Boron Neutron Capture Therapy
Prof. Mauro Valente, PhD.
Medical Physics – FaMAF
http://www.famaf.unc.edu.ar/~valente/
CONICET & Universidad Nacional de Cordoba
ARGENTINA
The GOAL
It is well known that radiation therapies tray to assess
tumor control by means of killing cancer cells while
sparing health tissues.
Therefore, is there any kind of treatment modality able to
accomplish an “ideal” cancer cell control whereas no
health tissue being affected?
HINT: Radiation damage selectivity
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
2
What is BNCT?
Today Neutron Capture Therapy (NCT) is a promising
form of radiation therapy, which includes 2 interconnected
features:
1. The infusion or delivery of a capture compound, which
preferentially concentrates in the tumor.
2. Then the irradiation of the tumor site by neutrons.
As the isotope 10B is often used as the neutron capture
agent, in this case NCT is called Boron Neutron Capture
Therapy (BNCT).
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
3
Boron Neutron Capture Therapy
7 Li
n th
10 B
a
• Exposure to thermal or epithermal neutrons
• 10B (n,γ) 7Li ( σ = 3837 barn)
• 10B selectively accumulated in tumors
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
4
Why
•
•
10B?
The large cross section of thermal neutron interactions with 10B
isotope (σth ~ 4 000 barn) causes high probability of a slitting of
boron nucleus onto He and Li.
As ionization capability of He and Li ions is high, and their runs
(range) are short, then the cells, preferably enriched by boron, are
killed and the healthy cells are damaged much less.
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
5
BNCT – physical background
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
6
Therapy selectivity
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
7
Neutron Sources
Within patient’s body
fast
neutrons
Neutron
sources

epithermal
neutrons
Moderator
Material
slow
neutrons
Tissue
(moderator)
Cell-killing
10B-Capture in
Tumor
Epithermal neutron (0.4 eV - 10 keV) beams are available
from existing nuclear reactors.
Charged-particle
accelerators,
compact
neutron
generators and hospital radiotherapy facilities for BNCT
(PHONES - INFN) are now under development.

Epithermal neutrons lose energy in the patient body and
become capturable slow (thermalized) neutrons while
proceeding to the tumour.
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
8
Pathologies treated with BNCT
Brain tumor (epithermal)
Melanoma (thermal)
• Fir-1 Espoo Helsinki, Finland
• Massachusetts Institute of Technology
• Brookhaven National Laboratory;
• RA-6 Reactor at the Bariloche Atomic
Center Buenos Aires, Argentina
• Studsvik, Sweden
• High Flux Reactor Petten, Netherlands
• Massachusetts Institute of
Technology
• RA-6 Reactor at the
Bariloche Atomic Center
Buenos Aires, Argentina
Explanted Liver (thermal)
H&N tumor (epithermal)
• Kyoto University Reasearch Reactor,
Japan
• Triga Mark II reactor Pavia,
Italy
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
9
BNCT facilities around the world
UK
MIT
Budker
& IPPE
Mainz
LBL
LNL
Japan
Japan
Pavia
Beijing
CNEA
RA-6
CNEA
Reactors
Accelerators (under study)
07/04/2015
Mauro
Valente,
PhD.
Algunos
conceptos
de Radiobiologia
de
Prof. Mauro
Valente
- CONICET
&
BNCT
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
10
10
Treatment facility for BNCT
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
11
Treatment facility for BNCT: explanted liver
Spheroidal Holder for Liver Treatment at the HFR (Petten)
Liver holder placed in PMMA block
Block and holder placed in graphite cage
Beam-eye view of final configuration,
covered with polyethylene sheet
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
12
BNCT facility for explanted liver
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
13
BNCT main features
Neutron reactions in tissue without 10B:
Thermal Neutrons:
1H(n,)2H
 = 0.33 b
E = 2.2 MeV
14N(n,p)14C
 = 1.9 b
E(p) = 0.63 MeV
Epithermal and fast neutrons:
elastic scattering
pmainly with H
(backscattering p+)
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
14
BNCT
BNCT constitutes a mixed field radiation therapy modality,
therefore:
RADIOBIOLOGY
The study and characterization of ionizing
radiation effects on biological systems
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
15
15
BNCT
IONIZING RADIATION
DIRECT IONIZING
• Charged particles, like electrons, protons, alpha particles, muons
and heavy ions, which cause ionization by means of
electromagnetic interactions and producing direct atom/molecule
ionizations. The penetration capacity (range) is low.
INDIRECT IONIZING
• Non charged particles, like photons and neutrons, which cause
ionization by means of a two step mechanism consisting on a first
excitation of charged particles and further ionizations and energy
transfer to the irradiated media. The penetration capacity (mean
free path) is high.
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
16
16
BNCT & equivalent dose
Mixed field modality
LINEAR ENERGY TRANSFER (LET)
• Low LET radiations, like photons, induce only a little quantity of
ionizations along the track while traveling within the irradiated
material.
• High LET radiation produces high ionization density per unit
track, which significantly increases the biological effectiveness
(lethal & sublethal radiation damage).
Relative Biological
Effectiveness (RBE)
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
17
17
High vs low LET radiation damage
Direct damage
Indirect damage
High LET
Low LET
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
18
18
Temporal scale of radiation damage
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
19
19
Characteristics of nuclear reaction 10B(n,α)7Li
Particle
type
Energy
(MeV)
Range
(μm)
α
1.47
9
Mean
LET
(keV/μm)
196
7Li
0.84
5
162
... What about X-rays?
LET (60Co) ~ 0.2 keV/μm & LET (250 keV) ~ 2 keV/μm
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
20
How to “deliver” 10B to tumoral cells?
Different boron compound are commercially available as good candidate for carrier agents
whitout contamination/biohazard risks for patient health:
 Na2B12H11SH mercaptoundecahydrododecaborate (BSH)
 Boronophenylalanine (BPA)
Both of them have proved to be non dangerous for patient treatment within the
administration range (12-90 μg per g for BPA and 20-120 μg per g for BSH).
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
21
21
Typical radiation source characterization
Neutron beam type
Spectral range
Thermal
En < 0.5 eV
Epithermal
0.5eV<En< 10 keV
Fast
En > 10 keV
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
22
22
Typical radiation source characterization
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
23
23
Dosimetric properties of BNCT
Radiation field on tissue during BNCT irradiation is constituted by 3
main contributions of significant different LET and therefore different
RBE:
• Low LET photons (γ rays) arrising mainly from neutron capture in H
within the tissue [1H(n,γ)2H].
• High LET 1H arrising from scattering of fast neutrons and neutron
capture in N [14N(n,p)14C].
• High LET 4He particles nd 7Li ions resulting from the neutron.induced
fission reaction [10B (n,α ) 7Li].
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
24
24
Dosimetric properties of BNCT
Total Dose
Fast n0
Total γ dose
10B
1H:
dose
(uniformly
distributed)
n0 capture
in N
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
25
25
Dosimetric properties of BNCT
Dose-rates in the central axis of a phantom containing 10 ppm of 10B
and a simulated tumor with 35 ppm of 10B
0 ,1 5
Fast neutrons
N e u tro n i ve lo c i
TOTAL
Photons
F o to n i
D o se R ate (G y/m in )
N e u tro n i te rm ic i
Thermal neutrons
B o ro (1 0 p p m in N , 3 57p p m in T )
0 ,1
Boron (a and Li)
E le ttro n i (2 8 .6 p p m in N , 1 0 0 p p m in T )
Electrons
T o ta le in T e s s u to
PHOTONS
Total
0 ,0 5
AUGER
ELECTRONS
0
FAST
0
NEUTRONS
4
TUMOR
8
12
D e p th (c m )
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
26
26
Dosimetric properties of BNCT
… do you remember our initial goal-question?
Is there any kind of treatment modality able to accomplish an
“ideal” cancer cell control whereas no health tissue being affected?
BNCT seems to be an excellent candidate
… but, what kind of “magic” dosimetric method may be able for 3D
dose contribution quantification in the mixed BNCT field?
I hope to offer you an answer in the next talk!!
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
27
27
Boron Neutron Capture Therapy
Prof. Mauro Valente, PhD.
Medical Physics – FaMAF
http://www.famaf.unc.edu.ar/~valente/
CONICET & Universidad Nacional de Cordoba
ARGENTINA
THANKS FOR YOUR KIND ATTENTION!!!
Mauro
Valente,- CONICET
PhD.
Prof. Mauro
Valente
&
http://www.famaf.unc.edu.ar/~valente/
Universidad Nacional de Cordoba
28
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