Evaluation of the near threshold 7 Li( p , n ) 7 Be accelerator-based irradiation system for BNCT

1. Evaluation of the near threshold 7Li(p,n)7Be accelerator-based irradiation system for BNCT A treatable protocol depth (TPD)-based characterization of neutron fields Gerard Bengua

2. Presentation Outline • Introduction • New protocol-based evaluation indices • Characterization of BDE Materials • TPD-based evaluation of near-threshold proton energies • Effects of variations in 7Li-target thickness • Gaussian proton beams for the near threshold 7Li(p,n)7Be reaction

3. Introduction

4. Introduction Boron Neutron Capture Therapy highly selective killing of tumor cells with simultaneous sparing of normal cells

5. Introduction Boron Compound that preferably delivers higher 10B concentration in tumor than in healthy cells Method for determining 10B concentration for accurate timing of neutron irradiation Success of BNCT Neutron irradiation field that can provide a high flux of thermal neutrons at sites where 10B accumulates

6. Introduction (Bayanov et al, 1998) Accelerator-based Neutron Sources (ABNS) can produce epithermal beam source with small fast neutron, thermal neutron and -ray contamination and feasible for a hospital-based BNCT Nuclear Reactors capable of producing high neutron flux with stable therapeutic properties for BNCT Radioisotopic source 252Cf Neutron sources for BNCT

7. Introduction • Accelerator-based neutron source for BNCT • Advantages: • Hospital-based implementation of BNCT • Familiarity of oncologist, medical physicist and technicians with accelerators in hospitals • Public acceptance

8. Introduction • Accelerator-based neutron source for BNCT • Candidate reactions for ABNS

9. Introduction • Accelerator-based neutron source for BNCT • Candidate reactions for ABNS • The 7Li(p,n)7Be reaction • Moderated neutron usage – Ep ~ 2.5MeV • Near-threshold neutron production • lower ave. neutron energy = no need for dedicated moderators • neutrons are kinematically collimated • more compact irradiation system Threshold energy: 1.881MeV

10. Introduction • Accelerator-based neutron source for BNCT • Candidate reactions for ABNS • The 7Li(p,n)7Be reaction • Moderated neutron usage – Ep ~ 2.5MeV • Near-threshold neutron production • feasibility for BNCT irradiation demonstrated by Tanaka et al (2002)

11. Introduction • Accelerator-based neutron source for BNCT • Candidate reactions for ABNS • The 7Li(p,n)7Be reaction • Recent research output of our group • Proposed new and more comprehensive dose evaluation indicesfor BNCT based on actual dose protocol; • Established a method for the characterization of neutron fields for BNCT; • Evaluated the various components of the near-threshold 7Li(p,n)7Be-ABNS for BNCT using the  and ;

12. New Protocol-based Evaluation Indices

13. Background and Definitions Treatable Region: (1) the tumor dose from HCP is greater than or equal to the treatment protocol dose for tumors; (2) the dose to healthy tissue do not exceed the tissue tolerance dose from either HCP or gamma rays set by protocol; Dose components of the intra-operative BNCT for brain tumor(Nakagawa et al., 2003) TheTreatable Protocol Depth (TPD)is the maximum depth of the treatable region relative to the surface facing the incident neutron beam. For symmetric geometries, this is located at the central axis.

14. BNCT dose components

15. Normalized dose components based on dose protocol The Treatable Protocol Depth (TPD) is equal to whichever is shallower between PD(hcp) and PD(). BNCT dose components

16. 38 ( Unit : mm ) BDE* H2O Phantom (180diam×200) 38 ( Unit : mm ) Proton Central axis BDE* H2O Phantom (180diam×200) 38 ( Unit : mm ) Proton Central axis H2O Phantom (180diam×200) Proton Central axis TPD = 2.11 cm TPD = 2.91 cm *BDE – Boron dose enhancer TPD = 0.45 cm

17. The relationship between BDE thickness and PD(hcp), PD() and TPD.

18. The relationship between BDE thickness and PD(hcp), PD() and TPD. TPDmax peak of the TPD versus BDE thickness curve BDE(TPDmax) the BDE thickness corresponding to TPDmax

19. Characterization of BDE materials

20. Objective • To determine possible optimization criteria for selecting appropriate BDE materials for BNCT. • In particular, • Evaluate the effects of various candidate BDE materials on the BNCT dose components; • 2. Examine the characteristics of candidate BDE materials in relation to the Treatable Protocol Depth (TPD) and other pertinent figures of merit;

21. Calculation Parameters Incident proton energy: 1.900MeV (mono-energetic) 7Li-target thickness: 2.33m BDE diameter: 18cm BDE thickness: Variable (chosen in order to attain the TPDmax for each BDE material) BDE material: Variable

22. Calculation Method Flowchart of Calculation Procedures Neutron production -ray production Particle transport Dose calculation Evaluation of dose distribution

23. Calculation Method Flowchart of Calculation Procedures Neutron production at the 7Li-target • Lee et al.’s code: calculation of neutron yields from thin 7Li-targetfor the near threshold 7Li(p,n)7Be reaction • Bethe’s stopping power formula: derivation of 7Li-target thickness Neutron production -ray production Particle transport Dose calculation Evaluation of dose distribution

24. Calculation Method Flowchart of Calculation Procedures Production of gamma-rays from proton-induced reactions Neutron production -ray production Particle transport Dose calculation Evaluation of dose distribution *Neutron induced production of gamma-rays are included in the MCNP simulation

25. Calculation Method Flowchart of Calculation Procedures Neutron and gamma-ray transport in the irradiation system Neutron production -ray production • Monte-carlo n-particle (MCNP) transport code (MCNP4C2, MCNPX) • Particle tally: neutron and gamma-ray flux • Estimated relative error of calculated data < 5% • S(,) thermal neutron scattering tables Particle transport Dose calculation Evaluation of dose distribution

26. Calculation Method Flowchart of Calculation Procedures Calculation of absorbed dose in tumor and healthy tissue Neutron production -ray production • Absorbed dose = flux * KERMA factor • Tissue composition: H(11.1), C(12.7), N(2.0), O(74.2) Particle transport Dose calculation Evaluation of dose distribution

27. Calculation Method Flowchart of Calculation Procedures Evaluation of dose distribution Evaluation indices: Treatable protocol depth (TPD), Heavy-charged particle protocol depth (PD(hcp)), Gamma-ray protocol depth (PD()) Applied dose protocol: Intra-operative BNCT dose protocol for brain tumors Neutron production -ray production Particle transport Dose calculation Evaluation of dose distribution

28. Dependence of PD(), PD(hcp) and TPD on BDE thickness Materials with (C2X4)n structure

29. Dependence of PD(), PD(hcp) and TPD on BDE thickness Materials with(C2HxFy)nstructure

30. Dependence of PD(), PD(hcp) and TPD on BDE thickness Materialswithout hydrogen

31. TPDmax, BDE(TPDmax) and Tumor dose rate at TPDmax forthe candidate BDE materials evaluated in this study

32. Summary • The following parameters together with other practical considerations may be used for choosing suitable BDE materials for BNCT: • TPDmaxdeeper is better for deep-seated tumors • BDE(TPDmax)thinner is better from the view point of dose rate reduction and material handling • TPD versus BDE thickness curvesmaller dependence of TPD on BDE thickness is better to avoid large variations in TPD for small changes in BDE thickness

33. TPD-based evaluation of near threshold proton energies for the 7Li(p,n)7Be production of neutrons for BNCT

34. Objective To evaluate the characteristics of neutron fields from the 7Li(p,n)7Be reaction at near-threshold incident proton energies with the treatable protocol depth (TPD) as the primary index of evaluation

35. Background Incident Proton Energy: 1.885 MeV Incident Proton Energy: 1.900 MeV

36. Background Incident Proton Energy: 1.885 MeV Incident Proton Energy: 1.900 MeV

37. Background Higher dose rate for all BNCT dose components Higher proton energy More effective for treatment Incident Proton Energy: 1.885 MeV Incident Proton Energy: 1.900 MeV

38. Calculation Method Simulation parameters

39. PD(hcp) and PD() curves generated by near-threshold proton energies

40. TPD curves generated by near-threshold proton energies

41. Higher proton energy  Higher ave.neutron energy  Lower relative difference between dose to tumor and to healthy tissue TPD curves generated by near-threshold proton energies The Colored arrows indicate the TPDmax

42. TPDmax, BDE(TPDmax), HCP dose rate at TPDmax and the required proton current to deliver 15 Gy per hour at TPDmax

43. Central axis distribution of HCP dose rate to tumor Colored region indicates the depths within the treatable region Gray-shaded region indicates the depths beyond the treatable region

44. Central axis distribution of HCP dose rate to tumor As an example, consider a tumor located at 3cm. The choice of the suitable proton energy will depend on the desired HCP dose rate to tumor.

45. Summary

46. Variation in 7Li-target thickness for near threshold 7Li(p,n)7Be neutron production for BNCT

47. To investigate the range of allowable 7Li-target thickness in the production of neutrons for BNCT via the near-threshold 7Li(p,n)7Be reaction Objective

48. Background • 7Li-target thickness for near-threshold neutron production at 1.900MeV  tmin = 2.33 m; minimizes gamma production in 7Li-target • Thicker 7Li-targets may be needed to extend target life-time if solid targets are used. • Thicker targets = larger gamma ray component in neutron field

49. Gamma ray yield for the proton-induced reactions in the 7Li-target and aluminum backing material. tmin=2.33m

50. Calculation Method Simulation parameters