1 1 מ חויבות ל מ צוינות - ג רעין להצלחה BNCT and other studies at Soreq EuCARD2 kickoff meeting Ido Silverman for SARAF team 14/6/2013

2 2 מ חויבות ל מ צוינות - ג רעין להצלחה SARAF Goals  To 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

3 3 מ חויבות ל מ צוינות - ג רעין להצלחה 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)

4 4 מ חויבות ל מ צוינות - ג רעין להצלחה 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

5 5 מ חויבות ל מ צוינות - ג רעין להצלחה ParameterValueComment Ion SpeciesProtons/DeuteronsM/q ≤ 2 Energy Range5 – 40 MeVVariable energy Current Range0.04 – 5 mACW (and pulsed) Operation6000 hours/year Reliability90% MaintenanceHands-OnVery low beam loss Phase I Phase II SARAF Accelerator Complex

6 6 מ חויבות ל מ צוינות - ג רעין להצלחה A. Nagler, Linac2006 K. Dunkel, PAC 2007 C. Piel, PAC 2007 C. Piel, EPAC 2008 A. Nagler, Linac 2008 J. Rodnizki, EPAC 2008 J. Rodnizki, HB 2008 I. Mardor, PAC 2009 A. Perry, SRF 2009 I. Mardor, SRF 2009 L. Weissman, DIPAC 2009 L. Weissman, Linac 2010 J. Rodnizki, Linac 2010 D. Berkovits, Linac 2012 L. Weissman, RuPAC 2012 SARAF phase-I linac - upstream view SARAF phase-I linac – upstream view

7 7 מ חויבות ל מ צוינות - ג רעין להצלחה EIS LEBT RFQ PSM MEBT Phase I D-plate Beam line targets Beam dumps SARAF Q  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

8 8 מ חויבות ל מ צוינות - ג רעין להצלחה SARAF applications  Thermal neutrons source for radiography and diffraction  Radio-isotopes production laboratory  Fast neutron source  aBNCT  Radiation damage studies  Basic physics research with radioactive beams

9 9 מ חויבות ל מ צוינות - ג רעין להצלחה Thermal neutron source TNR Diffractometer Thermal neutron source 9 Be(d,xn) beam 6 m Thermal Neutron Radiography (TNR) 2 mA deuteron 40 MeV 100 cm 2 Beryllium target 10 6 n/s/cm 2 on the detector

10 מ חויבות ל מ צוינות - ג רעין להצלחה 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,  ) 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)

11 מ חויבות ל מ צוינות - ג רעין להצלחה RadioisotopesMedical Use 64 Cu (β + ) 89 Zr (β + ) 111 In (γ) 124 I (β + )Diagnostics 68 Ge ( 68 Ga – β + ) 99 Mo ( 99m Tc – γ) Diagnostics Generator 67 Cu ( β - ) 103 Pd (X-rays) 177 Lu ( β - ) 186 Re ( β - ) 211 At ( α) 225 Ac ( α) Therapy Currently Preferred Options

12 מ חויבות ל מ צוינות - ג רעין להצלחה Production of 68 Ge. S. Halfon et al. AccApp11 conference (2011) 69 Ga(p,2n) 68 Ge Physical properties  Half-life = 68 min  Positron branching 89% (PET nuclide)  Available via 68 Ge/ 68 Ga generator  Parent 68 Ge cyclotron produced (T ½ = 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,…)

13 מ חויבות ל מ צוינות - ג רעין להצלחה Lutetium-177 Application of Lutetium-177  Currently, produced in reactors via 176 Lu (n,  ) 177 Lu;  Use for therapy with ability to employ dosimetry;  Labeling: peptides, proteins and antibodies. Physical properties  Half-life = 6.7 days  E  - = 490 keV / E  = 113 keV (3%), 210 keV (11%) Targe Linker SST 177 Lu

14 מ חויבות ל מ צוינות - ג רעין להצלחה *Hermanne A., et al, Int. Conf. on Nuc. Data for Science and Tec (2007 ) Activity (EOB)Irritation TimeCurrent / fluxTarget TypeFacility 3000 Ci/gr7 d3*10 13 n/cm 2 sEnriched Lu-176Reactor 222 Ci200 h5 mAEnriched Yb-176SARAF 28 Ci200 h5 mANatural YbSARAF Production of 177 Lu in SARAF  Via 176 Yb(d,x) 177 Lu (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;

15 מ חויבות ל מ צוינות - ג רעין להצלחה 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  -particles is negligible and does not depend on the cell cycle status.

16 מ חויבות ל מ צוינות - ג רעין להצלחה 225 Ac – Advantages  225 Ac: T ½ = 10 days; 213 Bi: T ½ = 46 min;  4  -emission at each decay (6 MeV) – high efficiency;  Ability to employ dosimetry;  Can be produced by SARAF at high yields.  225 Ac: clinical trials phase I : AML;  213 Bi: clinical trials phase I : AML, malignant, melanoma, Non- Hodgkin's lymphoma, NET;  225 Ac & 213 Bi: preclinical trials: Neuroblastoma, Breast, Prostate, Ovarian, NET, Lymphoma, Bladder…..

17 מ חויבות ל מ צוינות - ג רעין להצלחה Liquid Lithium Target - LiLiT 7 Li(p,n) 7 Be E th =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)

18 מ חויבות ל מ צוינות - ג רעין להצלחה Lithium jet circulating Measured velocity 7 m/s Maximum e power density 2.0 MW/cm 4 m/s S. Halfon et al. App. Rad. Isot. 2011, INS , CARRI mm

19 מ חויבות ל מ צוינות - ג רעין להצלחה 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 mA electron gun emulate the power deposition peak of SARAF 1.91 MeV proton beam- up to 3 mA. kW/cm 3 1 mA, 1.91 MeV (2 kW), σ=2.8 mm protons in lithium (TRIM) kW/cm 3 1 mA, 1.91 MeV, σ=2.8 mm protons in lithium (Bragg peak area) kW/cm 3

20 מ חויבות ל מ צוינות - ג רעין להצלחה E-gun experiments results Electron beam power and vacuum in target chamber:

21 מ חויבות ל מ צוינות - ג רעין להצלחה LiLiT installation at SARAF

22 מ חויבות ל מ צוינות - ג רעין להצלחה LiLiT installation at SARAF

23 מ חויבות ל מ צוינות - ג רעין להצלחה Boron Neutron Capture Therapy (BNCT) 1. Selectively deliver 10 B to the tumor cells 2. Irradiate the target region with neutrons 3. The short range of the 10 B(n,  ) 7 Li reaction product, 5-8  m in tissue, restrict the dose to the boron loaded area n n n n n Li B 10 ~ B atoms in cell α

24 מ חויבות ל מ צוינות - ג רעין להצלחה 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 ≈10 9 s -1 cm -2 on beam port ** (for ~1 hour therapy) SARAF lithium target >10 10 s -1 mA -1 – Neutrons spectrum from lithium target bombarded with 1.91 MeV proton S. Halfon et al. ICNCT 2008 S. Halfon et. al., Appl Radiat Isot Paul et al. US patent WO/2009/ S. Halfon et al., App. Rad. Isot S. Halfon et al. INS I. Silverman et al. CARRI 2012 S. Halfon et al. ICNCT Produces the most suitable neutron spectrum for therapy 2.Accelerator free of residual activity 3.Small – can be installed in hospital 4.Good public acceptability 5.Relatively low cost M. Paul (HUJI)

25 מ חויבות ל מ צוינות - ג רעין להצלחה Low Energy Linac Middle Energy Linac Linac/ Cyclotron Accelerators MeV8-15 MeV MeVEnergy (protons) mA5-10 mA1-3 mAAverage beam current Lithium (solid or liquid) Beryllium (solid) Target Up to1 MeVUp to15 MeV (peak at 1 MeV) Up to 30 MeV (peak at 1 MeV) Neutron energy at the target SmallLarge Moderator and radiation shield size High current linac, target High current linacAlmost nothingTechnical obstacles Feasibility study at SARAF phase I Clinical system at SARAF phase II Comparison of accelerators solutions

26 מ חויבות ל מ צוינות - ג רעין להצלחה Comparison of neutrons flux density SARAFSPIRAL II *IFMIF *Project d(40MeV) +Lid(40MeV) + Cd(40MeV) +Li Reaction specification Projectile range in target (mm) 552 x 125 Maximum beam current (mA) ~1~10~100 Beam spot on the target (cm 2 ) Beam density on the target (mA/cm 2 ) ~0.07~0.03~0.07 Neutron production over 4π (n/deuteron) ~10 15 ~10 17 Neutron source intensity (n/s) ~5∙10 14 ~10 14 ~10 15 Maximal neutron flux on the back-plate [n/(sec ∙ cm 2 )] (0-60 MeV neutrons) ~10~12~10 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)

27 מ חויבות ל מ צוינות - ג רעין להצלחה 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  A 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 90 Sr 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) 7 Li(p,n) 7 Be E p =1.912 MeV  = 1 keV  = 15 keV

28 מ חויבות ל מ צוינות - ג רעין להצלחה JRC-IAEC Collaboration to measure Neutron Induced Reactions Important for Gen IV Reactor Development and Safety

29 מ חויבות ל מ צוינות - ג רעין להצלחה Yield calculated for a 40 MeV, 1 mA deuteron beam and for a ~ 800 cm 3 cylindrical porous secondary target For 6 He, see ISOLDE Experiment, Stora et al., EPL, 98, (2012) M. Hass (WIS) T. Hirsh (SNRC) SARAF Production of light RIB Two-stage irradiation

30 מ חויבות ל מ צוינות - ג רעין להצלחה 6 He  -decay in electrostatic trap e+e+ e nucleus   - 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)

31 מ חויבות ל מ צוינות - ג רעין להצלחה 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

32 מ חויבות ל מ צוינות - ג רעין להצלחה END

33 מ חויבות ל מ צוינות - ג רעין להצלחה Target vacuum chamber Lithium containment tank, heat exchanger and Be-7 cold trap EM pump loop SARAF Proton Beam LiLiT- Liquid Lithium Target Lithium nozzle (neutron port) Flow-meter S. Halfon et al., Applied Radiation and Isotopes (2011).

34 מ חויבות ל מ צוינות - ג רעין להצלחה Target vacuum chamber Beam Direction Lithium flow Vapor trap Proton beam Lithium nozzle Diagnostic port View port

35 מ חויבות ל מ צוינות - ג רעין להצלחה proton beam liquid lithium flow Emitted neutrons Stainless Steel walls Lithium Nozzle Lithium flow Proton beam Curved thin back-wall Nozzle "ears" Proton beam Lithium flow: 18 mm wide 1.5 mm thick 1 cm