2. BNCT, a binary radiotherapy at cellular level
Dr. César Ceballos Sánchez. (CEADEN)
Physics and Applications of High Brightness Beams
Havana, Cuba, March 28th - April 1st, 2016.

3. This story will be told backwards.

4. Boron Neutron Capture Therapy (...and they lived happily ever after.)

5. Boron Neutron Capture Therapy (BNCT)
a) 10B carrier, selectively uptaken in tumor cells
Binary Radiotherapy
b) Thermal neutrons beam ( En< 0.5 eV) at tumor zone n
Nuclei σc(nth)[barns]
10B 1H
12C
14N
16O
7Li
4He
10B
10B(n, 4He) 7Li*
7Li + γ (0.48 MeV) MeV
(94%)
10B(n, 4He) 7Li MeV
(6%)

6. Boron-delivery agents
- Boron in the tumor ~ ppm
- The tumor-to-normal tissue ratio > 3
- Low toxicity
Historically: sodium borocaptate (BSH)
p - Borono- phenylalanine (BPA)
Current development
boron delivery agents +
tumour- targeting molecules
(peptides, proteins, anti-bodies,
nucleosides, sugars, porphyrins and liposomes)
optimization of the administration method
(nanoscale drug delivery systems using
liposomes and nanoparticles)

7. Φn > 109 cm-2s-1 of "proper" neutron spectrum at patient's entrance
Therapeutic beam
Φn > 109 cm-2s-1 of "proper" neutron spectrum at patient's entrance
Thermal (En < 0.5 eV)
Shallow tumor: skin melanoma
Epithermal (0.5 eV < En < 10 KeV)
Deep-seated: brain tumor (GBM)
90%
Primary beam
BSA
Therapeutic beam
(Neutron fluency rate degradation
&
gamma rays production)

8. D = wBDB + wn,thDn,th + wn,f Dn,f + Dγ
Therapeutic beam
D = wBDB + wn,thDn,th + wn,f Dn,f + Dγ
10B(n,α)
14N(n,p)14C
1H(n,n’)1H
1H(n,γ)1H +
γ from BSA
Mixed radiation field

9. D = wBDB + wn,thDn,th + wn,f Dn,f + Dγ
Therapeutic beam
D = wBDB + wn,thDn,th + wn,f Dn,f + Dγ
ICRU-63, International Commission on Radiation Units and Measurements, 2000
Soft tissue
Soft tissue + 45 ppm 10B
Normalized neutron Kerma (Gy.cm-2.n-1)
Neutron Energy (MeV)
Mixed radiation field

10. Therapeutic beam It strongly depends on the primary beam
- High fluency rate at the "right" energy
- As little as possible “contaminants” in the radiation beam
- Directed into the tumor bed
It strongly depends on the primary beam

11. Neutron Source
(Once upon a time...)

12. Neutron Source
- All reported BNCT irradiations on patients have been performed at nuclear research reactors
MITR (USA)
VTT-FR1 (Finland)
THOR (Taiwan)
KURR, JRR-4 (Japan)
RA-6 (Argentina)
Nuclear Reactors: Source & Doom for BNCT
- High neutron intensity
- Very expensive facilities
- Limited number available for BNCT
- Far away from hospitals
- Safety regulations
- Increasingly unpopular
Particle accelerators: The shining knights
- Cheaper facilities
- Placed inside hospitals
- Electric machines
- Higher public acceptance
- Lower intensity

13. Accelerator-Based BNCT
(told forward)
Ion source
Proton beam
Reflector
RFQ accelerator
Moderator
Proton beam
Target
BNCT
(BSA) . .

14. Accelerator-Based BNCT Nuclear reaction candidates (...or 7Li vs 9Be)
7Li(p,n)7Be
Ep threshold = MeV
at Ep = 2.3 MeV
En,max= keV
9Be(p,n)9B
Ep threshold = 2.06 MeV
at Ep = 4 MeV
En,max= MeV
Lithium
Melting point: 180 oC
Thermal cond.: 85 W m-1 K-1
7Be => radioactive
Beryllium
Melting point: 1287 oC
Thermal cond.: 190 W m-1 K-1

15. Accelerator-Based BNCT Nuclear reaction candidates (...or 7Li vs 9Be)
Kreiner et al., Reports of Practical Oncology and Radiotherapy, 21 (2016)

16. Accelerator-Based BNCT
AB-BNCT Worldide
Kreiner et al., Reports of Practical Oncology and Radiotherapy, 21 (2016)

17. BNCT recent clinical trials
(RB-BNCT)
Finland:
(2008) Recurrent GBM:
- 22 patients previously undergone standard therapy and following recurrence, received
BNCT using BPA as the boron delivery agent
- Median Survival Time: 7 Months
(2011) Recurrent Head and Neck Cancer
- 30 patients with inoperable, locally recurrent cancers of the head and neck region
- The two-year overall survival was 30%
- 27% of the patients had no evidence of recurrent disease at 2 years.
Japan:
(2008) Recurrent Head and Neck Malignancies (HNM)
- 26 patients were treated with BNCT following recurrence of HNM after treatment with
standard therapy. It had been considered that there were no other treatment options
- BNCT was found to improve QOL
- Survival periods after BNCT ranged from 1 to 84 months
R L. Moss, Critical review, with an optimistic outlook, on BNCT, ARI, 88 (2014), 2-11

18. Final Remarks
- BNCT involves multidisciplinary collaboration from nuclear physics to surgery,
from chemistry to radiation oncology, and from mathematics to radiation biology.
- Clinical trials have shown good results on treating recurrent cancers as:
GBM, Head and Neck, Lung and Gastrointestinal.
- The advancement (and the future) of BNCT requires neutron sources suitable for
installation in hospital environments. Particle accelerators are most appropriate for
this purpose.

19. The End

22. In-air FOM for the therapeutic
beam.
Limits
Φn th(≤ 0.5 eV)
≥ 109 [cm-2 s-1]
Φn th/ Φn tot
≥ 0.90
Kn epi+fast / Φn th
≤ 2· 10-13[Gy cm2]
Kγ/ Φn th