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Boron Neutron Capture Therapy Prof. Mauro Valente, PhD. Medical Physics – FaMAF CONICET & Universidad Nacional de.

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Presentation on theme: "Boron Neutron Capture Therapy Prof. Mauro Valente, PhD. Medical Physics – FaMAF CONICET & Universidad Nacional de."— Presentation transcript:

1 Boron Neutron Capture Therapy Prof. Mauro Valente, PhD. Medical Physics – FaMAF CONICET & Universidad Nacional de Cordoba ARGENTINA

2 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 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.

3 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: 1.The infusion or delivery of a capture compound, which preferentially concentrates in the tumor. 2.Then the irradiation of the tumor site by neutrons. As the isotope 10 B is often used as the neutron capture agent, in this case NCT is called Boron Neutron Capture Therapy (BNCT). Mauro Valente, PhD.

4 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 4 Boron Neutron Capture Therapy Exposure to thermal or epithermal neutrons 10 B (n,γ) 7 Li ( σ = 3837 barn) 10 B selectively accumulated in tumors Mauro Valente, PhD. n th 10 B 7 Li 

5 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 5 Why 10 B? The large cross section of thermal neutron interactions with 10 B isotope (σ th ~ 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.

6 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 6 BNCT – physical background Mauro Valente, PhD.

7 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 7 Therapy selectivity Mauro Valente, PhD.

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

9 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 9 Pathologies treated with BNCT Mauro Valente, PhD. 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

10 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 10 BNCT facilities around the world Mauro Valente, PhD. 07/05/ Algunos conceptos de Radiobiologia de BNCT RA-6 CNEA LBL U K Budker & IPPE Beijing LNL CNEA MIT Accelerators (under study) Pavia Reactors Japan Mainz

11 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 11 Treatment facility for BNCT Mauro Valente, PhD.

12 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 12 Treatment facility for BNCT: explanted liver Mauro Valente, PhD. 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

13 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 13 BNCT facility for explanted liver Mauro Valente, PhD.

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

15 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 15 BNCT Mauro Valente, PhD. 15 RADIOBIOLOGY The study and characterization of ionizing radiation effects on biological systems BNCT constitutes a mixed field radiation therapy modality, therefore:

16 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 16 BNCT Mauro Valente, PhD. 16 IONIZING RADIATION DIRECT IONIZING Charged particles, like electrons, protons, alpha particles, muons and heavy ions, which cause ionization by means of electromagnetic interactions and producing direct atom/molecule ionizations. The penetration capacity (range) is low.Charged particles, like electrons, protons, alpha particles, muons and heavy ions, which cause ionization by means of electromagnetic interactions and producing direct atom/molecule ionizations. The penetration capacity (range) is low. INDIRECT IONIZING Non charged particles, like photons and neutrons, which cause ionization by means of a two step mechanism consisting on a first excitation of charged particles and further ionizations and energy transfer to the irradiated media. The penetration capacity (mean free path) is high.Non charged particles, like photons and neutrons, which cause ionization by means of a two step mechanism consisting on a first excitation of charged particles and further ionizations and energy transfer to the irradiated media. The penetration capacity (mean free path) is high.

17 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 17 BNCT & equivalent dose Mauro Valente, PhD. 17 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.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).High LET radiation produces high ionization density per unit track, which significantly increases the biological effectiveness (lethal & sublethal radiation damage). Relative Biological Effectiveness (RBE)

18 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 18 High vs low LET radiation damage Mauro Valente, PhD. 18 High LETLow LET Direct damageIndirect damage

19 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 19 Temporal scale of radiation damage Mauro Valente, PhD. 19

20 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 20 Characteristics of nuclear reaction 10 B(n,α) 7 Li Mauro Valente, PhD. Particle type Energy (MeV) Range (μm) Mean LET (keV/μm) α Li What about X-rays? LET ( 60 Co) ~ 0.2 keV/μm & LET (250 keV) ~ 2 keV/μm

21 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 21 How to “deliver” 10 B to tumoral cells? Mauro Valente, PhD. 21 Different boron compound are commercially available as good candidate for carrier agents whitout contamination/biohazard risks for patient health: Na 2 B 12 H 11 SH 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 μg per g for BSH).

22 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 22 Typical radiation source characterization Mauro Valente, PhD. 22 Neutron beam typeSpectral range ThermalE n < 0.5 eV Epithermal0.5eV 10 keV

23 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 23 Typical radiation source characterization Mauro Valente, PhD. 23

24 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 24 Dosimetric properties of BNCT Mauro Valente, PhD. 24 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 [ 1 H(n,γ) 2 H].Low LET photons (γ rays) arrising mainly from neutron capture in H within the tissue [ 1 H(n,γ) 2 H]. High LET 1 H arrising from scattering of fast neutrons and neutron capture in N [ 14 N(n,p) 14 C].High LET 1 H arrising from scattering of fast neutrons and neutron capture in N [ 14 N(n,p) 14 C]. High LET 4 He particles nd 7 Li ions resulting from the neutron.induced fission reaction [ 10 B (n,α ) 7 Li].High LET 4 He particles nd 7 Li ions resulting from the neutron.induced fission reaction [ 10 B (n,α ) 7 Li].

25 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 25 Dosimetric properties of BNCT Mauro Valente, PhD H: n 0 capture in N Fast n 0 Total Dose Total γ dose 10 B dose (uniformly distributed)

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

27 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 27 Dosimetric properties of BNCT Mauro Valente, PhD. 27 … do you remember our initial goal-question? Is there any kind of treatment modality able to accomplish an “ideal” cancer cell control whereas no health tissue being affected? 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!!

28 Prof. Mauro Valente - CONICET & Universidad Nacional de Cordoba 28 Mauro Valente, PhD. 28 Boron Neutron Capture Therapy Prof. Mauro Valente, PhD. Medical Physics – FaMAF CONICET & Universidad Nacional de Cordoba ARGENTINA THANKS FOR YOUR KIND ATTENTION!!!


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