6. Brief History of Boron Neutron Capture Therapy
The first study of charged particles from slow neutron irradiation of boron was
completed at Cambridge University in December 1934
USA used irradiated Boron for cancer treatment
10B + 1n → 7Li + 4He
In 1938, first radiobiological study was carried out by using neutron-10B
reaction at the University of Illinois.
In 1960, Hatanaka in Japan confirmed that BNCT has advantages for patient’s
treatment of certain cancers by comparing between BNCT and conventional
chemo-immuno –radiotherapy
7. History of BNCT
In 1980, a clinical trial was started which concentrated on glioblastoma
multiforme
In 2001, an experiment using BNCT irradiated an explanted liver suffering
from diffuse metastases took place in Italy
In 2003, BNCT used to treat skin melanoma (Nievaart 2007).
8. Basic Principle
Boron is injected to the patient. The uptake of Boron to tumor 20 𝜇g of B/g of
tumor cell
Irradiation of boron through neutron
Non-radioactive B-10 converted in to radioactive B-11
B-11 form Li and He (High LET particles)
He and Le, particle range within the tumor cells are 9µm and 4µm (diameter
of tumor cells ) respectively (Coderre et al., 2004)
L∆ =
∆𝐸
∆𝑙
𝑜𝑟
𝑑𝐸
𝑑𝑙 ∆
9.
10. Mechanism of High LET and Low LET in water hydrolysis
Fig. 1
Fig. 2 Fig. 3
11. Types of Radiation Delivered
Low LET
𝜸 radiation
• Thermal neutron absorbed by H atom of normal tissue
High LET
proton
• Thermal neutron absorbed by N atom
• 14N + 1n →14C + 1H
High LET 𝛼
particle
• Thermal neutron capture and fission reaction with boron
• 10B + 1n → 7Li + 4He
12. Requirements for a successful boron delivery agent
low systemic toxicity and normal tissue uptake with high tumor uptake and
concomitantly high tumor/brain and tumor/ blood concentration ratios
B-10 concentration 20𝜇g /g tumor
Rapid clearance from blood and normal tissues
Retain ability of boron in tumor than normal cells (Barth et al., 2009)
13. Boron delivery agent
Third Generation
stable boron group or cluster which attached by a
hydrolytically stable linkage to a tumor target
Second Generation
[4-dihydroxy-
borylphenylalanine] BPA
sodium mercaptoun decahydro-
closo-dodecaborate (BSH)
First Generation
Boric Acids and its derivatives
14. Optimizing Delivery of Boron-Containing Agents
Delivery of boron agents to brain tumors is dependent on
the plasma concentration profile of the drug, which depends on the amount and
route of administration
the ability of the agent to cross the Blood brain barrier (Lipophilicity)
blood flow within the tumor (Barth et al., 2005)
15. Neutron Source for Boron Neutron Capture Therapy
Nuclear reactor
Reactor produced different energy neutron
a) Thermal Neutron E <0.5ev
b) Epithermal Neutron E <1kev
c) Fast Neutron E >1Kev
17. BNCT uses
Liver cancer
• Hepatic tissue morphology preserved from radiotherapy
• Require heavy operation(auto-transplantation), difficulty of determine
procedure length, fast system for infusion of blood, well trained surgeon
Brain Tumor (Gliomas, Glioblastoma) and Skin cancer (melanomas)
• In Japan BNCT treatment equipment present (50% patient survive)
Lung disease
• Lung tissue are radio-sensitive so conventional therapies are not effective for
its treatment (Barth et al., 2005).
18. Advantages and Disadvantages
Clinical interest in BNCT has focused primarily on the treatment of high-grade
gliomas and melanoma, most recently, head and neck and liver cancer
There are no boron compounds which have a sufficiently high tumor to healthy
tissue ratio, to ensure that healthy tissues will not be affected by BNCT
treatment
Undesirable dose components produced as an unavoidable side-effect (like
gamma rays)
Well trained surgeon (Barth et al., 2009)
19. Cost Analysis
Factors which effect the cost
Cost of nuclear source
Construction of building
Cost of equipment(dosimetry system and CT scan)
Institutional maintenance
Personal cost (depends on number of staff hired)
21. Critical Issues which require improvement
Require more selective and effective boron delivery agents
Radiation dosimetry depends on uptake of boron concentration. Measurement
of accurate, real time dosimetry to better estimate the radiation doses delivered
to the tumor and normal tissues
Need for randomized clinical trial
22. Conclusion
BNCT represents an extraordinary joining together of nuclear technology,
chemistry, biology, and medicine to treat cancer.
The lack of progress in developing more effective treatments for high-grade
gliomas has been part of the driving force that continues to propel research in
this field.
BNCT may be best suited in combination with other modalities, including
surgery, chemotherapy, and external beam radiation therapy, which, when used
together, may result in an improvement in patient survival.
23. References
Bakeine, J. G., M. D. Salvo, S. Bortolussi, S. Stella, P. Bruschi, A. Bertolotti, R. Nano, A. Clerici, C. Ferrari, C.
zonta, A. Marchetti and S. Altieri. 2009. Feasibility study on the ultilization of boron neutron capture therapy
(BNCT) in a rat model of diffuse lung metastases. Applied radiation and isotopes, 67: 332-335.
Barth, F. R., A. Jeffrey, M. Coderre, H. Graa. Vicente, and B. E. Thomas. 2005. Boron Neutron Capture Therapy
of Cancer: Current Status and Future Prospects. A review. Clinical Cancer Research, 11:3987-4002.
Burn, K. W., L. Casalini, E. Nava and R. Tinti. 2006. The epithermal neutron beam for BNCT under construction
at Taprio. Journal of Physics: Conference Series, 41: 187-194.
Coderre, J. A., J. M. Rivard, H. Patel and G. R. Zamenhof. 2004. Topics in Neutron Capture Therapy:
Proceedings of the11thWorld Congress on Neutron Capture Therapy. Applied Radiation Isotopes, 61.
Hentschel, S. J and F. F. Lang. 2005. Current surgical management of glioblastoma. In: Market J, Devita V T,
Rosenberg SA, Hellman S, editors. Glioblastoma multiforme.1sted. Sudbury: Jones and Bartlett Publishers, 108-
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24. Nakagawa, Y., H. Yoshihara, T. Kageji and R. Matsuoka. 2009. Cost analysis of radiotherapy, carbon ion therapy,
proton therapy and BNCT. Applied radiation and isotopes, 67: 80-83.
Nievaart, V.A. 2007. Spectral Tailoring for Boron Neutron Capture Therapy. IOS Press, ISBN 978-1-58603-762-
8.
Parney, I. F and M. S. Chang. 2005. Current chemotherapy for glioblastoma. In: Market J, Devita V T,
Rosenberg S A, Hellman S, editors. Glioblastoma multiforme. 1st ed. Sudbury: Jones and Bartlett Publishers,
161-77.
Parney, I. F., C. Hao and K. Petruk. 2000. Glioma immunology and immunotherapy. Neurosurgery, 46:778-92.
Turiqi, A. A. 2009. Neutron activation boron therapy for cancer treatments. University of Surrey Thesis.
Zonta, T., U. Pinelli, L. Prati, C. Roveda, M. A. Ferrari, C. Clerici, G. Zonta, P. Mazzini, S. Dionigi, S. Altieri, P.
Bortolussi, F. Bruschi and Fossati. 2009. Extra-corporeal liver BNCT for the treatment diffuse metastases.
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