Accelerator-based versus Reactor-based neutron sources for BNCT – an ISNCT perspective Ray Moss (Secretary/Treasurer ISNCT) Sector Leader Medical Applications, High Flux Reactor Unit, Institute for Energy, Joint Research Centre, Petten, The Netherlands
Contents ISNCT BNCT History Status Reactors or Accelerators? Future of BNCT
ISNCT ISNCT CONSTITUTION Article I NAME OF SOCIETY The organization shall be called The International Society for Neutron Capture Therapy . Article II PURPOSE OF SOCIETY The purpose of the Society shall be to promote widespread interest in neutron capture therapy and related forms of management of cancer and other diseases with present emphasis on neutron capture therapy. This promotion includes the holding of scientific meetings and other such endeavors as seen appropriate to the Executive Board.
1st 12-14 October 1983 Cambridge, MA, USA Brownell/Fairchild 2nd 18 - 20 October 1985 Tokyo,Japan Hiroshi Hatanaka 3rd 31 May - 3 June 1988 Bremen, Germany Detlef Gabel 4th 4-7 December 1990 Sydney, Australia Barry J. Allen 5th 14-17 September 1992 Columbus, OH, USA Albert J. Soloway 6th 31 October - 4 November 1994 Kobe, Japan Yutaka Mishima 7th 4-7 September 1996 Zurich, Switzerland Börje Larsson 8th 13-18 September 1998 La Jolla, CA, USA Fred Hawthorne 9th 2 – 6 October 2000 Osaka, Japan Keiji Kanda 10th 8- 13 September 2002 Essen, Germany W. Sauerwein 11th 11-15 October 2004 Boston, USA Robert Zamenhof 12th 9-13 October 2006 Takamatsu, Japan Yoshi Nakagawa 13th 2-7 November 2008 Florence, Italy Aris Zonta Biennial Congresses on NCT
Committee for Standards in Dosimetry Committee for Standards & Protocols in Clinical Trials Committee for Standards in Treatment Planning Committee for Financial Auditing Committee for Standards in Accelerators Committees on NCT
BNCT is based on the ability of the isotope 10 B to capture low energy neutrons to produce two highly energetic particles with low range in tissue. What is BNCT ? Boron Neutron Capture Therapy gamma 0.48 MeV 10 B 0.84 MeV 7 Li 1.47 MeV 4 He(alpha) n th
<ul><li>Success of BNCT requires : </li></ul><ul><li>a large number of 10 B atoms must be </li></ul><ul><li>localised selectively within the tumour </li></ul><ul><li>cells </li></ul><ul><li>a sufficient number of thermal neutrons </li></ul><ul><li>must reach and be captured by 10 B </li></ul>
How to deliver thermal neutrons to the boronated tumour cells? <ul><li>Possible sources of neutrons, include: </li></ul><ul><li>Nuclear reactors </li></ul><ul><li>Accelerators </li></ul><ul><li>Radioisotopes (Cf 252) </li></ul><ul><li>Neutron Generators (D-D / D-T) </li></ul>E n » … MeV
Neutron Beams for BNCT Generation 3: Next wave of US trials (epithermal neutron beams):- 1. M.I.T.R.-II, 1994-1999  2. BMRR, 1994-1999  - In total, 71 patients Generation 1: Early US trials:- 1. Brookhaven Graphite Research Reactor (BGRR), 1951-61 * 2. Brookhaven Medical Research Reactor (BMRR), 1959-61  3. M.I.T. Reactor, 1959-61  - In total 63 patients <ul><li>Generation 2: Japanese Reactors: </li></ul><ul><li>1. Hitachi Training Reactor, 1968-75  </li></ul><ul><li>2. JRR-3 (JAERI), 1969  </li></ul><ul><li>3. JRR-4 (JAERI), 1990 … 1999  </li></ul><ul><li>4. Musashi I.T.R., 1977-89 [>100] </li></ul><ul><li>5. Kyoto Univ. Research Reactor (KURR), 1975, 1981, 1990… [>60] </li></ul><ul><li>6. JRR-2 (JAERI), 1990  </li></ul><ul><li>all above reactors use(d) thermal neutrons </li></ul><ul><li>In total, over 200 patients </li></ul>
Present Neutron Beams used in BNCT 2. JRR-4 (JAERI) 1998 [>10, glioma, meningioma] 3. KUR, Kyoto, Japan 1998 [>50 head and neck] 3. VTT, Finland 1999 [>100, now mainly head and neck] 4. Rez, Czech Rep. 2000 [5, glioblastoma] 5. Studsvik, Sweden 2001 [>40] 6. MIT, USA 2002  7. Pavia, Italy 2001 [2, extracorporeal liver] 8. Bariloche, Argentina 2003 [3, skin melanoma] 9. THOR, Taiwan 2008 10.HANORA, S. Korea 2008 Generation 4: new generation 1. HFR Petten 1997 [26-glioblastoma, 4-melanoma metastases] With imminent closure?? ALL using nuclear research reactors
Status ??? Recent results (ICNCT 2006) Both in Japan (Osaka University) and Finland (Helsinki), successful treatment of Head and Neck cancers. Finns also showed good results for recurrent glioblastoma. Argentina reported on the successful treatment of multinodular skin melanoma (3 patients). Japan reports on successful BNCT for Cutaneous and Mucosal melanoma. Japan (Tsukuba) results of a combined photon + BNCT study (glioblastoma), the outcome is very good. Other studies for the treatment of thyroid cancer, melanoma and head and neck cancers (all in Japan).
Which type of cancer? Energy of neutrons required??
Factors in beam design – Therapeutic gain - is defined as the ratio of the total dose in the tumour at depth to the maximum dose in the healthy tissue. epithermal neutrons utilise the overlying tissue to lose their energy, principally through elastic scatter with hydrogen nuclei, and become thermalised
“ SLOW” (THERMAL) NEUTRONS - low penetration in tissue - high reaction rate 10 B(n, ) 7 Li reaction “ FAST” (EPITHERMAL) NEUTRONS - high penetration in tissue - low reaction rate 10 B(n, ) 7 Li reaction Prague, 11-12 Nov 2005
Dose components in tissue, due to a reactor beam Neutron absorbed dose D n Gamma ray absorbed dose D g Nitrogen neutron capture absorbed dose D N Boron neutron capture absorbed dose D B
<ul><li>epithermal neutron flux 10 9 neutrons/cm 2 s </li></ul><ul><li>(at the therapy position) </li></ul><ul><li>neutron energy ~ 1 eV to ~ 10.0 keV </li></ul><ul><li>gamma dose rate 1.0 Gy/hr </li></ul><ul><li>fast neutron dose rate 0.5Gy/hr </li></ul><ul><li>current:flux (J/ ) ratio > 0.8 </li></ul>Neutron beam requirements - the parameter J/ reflects the forward directionality (degree of collimation) of the beam of neutrons, which equals 0.5 for a completely isotropic beam and 1.0 for a purely parallel beam
Present Reactor-based Neutron Beams for BNCT Japan Atomic Energy Research Institute, Tokai , Ibaraki, Japan HFR Petten, Netherlands MIT, Boston, USA
Examples of materials used in beam designs for BNCT at various reactors Reactors Moderators Filters Attenuators BMRR H 2 O, C Al, Cd, Al 2 O 3 Bi MITR-II H 2 O, D 2 O Al, S, Cd, Li Bi, poly- 6 Li HFR H 2 O Al, Ti, S, Cd Ar, poly-B fission plate Al 2 O 3 , Al, H 2 O Al, LiF 3 Bi, Pb, 6 Li Mu.ITR Al, C, H 2 O Al, LiF 3 Bi TRIGA C, H 2 O LiF 3 Bi, Pb R2-0 Al, H 2 O/D 2 O Al, Li, teflon Bi, Pb, 6 Li FiR I (TRIGA) Al Fluental Bi
Is there an optimal approach ? Many variables Reactor type Tumour to be treated, size, location, depth ……. Boron compound to be used .............. Use of a variable, dynamic filter arrangement, producing a shift in neutron energy spectrum, changing neutron intensity, a rotating beam or patient,…………. Theoretically – Yes But practically ….No BNCT facility to suit the type of tumour to be treated
<ul><li>2 cameras (one fixed, one moveable placed on a tripod close to the patient) </li></ul><ul><li>2-way intercom (communication with the observation area) </li></ul><ul><li>microphone (patient-to-medical staff) </li></ul><ul><li>4 electro-optical laser positioning devices </li></ul><ul><li>lighting (special non-reflecting shades) </li></ul><ul><li>wash-basin, with hot warm water </li></ul><ul><li>anti-static, low conducting floor covering </li></ul><ul><li>various electrical (earthed) sockets placed around the room </li></ul><ul><li>aluminium storage rack </li></ul><ul><li>aluminium therapy table, moveable in all </li></ul><ul><li>3 orthogonal directions (electrical motor </li></ul><ul><li>to move the table in the vertical direction </li></ul><ul><li>a stop/start button, to initiate the </li></ul><ul><li>procedure to start treatment </li></ul><ul><li>air conditioning </li></ul><ul><li>infra red sensors to detect presence of </li></ul><ul><li>unauthorised personnel (causes </li></ul><ul><li>closure of the beam shutters) </li></ul><ul><li>numerous micro-switches on main door </li></ul><ul><li>and labyrinth door to detect the open/ </li></ul><ul><li>close status of the doors </li></ul><ul><li>electrical interlock system. </li></ul>The irradiation room has been built to reflect as close as possible, and within reason, a hospital-type environment. As such, the following items have been installed :- The BNCT Facility at the HFR Petten
BNCT - HFR Petten The BNCT-Wing - arrival of patient
<ul><li>BNCT is: </li></ul><ul><li>complex </li></ul><ul><li>performed outside a hospital environment </li></ul><ul><li>performed in a nuclear reactor </li></ul><ul><li>Not CONVENTIONAL treatment </li></ul><ul><li>BNCT is: </li></ul><ul><li>multi-disciplinary </li></ul>Reactors have been and are still being used to treat patients by BNCT HFR Petten
Presentations at the last ICNCT 2006, Takamatsu, Japan Accelerator-based systems for BNCT IPPE, Korkachov, Russia Hanyang University, Seoul, South Korea Tohoku University, Japan IBA – dynamitron – Japan Hitachi – Japan CNEA, Argentina Budker INP, Novosibirsk, Russia KURR, Kyoto, Japan THE major problem is that nuclear reactors for BNCT use, are very unlikely to be built and located in a hospital – Accelerators already exist in hospitals!
The Medical Physics Building in Birmingham Cyclotron vault Dynamitron Protons Neutrons Li target, Beam moderator / shield
The actual treatment facility (mid 2003) Proton beam-tube Heavy water reservoir FLUENTAL TM moderator Li-polythene delimiter / shield Heavy water inlet To pumps / chiller Neutron source is > 1 x 10 12 s -1
In conclusion …… Reactor-based facilities have been used, and are still being used for BNCT, for over 50 years. Economical and logistical reasons – difficult to sustain Accelerator-based facilities are the future of BNCT BUT they must be able to demonstrate that the required beam characteristics can be achieved