable cancer therapy option unless specific treatment areas can be pinpointed where BNCT would be a desirable treatment alternative to those that are already available.
Boron neuron capture therapy
-Boron neutron capture therapy (BNCT)
is a type of neutron capture therapy that uses boron-10, a stable isotope of boron, as the neutron capture agent. When boron-10 absorbs a neutron, it becomes boron-11, which is highly radioactive and decays rapidly, releasing high-energy alpha particles. These alpha particles can damage or destroy nearby cells, making BNCT an effective form of cancer treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296588/
Boron compounds
-Ideal compound : high selectivity + low toxicity
- -First-generation compounds: boric acid and its derivatives. These agents were only used in the 1950s and 1960s.
- -Second-generation agents were more selective, had less toxicity included BSH and BPA. Still, only two of these medications have been tested in actual clinical settings.
- -Third-generation compounds are still experimental, but many seem promising for future studies.
https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.601820/full
Third-generation compounds
Boronophenylalanine (BPA)
- -BPA has the structure of phenylalanine that can be recognized mainly by LAT1 amino acid transporters overexpressed on many cancer cells
- -accumulate within a target tumor
- - non toxic
Sodium mercaptoundecahydro-closo-dodecaborate (BSH)
- -In addition to BPA, polyhedral boranes, which contain more boron atoms in a single compound
- -remarkable chemical stability due to the aromatic-like properties
- -cytotoxicity, retention time, and tumor-killing ability were suitable for further clinical trials
Disadvantages of BPA
BPA has a variety of drawbacks, including:
- because it is a derivative of a natural amino acid, it can easily participate in the production of proteins and accumulate in healthy, normal cells.
- a lower solubility (1.6 g L−1 ) than FBPA (2.6 g L−1 ) due to the lipophilic fluorine, FBPA is more soluble in lipids and water.
- Free hydroxyl groups are capable of esterification when they come into contact with the body's glucose and fructose
https://www.iaea.org/publications/15339/advances-in-boron-neutron-capture-therapy
Disadvantages of BSH
-Due to the lack of a recognized biosimilar molecule to BSH, the biggest disadvantage of BSH for the majority of clinical studies is its inability to deliver cancer medicines via receptor-mediated selective transport.
-The cost of using carboranes is high.
BNCT in Cancer Treatment
-The neutron beams selectively kill boron-containing tumor cells while sparing surrounding normal tissue because of the selectivity of delivery agents of 10B to tumor cells.
Future of BNCT
-The primary targets are the creation of a new and more efficient delivery agents or a new method of delivery
-Pharmacological companies and research laboratories should have access to accelerators for large‐scale screening of new, more specific boron delivery agents. Only after the announcement of the results of clinical trials in which all challenges have been overcome will one convincingly be able to say that BNCT is a cancer treatment modality.
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References
1. Kar, Yakup & Şen, Nejdet & Demirbaş, Ayhan. (2006). Boron Minerals in Turkey, Their Application Areas and Importance for the Country's Economy. Minerals and Energy. 20. 2-10. 10.1080/14041040500504293.
2. Dymova, M. & Taskaev, Sergey & Richter, Vladimir & Kuligina, Elena. (2020). Boron neutron capture therapy: Current status and future perspectives. Cancer Communications. 40. 10.1002/cac2.12089.
3. Suzuki M. (2020). Boron neutron capture therapy (BNCT): a unique role in radiotherapy with a view to entering the accelerator-based BNCT era. International journal of clinical oncology, 25(1), 43–50. https://doi.org/10.1007/s10147-019-01480-4
4. Barth, R. F., & Grecula, J. C. (2020). Boron neutron capture therapy at the crossroads - Where do we go from here?. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine, 160, 109029. https://doi.org/10.1016/j.apradiso.2019.109029
5. Fukumitsu, N., & Matsumoto, Y. (2021). Development of an Imaging Technique for Boron Neutron Capture Therapy. Cells, 10(8), 2135. https://doi.org/10.3390/cells10082135
6. Goswami, Avijit & Bandyopadhyay, Anupam & Lamba, Manisha. (2020). A periodic development of BPA and BSH based derivatives in Boron Neutron Capture Therapy (BNCT). Chemical Communications. 57. 10.1039/D0CC06557A.
See also,
https://www.bulbapp.io/p/b474e859-d8ac-4222-bc12-e9058338f1f1/if-carbon-capture-and-storage-is-a-waste-of-time-or-not-?s_id=ad4dd5ad-8188-43a6-8f50-48be646f0593
