1 1 מ חויבות ל מ צוינות - ג רעין להצלחה bnct and other studies at soreq...
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1 רעין להצלחהג - צוינותמל חויבותמ
BNCT and other studies at Soreq
EuCARD2 kickoff meeting
Ido Silverman for SARAF team
14/6/2013
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2 רעין להצלחהג - צוינותמל חויבותמ
SARAF GoalsTo enlarge the experimental nuclear science
infrastructure and promote the research in Israel
To develop and produce radioisotopes primarily for bio-medical applications
To modernize the source of neutrons at Soreq and extend neutron based research and applications
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3 רעין להצלחהג - צוינותמל חויבותמ
Neutron yield from d and p beams In the range of tens of MeV projectiles, neutron yield from
deuterons is higher than that of protons by a factor of 3-5
K. van der Meer, M.B. Goldberg et al. NIM B (2004)
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4 רעין להצלחהג - צוינותמל חויבותמ
SARAF Accelerator requirements Low energy – moderate accelerator cost
Deuterons – be efficient in neutron production – enable neutron-rich isotope production
Protons – common isotopes production
High intensity – a n flux similar to the IRR1 TNR image plane
Variable energy – be specific in isotopes production
CW – avoid thermal stress in targets
Pulsed – enable beam tuning with space charge (using slow pulses)
Low beam loss – enable hands-on maintenance
superconducting RF linear accelerator
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5 רעין להצלחהג - צוינותמל חויבותמ
Parameter Value Comment
Ion Species Protons/Deuterons
M/q ≤ 2
Energy Range 5 – 40 MeV Variable energy
Current Range
0.04 – 5 mA CW (and pulsed)
Operation 6000 hours/year
Reliability 90%
Maintenance Hands-On Very low beam lossPhase I - 2009 Phase II - 2019
SARAF Accelerator Complex
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6 רעין להצלחהג - צוינותמל חויבותמ
A. Nagler, Linac2006K. Dunkel, PAC 2007 C. Piel, PAC 2007 C. Piel, EPAC 2008 A. Nagler, Linac 2008J. Rodnizki, EPAC 2008J. Rodnizki, HB 2008 I. Mardor, PAC 2009A. Perry, SRF 2009
I. Mardor, SRF 2009L. Weissman, DIPAC 2009L. Weissman, Linac 2010J. Rodnizki, Linac 2010D. Berkovits, Linac 2012L. Weissman, RuPAC 2012
SARAF phase-I linac - upstream view
SARAF phase-I linac – upstream view
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7 רעין להצלחהג - צוינותמל חויבותמ
EIS
LEBT RFQPSM
MEBTPhase I - 2009
D-plate
Beam line - 2010 targets
Beam dumps
SARAF Q1 2013
Linac is operated routinely with CW 1mA protons at ~4 MeV Phase I commissioned to 50% duty cycle 4.8 MeV deuterons The accelerator is used most of the time to:
Study high intensity beam tuning Interface with high intensity targets Develop of high intensity targets
7 m
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8 רעין להצלחהג - צוינותמל חויבותמ
SARAF applicationsThermal neutrons source for radiography and
diffraction
Radio-isotopes production laboratory
Fast neutron source
aBNCT
Radiation damage studies
Basic physics research with radioactive beams
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9 רעין להצלחהג - צוינותמל חויבותמ
Thermal neutron source
TNR
Diffractometer
Thermal neutron source
9Be(d,xn)
beam
6 m
Thermal Neutron Radiography (TNR)
2 mA deuteron beam @ 40 MeV100 cm2 Beryllium target106 n/s/cm2 on the detector
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10 רעין להצלחהג - צוינותמל חויבותמ
Production of radio-pharmaceutical isotopes Today, most radiopharmaceutical isotopes are
produced by protons Deuterons
Production of neutron-rich isotopes via the (d,p) reaction (equivalent to the (n,g) reaction)
Typically, the (d,2n) cross section is significantly larger than the (p,n) reaction, for A>~100
Hermanne Nucl. Data (2007)
I. Silverman et al. NIM B (2007)
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11 רעין להצלחהג - צוינותמל חויבותמ
Radioisotopes Medical Use
64Cu (β+) 89Zr (β+) 111In (γ) 124I (β+) Diagnostics
68Ge (68Ga – β+) 99Mo (99mTc – γ) DiagnosticsGenerator
67Cu (β-) 103Pd (X-rays) 177Lu (β-)
186Re (β-) 211At (α) 225Ac (α)Therapy
Currently Preferred Options
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12 רעין להצלחהג - צוינותמל חויבותמ
Production of 68Ge.
S. Halfon et al. AccApp11 conference (2011)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60
Proton energy (MeV)
Yiel
d ( m
Ci/(m
A·h)
)
69Ga(p,2n)68Ge
Physical properties
Half-life = 68 min
Positron branching 89% (PET nuclide)
Available via 68Ge/68Ga generator
Parent 68Ge cyclotron produced (T½= 271 d)
Chemical properties of Gallium
Trivalent metal
Chelation chemistry
Applicability
Short half-life useful for molecules with fast biokinetics (peptides, Ab-fragments, small complexes,…)
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13 רעין להצלחהג - צוינותמל חויבותמ
Lutetium-177Application of Lutetium-177
Currently, produced in reactors via 176Lu (n,g)177Lu;
Use for therapy with ability to employ dosimetry;
Labeling: peptides, proteins and antibodies.
Physical properties
Half-life = 6.7 days
Eb- = 490 keV / Eg = 113 keV (3%), 210 keV (11%)
Targe LinkerSST 177Lu
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14 רעין להצלחהג - צוינותמל חויבותמ
*Hermanne A., et al, Int. Conf. on Nuc. Data for Science and Tec. 1355-1358 (2007)
Activity (EOB)
Irritation Time Current / flux
Target Type Facility
3000 Ci/gr 7 d 3*1013 n/cm2s Enriched Lu-176 Reactor
222 Ci 200 h 5 mA Enriched Yb-176 SARAF
28 Ci 200 h 5 mA Natural Yb SARAF
Production of 177Lu in SARAF Via 176Yb(d,x)177Lu (21MeV); The production of Lu-177 can be carried out only by
deuterons! The product is carrier-free (No Lu-176 or Lu-177m) Collaboration of Soreq NRC and Hadassah Medical
Organization, Jerusalem;
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15 רעין להצלחהג - צוינותמל חויבותמ
Why Alpha? Effective cell-killing due to high LET (100 keV/m);
Penetration (40-80 m) ideal for killing -metastases without compromising neighboring healthy tissues;
Effective under hypoxic conditions;
Does not require high dose-rate (1 mCi);
The damage to the DNA is non-repairable;
The cytotoxic effectiveness of a-particles is negligible and does not depend on the cell cycle status.
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16 רעין להצלחהג - צוינותמל חויבותמ
225Ac – Advantages 225Ac: T½ = 10 days; 213Bi: T½ = 46 min; 4 a-emission at each decay (6 MeV) – high efficiency; Ability to employ dosimetry; Can be produced by SARAF at high yields.
225Ac: clinical trials phase I: AML; 213Bi: clinical trials phase I: AML, malignant, melanoma, Non-
Hodgkin's lymphoma, NET; 225Ac & 213Bi: preclinical trials: Neuroblastoma, Breast,
Prostate, Ovarian, NET, Lymphoma, Bladder…..
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17 רעין להצלחהג - צוינותמל חויבותמ
Liquid Lithium Target - LiLiT
7Li(p,n)7Be Eth=1.880 MeV
Jet chamber
liquid lithium
beam
• The basis for most of the R&D at SARAF• Liquid target enables utilization of the SARAF high power beam
At SARAF Phase I:
At SARAF Phase II:
An upgrade of LiLiT will be used with a deuteron beam to produce faster neutrons and higher flux
M. Paul (HUJI)
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18 רעין להצלחהג - צוינותמל חויבותמ
Lithium jet circulatingMeasured velocity 7 m/s
Maximum e power density 2.0 MW/cm3 @ 4 m/s
S. Halfon et al. App. Rad. Isot. 2011, INS26 2012, CARRI 2012
18 mm
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19 רעין להצלחהג - צוינותמל חויבותמ
E-gun thermal deposition tests
60 mA, 26 keV (~1.5 kW), σ=2.8 mm electrons in lithium (CASINO)
E-gun tests: High intensity – 26 keV, ~60 mAelectron gun emulate the power deposition peak of SARAF 1.91 MeV proton beam- up to 3 mA.
kW/cm3
[cm]
Dep
t in
Litiu
m[u
m]
-1 -0.5 0 0.5 1
0
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[cm]
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t in
Litiu
m[u
m]
-1 -0.5 0 0.5 1
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135
140
145
150
155
160
165 0
100
200
300
400
500
600
1 mA, 1.91 MeV (2 kW), σ=2.8 mm protons in lithium (TRIM)
kW/cm3
1 mA, 1.91 MeV, σ=2.8 mm protons in lithium (Bragg peak area)
[cm]
Dep
th in
lith
ium
[um
]
-1 -0.5 0 0.5 1
0
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kW/cm3
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20 רעין להצלחהג - צוינותמל חויבותמ
E-gun experiments resultsElectron beam power and vacuum in target chamber:
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21 רעין להצלחהג - צוינותמל חויבותמ
LiLiT installation at SARAF
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22 רעין להצלחהג - צוינותמל חויבותמ
LiLiT installation at SARAF
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23 רעין להצלחהג - צוינותמל חויבותמ
Boron Neutron Capture Therapy (BNCT)
1. Selectively deliver 10B to the tumor cells
2. Irradiate the target region with neutrons
3. The short range of the 10B(n,a)7Li reaction product, 5-8 mm in tissue, restrict the dose to the boron loaded area
n
n
n
n
n
Li
B10
B10
B10B1
0
B1
0B10
B10 B10
B10 B10
B10
B10
B10
~ 109 10B atoms in cell
α
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24 רעין להצלחהג - צוינותמל חויבותמ
10-2
100
102
104
106
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
Accelerator-based BNCT
O.E. Kononov et. al., Atomic energy, 94 (2003) 6
E. Bisceglie et al. Phys Med. Biol. 45 (2000) 49
Neutron flux: Optimal ≈109 s-1 cm-2 on beam port ** (for ~1 hour therapy)
SARAF lithium target >1010 s-1 mA-1
– Neutrons spectrum from lithium target bombarded with 1.91 MeV proton
S. Halfon et al. ICNCT 2008S. Halfon et. al., Appl Radiat Isot. 2009 Paul et al. US patent WO/2009/007976S. Halfon et al., App. Rad. Isot. 2011S. Halfon et al. INS26 2012 I. Silverman et al. CARRI 2012S. Halfon et al. ICNCT 2012
1. Produces the most suitable neutron spectrum for therapy
2. Accelerator free of residual activity3. Small – can be installed in hospital4. Good public acceptability5. Relatively low cost
M. Paul (HUJI)
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25 רעין להצלחהג - צוינותמל חויבותמ
Low Energy Linac
Middle Energy Linac
Linac/ Cyclotron
Accelerators
1.9-3 MeV 8-15 MeV 20- 30 MeV Energy (protons)
10-20 mA 5-10 mA 1-3 mA Average beam current
Lithium (solid or liquid)
Beryllium (solid) Beryllium (solid) Target
Up to1 MeV Up to15 MeV (peak at 1 MeV)
Up to 30 MeV (peak at 1 MeV)
Neutron energy at the target
Small Large Large Moderator and radiation shield size
High current linac, target
High current linac Almost nothing Technical obstacles
Feasibility study at SARAF phase I
Clinical system at SARAF phase II
Comparison of accelerators solutions
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26 רעין להצלחהג - צוינותמל חויבותמ
Comparison of neutrons flux densitySARAF
SPIRAL II *
IFMIF* Project
d(40MeV) +Li
d(40MeV) + C
d(40MeV) +Li
Reaction specification
19.1 4.3 19.1 Projectile range in target (mm)
5 5 2 x 125 Maximum beam current (mA)
~1 ~10 ~100 Beam spot on the target (cm2)
5 0.5 2.5 Beam density on the target (mA/cm2)
~0.07 ~0.03 ~0.07 Neutron production over 4π (n/deuteron)
~1015 ~1015 ~1017 Neutron source intensity (n/s)
~5∙1014 ~1014 ~1015Maximal neutron flux on the back-plate [n/(sec ∙ cm2)] (0-60 MeV neutrons)
~10 ~12 ~10 <En> on the back-plate (MeV)* D.Ridikas et.al. “Neutrons For Science (NFS) at SPIRAL-2 (Part I: material irradiations), Internal Report DSM/DAPNIA/SPhN, CEA Saclay (Dec 2003)
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27 רעין להצלחהג - צוינותמל חויבותמ
Simulation of stellar neutron spectrum for the study of nucleo-synthesis
G. Feinberg et al., PRC 2012, M. Freidman et al., NIM 2013
W. Ratynski and F. Kaeppeler, PR C (1988), Karlsruhe, I~50 mA
Principal shown at Karlsruhe at low current
• SARAF + LiLiT will enable study of rare processes with up to 3 mA (factor of 50 w.r.t Karlsruhe)
• N-capture of 90Sr is one of first reactions to be studied• RF beam produces a broad spectrum, more similar to Maxwellian
Measurement of S process cross sections
M. Paul (HUJI)
7Li(p,n)7Be Ep=1.912 MeV
s= 1 keVs= 15 keV
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28 רעין להצלחהג - צוינותמל חויבותמ
JRC-IAEC Collaboration to measure Neutron Induced Reactions
Important for Gen IV Reactor Development and Safety
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29 רעין להצלחהג - צוינותמל חויבותמ
Yield calculated for a 40 MeV, 1 mA deuteron beam
and for a ~ 800 cm3 cylindrical porous secondary target
For 6He, see ISOLDE Experiment, Stora et al., EPL, 98, 32001 (2012)
M. Hass (WIS)T. Hirsh (SNRC)
SARAF Production of light RIB Two-stage irradiation
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30 רעין להצלחהג - צוינותמל חויבותמ
6He b-decay in electrostatic trap
cos3
11)(
cos1
6
e
eSM
e
e
E
pHedW
E
padW
e+
ne
nucleus
q
e
e
p qaE E
- correlation
New physics beyond the Standard Model’s V-A structure
S. Vaintraub et al. J. of Physics 267 (2011)O. Aviv et al. J. of Physics 337 (2012)
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Acknowledgment Some of the research studies have been partially funded by
the Pazi foundation
Some of the research studies have been partially funded by the JRC-IAEA collaboration fund
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END