neutron beams for BNCT - Indico
Transcript of neutron beams for BNCT - Indico
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Beams of the “lightest radionuclide useful for hadron therapy”:
neutron beams for BNCT
Maria Pedrosa1,2,
Ignacio Porras2,
Javier Praena2,
M. José Ruiz-Magaña2,
M. Carmen Ruiz-Ruiz2,
Trevor Forsyth1,
Ulli Köster1
1 Institut Laue-Langevin2 Universidad de Granada
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The chart of nuclides
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Boron Neutron Capture Therapy
6% 1.78 MeV – 94% 1.47 MeV
6% 1.01 MeV – 94% 0.84 MeV
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BNCT: radiotherapy selective at cell level
Accumulate the boron in the tumour cells:10B
then
Irradiate with neutrons:
Principle of BNCT
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Effect of Linear Energy Transfer on cell survival
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Comparison of therapies
External beam radiotherapy
X-ray/gamma
protons
carbon ions
LET
/
RBE
Radionuclide therapy
(intravenous)
beta emitter
alpha emitterBNCT
physical localisation
biological localisation
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Comparison of therapies
External beam radiotherapy
X-ray/gamma
protons
carbon ions
LET
/
RBE
Radionuclide therapy
(locoregional)
beta emitter
alpha emitterBNCT
physical localisation
biological localisation
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Glioblastoma multiforme
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Clinical results
Glioblastoma: Recurrent head and neck cancer:
Survival curves of Japanese patients
- Prognosis: 0% survival after 32 months
- With BNCT: 20% still living
- Prognosis: 0% survival after 40 months
- With BNCT: 40% still living
Follow-up/month Follow-up/month
Su
rviv
al%
Su
rviv
al%
- Without BNCT
- With BNCT
- Without BNCT
- With BNCT
S. Miyatake et al. J Neurooncol 91 (2009) 199.
R.F. Barth et al. Radiat Oncol 7 (2012) 146.
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Which boron concentration is required ?
Tolerable neutron fluence: < 21013 cm-2
Probability that one 10B atom captures a neutron:
384010-24 cm2 21013 cm-2 7.710-8
Number of 10B atoms per cell to assure >1 capture/cell:
>> 107
>>10 million boron atoms per cell !
Boron concentration in tumor 30 ppm
Infusion of up to 100 mg BSH/kg or 900 mg BPA/kg
Only metabolic targeting, no receptor targeting!
Tumor/blood ratio: 3
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boron-rich dendrimers with porphyrin nucleus
10 B atoms in each
carborane cage
Also:
- Nanoencapsulation of carboranes
- Nanogels
Boron delivery agents
Until now:
BPA
BSH
New:
Na2B12H11SH
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Which neutron energy is required ?
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Which neutron energy is required ?
E. Bavarnegin et al., JINST 12 (2017) P05005
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Neutron sources for BNCT
Over 700 patients treated at reactors in:
Japan, Finland, Argentina, USA, Netherlands, Sweden, Taiwan…
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Future: accelerators
• Can be integrated into hospitals
• Epithermal neutron spectra from 7Li(p,n) or 9Be(p,n) reactions
• Challenging targetry (10 mA >2 MeV protons)
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?
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Radiobiology knowledge
Gamma 3627
Electron 1113
Alpha 1346
Proton 666
Carbon ions 263
Auger 73
Thermal neutron 68
Neon 66
Pion 46
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Stopping of radiation
Charged particles:
• quasi-continuous stopping
• by Coulomb interaction with
electrons at large distance
• non-destructive detection possible
Neutral particles:
• rare and catastrophic
interaction
• destructive detection
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How dangerous are slow neutrons?
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Neutron RBE
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Reactions relevant for neutron dosimetry
Fast neutrons
(elastic collisions)Gamma emission
(capture on hydrogen)
1H(n,γ) 2H
Thermal neutrons
(capture on nitrogen) Boron capture
1H(n,n’)p
14N(n,p) 14C10B(n,α) 7Li
𝐷𝑓
𝐷𝑡 𝐷𝐵
𝐷𝛾
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𝐷𝑊 – equivalent photon dose
𝐷𝑊 = 𝑤𝑡 𝐷𝑡 + 𝑤𝑓 𝐷𝑓 + 𝑤γ 𝐷𝛾 + 𝑤𝐵 [B10] 𝐷𝐵,1ppm
Both = 3.2 (FiR1), 3.0 (Osaka)
for T and N
• Obtained from very few
experiments
• Strong variability (1.9 – 7.1)
• Difficult to separate
• Assumed equal for
epithermal beams from
reactors (average energy of
fast neutrons ~600 keV)
• Gamma contributions
(substraction assuming
linearity)
Assumed = 1
• D reduction
factor < 1
proposed
because of the
low dose rate
(γ from H
capture)
T = 3.8, N = 1.3,
Skin = 2.5 (BPA)
• Obtained for therapy
of brain tumors =>
applied to H&N
• Compound-
dependent factor
BNCT biological dose
BMRR
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Ele-
ment
Atom
%
Captures Gamma
dose
Recoil
dose
H 62 86% 82% 2%
C 12 0.2% 0.4% 0%
N 1.1 9% 1.7% 98%
O 24 0.0% 0.1% 0%
Cl 0.02 3.4% 12% 0%
A human as neutron target
14C
0.25 m
170 keV/m
p
12 m
12 keV/mMass%
14N(n,p)
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Microscopic nitrogen distribution?
Ele-
ment
Atom
%
Captures Recoil
dose
H 36 15% 0%
C 32 0% 0%
N 35 85% 100%
O 7 0% 0%
Nucleobases
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The ILL Reactor
51018 neutrons/s
generated at 57 MW
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Neutron guides vs. light guides
nvacuum = 1
nwall
nwall
Neutron guide:
nwall < nvacuum = 1
ncore
ncladding
Light guide:
ncore > ncladding > 1
ncladding
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Neutron guides: coated with Ni or multilayer
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Guided neutron beams are “clean”
Fast neutrons and gamma rays are not transported.
H. Abele et al. Nucl. Instr. Meth. A562 (2006) 407.
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The instruments at ILL
Neutrons can be guided with little losses over 100 m.
Bent guides will not transport fast neutrons and
gamma rays clean slow neutron beams.
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Experimental method validated
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ILL’s Deuteration Laboratory
Growth in D2O
Bacteria
Algae
Yeast
Euglena (protiste)
Embryo plants
Mammals
ATOM % D
T. Forsyth,
M. Haertlein, ILL.
Katz and Crespi (1970)
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DBNCT = RBEB x [10B] x DB + D beam + D capt. +
+ RBEfast x Dfast + RBEepi x Depi + RBEth x Dth
RBE factors are derived for a given cell type, dose, dose rate
and end point.
The difficulty of NCT dosimetry
Thermal or cold beam from neutron guide:
DBNCT = RBEB x [10B] x DB + D beam + D capt. +
+ RBEfast x Dfast + RBEepi x Depi + RBEth x Dth
Thermal or cold beam from neutron guide, single cell layer:
DBNCT = RBEB x [10B] x DB + D beam + D capt. +
+ RBEfast x Dfast + RBEepi x Depi + RBEth x Dth
Deuterated cells or 15N enriched cells:
Dth = RBEH x DH + RBEN x DN