File Name: boron chemistry and applications to cancer treatment .zip
- Neutron capture therapy of cancer
- Contemporary Aspects of Boron: Chemistry and Biological Applications, Volume 22
- Neutron Capture Therapy
- Boron Neutron Capture Therapy - A Literature Review
Boron Neutron Capture Therapy BNCT is a radiation science which is emerging as a hopeful tool in treating cancer, by selectively concentrating boron compounds in tumour cells and then subjecting the tumour cells to epithermal neutron beam radiation. The most exclusive property of BNCT is that it can deposit an immense dose gradient between the tumour cells and normal cells. BNCT integrates the fundamental focusing perception of chemotherapy and the gross anatomical localization proposition of traditional radiotherapy. There is an increase in oral cancer burden day by day. The mainstream treatment modalities in treating cancer are surgery, chemotherapy and radiotherapy.
Neutron capture therapy of cancer
Boron Neutron Capture Therapy BNCT is a radiation science which is emerging as a hopeful tool in treating cancer, by selectively concentrating boron compounds in tumour cells and then subjecting the tumour cells to epithermal neutron beam radiation. The most exclusive property of BNCT is that it can deposit an immense dose gradient between the tumour cells and normal cells.
BNCT integrates the fundamental focusing perception of chemotherapy and the gross anatomical localization proposition of traditional radiotherapy. There is an increase in oral cancer burden day by day. The mainstream treatment modalities in treating cancer are surgery, chemotherapy and radiotherapy. Surgical annihilation is highly efficient in primary tumours, but it is limited to surgically sizeable and approachable tumours and thus cancer cells may not be wholely evacuated.
Chemotherapy is the use of chemical drugs to fight cancer. The systemically administrated drugs circulate in the body to kill cells that divide rapidly, especially cancer cells. It commonly has significant side effects due to drug toxicity to normal cells and is subject to the development of resistance by the cancer cells.
Radiation utilizes high energy ionization particles like X-rays, gamma rays or electrons, to damage cells at molecular level and is often used as an integral approach, to exterminate remaining cancer cells after surgery. Gordon Locher was the first one to propose the principle of BNCT in and hypothesized that if boron could be selectively concentrated in a tumour mass and the volume then exposed to thermal neutrons, a higher radiation dose to the tumour relative to adjacent normal tissue would be produced [ 1 ].
BNCT depends on the following nuclear reaction [ 2 ]:. Thus, only neoplastic cells with 10B are ravaged following thermal neutron irradiation. Targeting is primarily achieved by precisely establishing the boron drugs in the tumour rather than by aiming the beam, which provides the explanation for the clinical application of the concept of BNCT.
BNCT integrates the fundamental focusing perception of chemo-therapy and the gross anatomical localization proposition of traditional radiotherapy. The unique outstanding feature of BNCT, is its ability to deposit an immense dose gradient between the tumour cells and normal cells [ 4 ]. This serves as the rationale for its clinical implementation in treating malignant cells, thus sparing normal healthy cells.
The credit of discovery of neutron is attributed to Chadwick in [ 5 ]. Locher in proposed the principal behind the neutron capture reaction, thus the foundation for BNCT evolved from then [ 1 ]. The very first attempt of BNCT was performed in a patient diagnosed with Malignant Glioma in , using the nuclear research reactor presently available in Brookhaven Graphite Research Reactor [ 6 ].
Followed by 3 series of treatment process using BNCT was carried out in 40 patients using simple boron compounds, but they were reported with serious side effects like radio-dermatoses of scalp and deep ulcerations [ 7 ]. Saltkin mentioned that the outcome of BNCT was similar to traditional radiotherapy, causing cerebral oedema and intractable shock in patients [ 8 ]. Sweet WH et al. Asbury AK et al.
Slowly and steadily the rebirth of BNCT took place, but was predominantly limited to countries having research reactor facilities capable of delivering epithermal neutron beam, which had better tissue penetration. BNCT evolved through 60 years of research and clinical progress, but faced n-number of problems including lack of controlled, prospective trials, need of nuclear research reactors for clinical irradiation and disappointment regarding the evolution of ideal boron compounds.
There are three generation boron compounds presently and there has been a constant refinement in each generation of these boron delivery agents, so that these boron compounds achieve more selective targeting of the tumour cell and provide reasonably low toxicity in the living system. These compounds are currently being used in many researches and clinical trials. Low and high molecular weight biomolecules such as mitochondria, lysosomes, endoplasmic reticulum, golgi apparatus, nucleoside, sugars BPA-fructose , porphyrins, liposome and monoclonal antibodies mAb have been used as the tumour targeting moiety.
These 3 rd generation boron compounds tend to work more specifically towards the targeted tumour cell i. These agents are still under research process. Upgradation in Boron Enhancements: There must be sufficient number of boron molecules embedded or incorporated into the tumour cells for their lysis. Thus, to enhance the uptake of boron compounds changes were brought about in the infusion route and rate, for instances in the infusion method intravenous, intra-arterial or direct infusion into the internal carotid artery [ 27 ] were tried.
Combination of boron with other drugs like mannitol was done [ 28 ]. The most promising route that has evolved during the test of time is using tumour targeting moiety and nanoscale drug delivery using liposome and nanoparticles [ 3 ].
The radiation beam which is directed into the tumour bed should have minimal contaminants. Most of these nuclear reactors have already been shut down, or at the verge of closure or have ceased their activities for BNCT trials, only a few are open. ABNS ranging from low-energy electrostatic machines to higher energy cyclotrons and much higher energy Linacs or synchrotrons have been used [ 3 ].
The neutron beam produced by ABNS has a low intensity flux compared to nuclear reactor sources, but there exists a possibility of delivering the neutron sources with the desired intensities by many accelerators.
Moreover, ABNS is compact and less expensive compared to nuclear reactors. Radiotherapy departments in hospitals are quiet well experienced with accelerators for many years. Development in Imaging: An important factor that is often marked as a drawback in BNCT is the heterogeneous boron distribution within the tumour, which causes ambiguity in the calculated dose distributions.
In recent years to follow the pharmacological and chemical behaviour of the boron carrier using PET has become an additional stimulus for BNCT. Already 18F-BPA-PET scan images have been routinely used clinically to assess the distribution of boron molecules in patients by many investigators. The incidence and mortality rates of head and neck cancer are increasing day by day.
Aggressive and combined local treatment including surgery and chemo-radiation has been applied to advanced head and neck cancer, but the prognosis for patients with recurrent disease is generally poor. BNCT is emerging as a hopeful tool in treating cancer, by selectively concentrating Boron compounds in tumour cells and then subjecting the tumour cells to epithermal neutron beam radiation which selectively destroys the tumour cells. The unique property of BNCT is that it can deposit a large dose gradient between the tumour cells and normal cells.
During the earlier days failure of treatment with BNCT were primarily attributable to; a inadequate tumour specificity of boron used as capture agents; b insufficient tissue penetrating properties of the thermal neutron beams and c high blood boron concentrations that resulted in excessive damage to normal brain vasculature and to the scalp [ 34 , 35 ].
It was concluded that BNCT can be used as a rescue therapy in patients with recurrent tumours [ 36 ]. The mean overall survival of the patients was It was concluded that BNCT showed constant endurance of benefit in all cases [ 38 ].
Presently six patients are still alive. The median survival time post BNCT was reported to be It is clearly noticeable that BNCT provides a better ground to treat recurrent malignant meningioma cases successfully [ 39 , 40 ]. The most commonly reported grade 3 toxicities were mucositis, oral pain, fatigue followed by bone necrosis in 3 patients and soft tissue necrosis one patient. Their recent findings demonstrated that after a median follow-up of Their results clearly expose the effectiveness of BNCT [ 24 , 3 ].
The median survival time from the time of BNCT reported was They also stated that BNCT-related morbidity and mortality were acceptably low [ 4 ]. The patient was treated using planned fractionated BNCT twice with 1-month interval to ensure neutron capture in the deep lesion. They had employed epithermal neutron beam as the neutron source and BPA as the boron compound. The radiological studies performed 6 months after the first BNCT showed remarkable shrinkage in tumour size with no evidence of residual tumour [ 43 ].
He also reported tumour growth suppression 2 months after BNCT procedure using BPA as boron delivery agent in a year-old man for recurrent gastric cancer with left cervical node metastasis [ 44 ]. The tumour regressed 7 months after BNCT, with no acute or late adverse effects. The results certainly speaks in favour of BNCT [ 45 ]. He treated two patients diagnosed with EMPD, both were above 70 years of age 73 and 75 years old, respectively.
Complete regression of the tumour was accomplished in both the cases. What was more noteworthy is that, 12 months after BNCT procedure, neither recurrence nor metastasis has been observed in both the cases [ 46 ].
The concept of BNCT though had evolved in , there has been a steady improvement in knowing and understanding the science behind it, working out with the clinical trials and putting it to clinical use. Though may be for now BNCT may not have gained its popularity, but definitely in near future BNCT will be a milestone in the field of radiotherapy for treating cancers. National Center for Biotechnology Information , U.
J Clin Diagn Res. Published online Dec 1. Find articles by Kavitaa Nedunchezhian. Find articles by Nalini Aswath. Find articles by Manigandan Thiruppathy. Find articles by Sarumathi Thirugnanamurthy. Author information Article notes Copyright and License information Disclaimer. Corresponding author. E-mail: ni. This article has been cited by other articles in PMC. Abstract Boron Neutron Capture Therapy BNCT is a radiation science which is emerging as a hopeful tool in treating cancer, by selectively concentrating boron compounds in tumour cells and then subjecting the tumour cells to epithermal neutron beam radiation.
Introduction There is an increase in oral cancer burden day by day. Open in a separate window. Discussion The incidence and mortality rates of head and neck cancer are increasing day by day. Clinical Trials and Investigations 1. Head and Neck Cancers: 1. Other Cancers 2. Conclusion The concept of BNCT though had evolved in , there has been a steady improvement in knowing and understanding the science behind it, working out with the clinical trials and putting it to clinical use.
References  Locher GL. Biological effects and therapeutic possibilities of neutrons. Am J Roentgenol Radium Ther. IAEA in Austria. Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer. Journal of Radiation Research.
The existence of a neutron. Proc R Soc Lond. Neutron capture therapy of gliomas using boron
Contemporary Aspects of Boron: Chemistry and Biological Applications, Volume 22
The boron neutron capture therapy (BNCT) has been utilized for cancer treatment from last decade, where chemotherapy and radiation have.
Neutron Capture Therapy
Abu Ali et al. Chapter 3: Applied Suzuki cross-coupling reaction for syntheses of biologically active compounds V. Dembitsky et al. Chapter 4: Synthesis of selected biologically active compounds via allylboration V.
Boron carbide enriched with 10 B isotope 10 B 4 C was synthesized by simple and low cost solvothermal method. Structural, morphological and optical analysis has been done. Hexagonal phase of the synthesized material show emission in visible region and makes it a promising material for cancer diagnosis. Cytotoxicity analysis has been done to analyze its suitability for biomedical applications. This is a preview of subscription content, access via your institution.
Boron neutron capture therapy BNCT is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10 B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer PCa using an in vivo mouse xenograft model that we have developed.
Boron Neutron Capture Therapy - A Literature Review
Neutron capture therapy NCT is based on the ability of the non-radioactive isotope boron to capture thermal neutrons with very high probability and immediately to release heavy particles with a path length of one cell diameter. This in principle allows for tumor cell-selective high-LET particle radiotherapy. NCT is exciting scientifically but challenging clinically, and a key factor in success is close collaboration among very different disciplines. This book provides a comprehensive summary of the progress made in NCT in recent years. Individual sections cover all important aspects, including neutron sources, boron chemistry, drugs for NCT, dosimetry, and radiation biology.
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Since its first description, boron neutron capture therapy BNCT was a special type of radiotherapy for treatment of cancer and with focus mainly on glioma therapeutic. This procedure requires the selective accumulation of boron into the tumoral cells, and due to this requirement, different boron-enriched compounds have been designed and developed. Efforts to circumvent the selectivity-uptake challenge and other problems, such as solubility, stability, and toxicity, have been to driving force behind the medicinal chemistry field in boron-based compounds. In this regard, a wide diversity of medicinal chemistry hypothesis has been used to obtain new and efficient potential BNCT-glioma drugs. In this chapter, these ideas are analyzed focusing on their medicinal chemistry characteristics.