1 1 מ חויבות ל מ צוינות - ג רעין להצלחה BNCT and other studies at Soreq...

1 רעין להצלחהג - צוינותמל חויבותמ

BNCT and other studies at Soreq

EuCARD2 kickoff meeting

Ido Silverman for SARAF team

14/6/2013


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


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)


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


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


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


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


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


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


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)


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


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,…)


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


*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;


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.


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…..


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)


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


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

20

40

60

80

100

120

140

1600

100

200

300

400

500

600

[cm]

Dep

t in

Litiu

m[u

m]

-1 -0.5 0 0.5 1

130

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

5

10

15

20

25

30

35

40

0

200

400

600

800

1000

1200

1400

1600

1800

kW/cm3


E-gun experiments resultsElectron beam power and vacuum in target chamber:


LiLiT installation at SARAF


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


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)


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


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)


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


JRC-IAEC Collaboration to measure Neutron Induced Reactions

Important for Gen IV Reactor Development and Safety


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


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)


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


END

1 1 מ חויבות ל מ צוינות - ג רעין להצלחה BNCT and other studies at Soreq...

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