Seminar

ATTIA FATIMA Reg. No. 781

M.sc Chemistry 4th Semester

BORON CHEMISTRY AND

APPLICATION TOCANCER TREATMENT

Boron ChemistryBoron is the element of group 13(IIIA), having atomic number 5 and atomic mass 10.811.

First ,Boron was mentioned in book of Persian alchemist Rhazes.

In 1892, French Chemist Henri Moissan produced boron that was 98% pure.

The origin of boron is attributed to Big Bang or galactic cosmic rays events as well as the formation of Li and Be.

ChemistryIt is a semiconductors ,characteristics of both metals and non metals.

The abundance of boron is very low, approximately10-9 times that of hydrogen and around 10-6 of carbon and oxygen.

Physical properties

It occurs in many physical forms called allotropes.

Boron atoms are able to absorb a large number of neutrons.

Two types of isotopes of boron exist,boron-10 and boron-11.Three radioactive isotopes of boron are known also.

ChemistryChemical properties

Boron is not soluble in water. It normally does not react with acids but react with oxygen in the air.

Uses of boron

Boron is used to make alloys and alloys are used to make strong magnets. These magnets are used in microphones, loudspeakers, headphones and switches.

Boron used in nuclear rods for controlling the fast moving neutrons.

Boron is proved to be used in cancer treatment,.Boron-10 particularly.

Boron occurs in many vegetables, fruits and in nuts.

Boron for Cancer

Boron is an element that has proved to be effective in cancer treatment due to its property to absorb the neutrons.

The therapy that is used against cancer treatment is known as Boron Neutron Capture Therapy.

What is cancerCancer is caused by the rapidly dividing abnormal cells that have the potential to reproduce themselves faster than the normal cells.

These rapidly dividing cells form tumors, crowd organs and shut down some organ function.

History of Cancer

Lymph theory developed in 17th century believed on abnormalities in lymphatic system were the cause of cancer.

In 19th century Rudolph Virchow recognized that the cancerous cells derived from other cells.

Other theories described, cancer being caused by the trauma, parasites and it was thought that cancer may spread “like a liquid”.

Karl, a German surgeon concluded that cancer spread through malignant cells.

Cancer and HeredityCancer is disease of abnormal gene function.About 5% to 10% of all cancers are inherited.. Genes that cause cancer called Oncogenes.Top ten Cancer Myths

Hair dye cause brain cancerCell phones cause cancerIf your mom and dad had Cancer, you will have it tooCancer causes hair lossOnly women get breast cancerCancer is almost always fatalWearing antiperspirants and deodorant can cause cancerSome types of cancer can be contagiousPositive thinking will cure cancer

Boron neutron Capture Therapy

BNCT is an ideal technique to kill cancer cells selectively without harming cancer cells which is based on the reaction of non-radioactive boron-10 nuclei capturing slow neutrons to yield high-LET alpha particles, recoiling Li-7 and Gamma rays.

BNCT proposed to treat the patients of glioblastoma multiforme (GBMs). GBMs is a type of malignant tumor of brain involving the glial cells.52% is functional brain tissue and 20% intercrainial tumors.

Also shown its ability to treat other cancers, like neck cancer, liver cancer, melanomas and thyroid cancers since the mid 1980s.

Basic principle

It is a targeted Chemo-radiotherapy.First o all, a boron-10 carrying drug through the blood transportation system. For successful BNCT Blood brain barrier (BBB) is used ,either by passive transport or through the receptor mediated transport..

Thermal neutrons (E=0.025eV) or an epithermal neutron (1eV<E<10keV) used as a source. Nuclear reactors are the source of neutrons.

By the decay of boron atom, Helium-4 nuclei (alpha particle) and Lithium-7 ions to kill the tumor cells.

Boron neutron capture reaction formula (Walker, 1998)

Basic principle

He and Li, particle range within the tumor cells are 9um and 5um (diameter of a tumor cells) respectively.

They have a high linear energy transfer (LET) values as well. Thus high energy released in the tumor cell while normal cells outside the tumor cells survive.

Figure shows the schematic concept of BNCT. (MIT, 2008)

Two Major factors of BNCT

1- Boron-10 delivery agents

2- Neutrons sources

Boron-10 delivery agentsThe primary factor for successful BNCT relies upon the boron-10 delivery agents. There are seven aspects should be considered for a useful boron-10 delivery agent.

1- The important one is the selective accumulative ability to achieve high ratios of (conc. of boron in tumor cells/ conc. of boron in normal cells.

Two major factors of BNCT

2- Low or even none systematic toxicity

3- To achieve at least 20ug B10/g of tumor boron-10

4- Rapid clearance from blood and normal tissues and persistence in tumor during BNCT

5- Chemical stability

6- Water solubility

7- Lipophilicity

Names of delivery agents

1- BPA(4- dihydroxy-borylpheynlalanine)2- Polyhedral boranes [ B10h10]-2 and [B12H12]-23- Sodium decahydrodecaborate Na2B10H10.It proved to be toxic to the human body later on.4- Finally BSH (sulfahydral borane,Na2B12H11SH) with lower toxicity was developed.

Neutrons sources

Two types of neutrons are used for BNCT 1-Thermal neutrons2- Epithermal neutrons

Thermal NeutronsThey have energies of approximately 0.025eV are used in BNCT.Thermal neutrons however cannot penetrate into deep into deep tumors due to only 2.5cm penetration range of them within the tissues surface.

Thus thermal neutrons are suitable for superficial tumor treatments, such as BNCT treatment for melanoma which is type of skin cancer.

Epithermal Neutrons

In order to effectively treat the tumors deep inside the brain without opening crania. Epithermal neutrons have energies (1-10,000eV) beams can deeply penetrate the tissue 3-6cm below the surface.So it can be used to treat deep inside the tumor cells.

At present, neutron beams are extracted from the uranium-235 fission reaction within a nuclear reactor (Walker, 1998).

Clinical trials for cancer treatment

BNCT trials for brain tumorsAt USABNCT was initially proposed to deal with these brain cancers such as glioblastoma multiforme (GBM).BNCT of patients with brain tumors and a few with cutaneous melanoma was resumed in the united states in the mid 1990s at the Brookhaven National Laboratory Medical Research Reactor (BMRR) and at Harvard Institute of Technology (MIT) using MIT research reactor (MITR).

The figure shown below is the CT scans of a patient with GBM.In the right hand figure shown GBM cells of spindle shaped.

Clinical Trials

At JapanMiyatake and Kawabata in Japan have initiated several protocols employing the combination of BPA (500mg/kg) and BSH (100mg/kg) for two hours, followed by neutron irradiation at Kyoto University Research Reactor Institute.

At FinlandThe team of clinicians and physicist at the Helsinki University Central Hospital and VTI Technical Research Central of Finland has reported on 22 patients with malignant gliomas who had undergone standard of their recurrent head and neck cancers and brain tumors have been treated in Finland with BNCT.

Conclusion

BNCT represents a joining together of nuclear technology, chemistry, biology and medicine to treat malignant and recurrent head and neck cancers. Sadly the lack of progress in developing more effective treatment for these tumors has been part of the driving force that continues to propel research in this field. BNCT may be best suited as an adjunctive treatment, used in the combination and external beam radiation therapy for those malignancies, either primary or recurrent, for which there are no effective therapies.