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Boron Neutron Capture Therapy

Boron Neutron Capture Therapy. Prof. Mauro Valente, PhD. Medical Physics – FaMAF http://www.famaf.unc.edu.ar/~valente/. CONICET & Universidad Nacional de Cordoba ARGENTINA. The GOAL.

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Boron Neutron Capture Therapy

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  1. Boron Neutron Capture Therapy Prof. Mauro Valente, PhD. Medical Physics – FaMAF http://www.famaf.unc.edu.ar/~valente/ CONICET & Universidad Nacional de Cordoba ARGENTINA

  2. The GOAL It is well known that radiation therapies tray to assess tumor control by means of killing cancer cells while sparing health tissues. Therefore, is there any kind of treatment modality able to accomplish an “ideal” cancer cell control whereas no health tissue being affected? HINT: Radiation damage selectivity Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  3. What is BNCT? Today Neutron Capture Therapy (NCT) is a promising form of radiation therapy, which includes 2 interconnected features: • The infusion or delivery of a capture compound, which preferentially concentrates in the tumor. • Then the irradiation of the tumor site by neutrons. As the isotope 10B is often used as the neutron capture agent, in this case NCT is called Boron Neutron Capture Therapy (BNCT). Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  4. Li 7 n B 10 th a Boron Neutron Capture Therapy • Exposure to thermal or epithermal neutrons • 10B (n,γ) 7Li ( σ= 3837 barn) • 10B selectively accumulated in tumors Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  5. Why 10B? • The large cross section of thermal neutron interactions with 10B isotope (σth~ 4 000 barn) causes high probability of a slitting of boron nucleus onto He and Li. • As ionization capability of He and Li ions is high, and their runs (range) are short, then the cells, preferably enriched by boron, are killed and the healthy cells are damaged much less. Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  6. BNCT – physical background Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  7. Therapy selectivity Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  8. Within patient’s body fast neutrons epithermal neutrons slow neutrons Cell-killing 10B-Capture in Tumor Neutron sources Moderator Material Tissue (moderator) Neutron Sources • Epithermal neutron (0.4 eV - 10 keV) beams are availablefrom existing nuclear reactors. Charged-particle accelerators, compact neutron generators and hospital radiotherapy facilities for BNCT (PHONES - INFN)arenow under development. • Epithermal neutrons lose energy in the patient body and become capturable slow (thermalized) neutrons while proceeding to the tumour. Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  9. Pathologies treated with BNCT • Brain tumor (epithermal) • Fir-1 Espoo Helsinki, Finland • Massachusetts Institute of Technology • Brookhaven National Laboratory; • RA-6 Reactor at the Bariloche Atomic Center Buenos Aires, Argentina • Studsvik, Sweden • High Flux Reactor Petten, Netherlands • H&N tumor (epithermal) • Kyoto University Reasearch Reactor, Japan • Melanoma (thermal) • Massachusetts Institute of Technology • RA-6 Reactor at the Bariloche Atomic Center Buenos Aires, Argentina • Explanted Liver(thermal) • Triga Mark II reactor Pavia, Italy Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  10. MIT Accelerators (under study) BNCT facilities around the world U K Japan Budker & IPPE Mainz LBL Japan LNL Pavia Beijing CNEA RA-6 CNEA Reactors Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Algunos conceptos de Radiobiologia de BNCT Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 10 01/09/2014

  11. Treatment facility for BNCT Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  12. Treatment facility for BNCT: explanted liver Spheroidal Holder for Liver Treatment at the HFR (Petten) Liver holder placed in PMMA block Block and holder placed in graphite cage Beam-eye view of final configuration, covered with polyethylene sheet Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  13. BNCT facility for explanted liver Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  14. BNCT main features Neutron reactions in tissue without 10B: Thermal Neutrons: 1H(n,)2H  = 0.33 b E = 2.2 MeV 14N(n,p)14C = 1.9 b E(p) = 0.63 MeV Epithermal and fast neutrons: elastic scattering pmainly with H (backscattering p+) Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  15. BNCT BNCT constitutes a mixed field radiation therapy modality, therefore: RADIOBIOLOGY The study and characterization of ionizing radiation effects on biological systems Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 15

  16. BNCT IONIZING RADIATION • DIRECT IONIZING • Chargedparticles, likeelectrons, protons, alphaparticles, muons and heavy ions, which cause ionizationbymeans of electromagneticinteractions and producingdirectatom/moleculeionizations. Thepenetrationcapacity (range) islow. • INDIRECT IONIZING • Non chargedparticles, likephotons and neutrons, which cause ionizationbymeans of a twostepmechanismconsistingon a firstexcitation of chargedparticles and furtherionizations and energy transfer totheirradiated media. Thepenetrationcapacity (mean free path) ishigh. Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 16

  17. BNCT & equivalent dose Mixed field modality • LINEAR ENERGY TRANSFER (LET) • Low LET radiations, like photons, induce only a little quantity of ionizations along the track while traveling within the irradiated material. • High LET radiation produces high ionization density per unit track, which significantly increases the biological effectiveness (lethal & sublethal radiation damage). Relative Biological Effectiveness (RBE) Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 17

  18. High vs low LET radiation damage Direct damage Indirect damage High LET Low LET Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 18

  19. Temporal scale of radiation damage Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 19

  20. Characteristics of nuclear reaction 10B(n,α)7Li ... What about X-rays? LET (60Co) ~ 0.2 keV/μm & LET (250 keV) ~ 2 keV/μm Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba

  21. How to “deliver” 10B to tumoral cells? Different boron compound are commercially available as good candidate for carrier agents whitout contamination/biohazard risks for patient health: • Na2B12H11SH mercaptoundecahydrododecaborate (BSH) • Boronophenylalanine (BPA) • Both of them have proved to be non dangerous for patient treatment within the • administration range (12-90 μg per g for BPA and 20-120 μg per g for BSH). Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 21

  22. Typical radiation source characterization Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 22

  23. Typical radiation source characterization Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 23

  24. Dosimetric properties of BNCT • Radiation field on tissue during BNCT irradiation is constituted by 3 main contributions of significant different LET and therefore different RBE: • Low LET photons (γ rays) arrising mainly from neutron capture in H within the tissue [1H(n,γ)2H]. • High LET 1H arrising from scattering of fast neutrons and neutron capture in N [14N(n,p)14C]. • High LET 4He particles nd 7Li ions resulting from the neutron.induced fission reaction [10B (n,α ) 7Li]. Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 24

  25. Total Dose Fast n0 Total γdose 10B dose (uniformly distributed) 1H: n0 capture in N Dosimetric properties of BNCT Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 25

  26. Fast neutrons Photons Thermal neutrons Boron ( and 7Li) Electrons Total TOTAL PHOTONS AUGER ELECTRONS FAST NEUTRONS TUMOR Dosimetric properties of BNCT Dose-rates in the central axis of a phantom containing 10 ppm of 10B and a simulated tumor with 35 ppm of 10B Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 26

  27. Is there any kind of treatment modality able to accomplish an “ideal” cancer cell control whereas no health tissue being affected? Dosimetric properties of BNCT … do you remember our initial goal-question? BNCT seems to be an excellent candidate … but, what kind of “magic” dosimetric method may be able for 3D dose contribution quantification in the mixed BNCT field? I hope to offer you an answer in the next talk!! Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 27

  28. Boron Neutron Capture Therapy Prof. Mauro Valente, PhD. Medical Physics – FaMAF http://www.famaf.unc.edu.ar/~valente/ CONICET & Universidad Nacional de Cordoba ARGENTINA THANKS FOR YOUR KIND ATTENTION!!! Mauro Valente, PhD. http://www.famaf.unc.edu.ar/~valente/ Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 28

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