Accelerator-Based Boron Neutron Capture Therapy Paolo Colautti, INFN - - PowerPoint PPT Presentation

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Accelerator-Based Boron Neutron Capture Therapy Paolo Colautti, INFN - - PowerPoint PPT Presentation

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IFMIF/ELAMAT Accelerator-Based Boron Neutron Capture Therapy Paolo Colautti, INFN Town meting on IFMIF/ELAMAT Rzeszw 14-15 April 2016 Talk Topics 1. BNCT rationale. 2. BNCT drawbacks. 3. BNCT medical results. 4. Neutron sources from

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IFMIF/ELAMAT

Accelerator-Based Boron Neutron Capture Therapy

Paolo Colautti, INFN

Town meting on IFMIF/ELAMAT Rzeszów 14-15 April 2016

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

Talk Topics

  • 1. BNCT rationale.
  • 2. BNCT drawbacks.
  • 3. BNCT medical results.
  • 4. Neutron sources from particle accelerators.
  • 5. The Neutron Beam-Shaping Assembly.
  • 6. Treatable tumours: the Advantage Depth.
  • 7. The AB-BNCT 4 pillars:
  • 1. powerful accelerator;
  • 2. safe target handling;
  • 3. tracing the Boron carrier;
  • 4. microdosimetric detector.
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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

Rationale: BNCT is a Cellular Hadronic Therapy

10B + n  11B  7Li + 4He + 2.8 MeV

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

BNCT Drawbacks: Nuclear Reactions Which Damage Also Health Cells

Reaction Q-Value (MeV) Cross Section barn Threshold MeV

1H(n, γ)2H

+2.22 20.8

  • 14N(n,p)14C

+0.63 1.6

  • 14N(n,α)11B
  • 0.158

0.084 0.17

40Ca(n,α)37Ar

+1.75 0.05

  • 16O(n,α)13C
  • 2.16

0.008 2.36

10B+n 7Li+4He

2.79 3837

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

BNCT Medical Results: Kaplan-Meier Plots

Head and Neck Cancer Glioblastoma

Nuclear Physics for Medicine. NuPECC Report, edit A.Bracco et al. 2014, http://www.nupecc.org/npmed/npmed2014_hires.pdf

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

Short Conclusion about BNCT Clinical Results

  • Treatments with thermal neutrons

(skin melanomas, explanted liver, brain-glioblastoma intraoperative irradiation) were successful.

  • Treatments with epithermal neutrons

are only partially successful.

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

Accelerator-Based BNCT (AB-BNCT)

  • So far, all BNCT treatments have used

nuclear research reactors.

  • Unlikely nuclear reactors could be installed

inside a hospital.

  • The use of a dedicated particle accelerator,

rather than a research reactor, will implement a real clinical BNCT.

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

Neutron Sources Exploitable for AB-BNCT

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The Beam Shaping Assembly to Slow Down and Shaping the Neutron Beam

Teflon container Gamma shield: Pb+Bi

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The LNL Beam-Shaping Assembly 5 MeV Proton beam Thermal-neutron beam port

Be target

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The Advantage Depth

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The AB-BNCT 4 Pillars

  • 1. Powerful accelerator, the LNL RFQ accelerator

5 MeV 30 mA proton beam ===> 1014 s-1 neutron production rate

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The AB-BNCT 4 Pillars

  • 2. Safe target handling, the LNL design

in collaboration with TECNOMOTIVE s.r.l. (Pd):

Target extraction room RFQ proton beam Beam Shaping Assembly BNCT beam port Target remote handling system

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in collaboration with TECNOMOTIVE s.r.l. (Pd):

The AB-BNCT 4 Pillars

  • 2. Safe target handling, the LNL design
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CH NH2 O (HO)2B CH2 C OH H S

10B

Na +

P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The 4 AB-BNCT Pillars

  • 3. Selective Boron Carrier, Actual Commercial Compounds.
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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The 4 AB-BNCT Pillars

  • 3. Tracing Boron carrier, fluorinated BPA and PET .
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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

B4Pc: the selective uptake can be simply traced by fluorescence

Fluorescence micrographs of cells after 24 h incubation with 7 µM DOPC liposome-incorporated B4Pc 1 bright field image, 2 fluorescence of phthalocyanine, 3 fluorescence of endosomal probe Lucifer Yellow, 4 overlay of images 2 and 3

1 2 3 4

E.Friso et al., Photochem.Photobiol. Sci. 5, 39-50, 2006.

The 4 AB-BNCT Pillars

  • 3. Tracing Boron carrier, Boronophtalocyanine and fluorescence induced by a laser beam
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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The 4 AB-BNCT Pillars

  • 4. Microdosimetric detector, the RBE case

P.Colautti et al., ARI 88, 147-152, 2014 J.Guellette et al. Proceedings ICNCT 12,81-84, 2006

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The 4 AB-BNCT Pillars

  • 4. Microdosimetric detector, the RBE case

RBE of BNCT components

(keV/µm)

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The 4 AB-BNCT Pillars

  • 4. Microdosimetric detector, the LNL twin TEPC
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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The 4 AB-BNCT Pillars

  • 4. Microdosimetric detector, the LNL twin TEPC
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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The 4 AB-BNCT Pillars

  • 4. Microdosimetric detector, the LENA reactor BNCT microdosimetric spectrum
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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

CONCLUSIONS

  • 1. BNCT is a tumour radiation therapy useful when a cellular therapy is recommended. It

needs high neutron-fluence rates, so far provided only by nuclear research reactors.

  • 1. New neutron sources based on particle accelerators could give a boost to BNCT
  • studies. Nine AB-BNCT projects are actually running in the world (Italy, Russia, UK,

Japan, Israel, Argentina).

  • 2. A poor 10B carrier specificity limits the BNCT therapeutic advantage. Knowledge of the

10B carrier metabolic distribution in the patient improves the BNCT therapeutic

advantage.

  • 3. The radiation field complexity and the poor knowledge of the radiation field RBE limit

the BNCT therapeutic advantage. Experimental microdosimetry performed with TEPCs

  • r other microdosimetric detectors could improves the BNCT therapeutic advantage.
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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The LNL AB-BNCT Proposed Centre

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The IFMIF AB–BNCT IFMIF Possible Draft

P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

Schematic breakdown of IFMIF-DONES Systems

BNCT HALL

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

BNCT Microdosimetric Spectra

  • Da simulazioni preliminari, il punto meno critico di ancoraggio del moderatore è

la parete di calcestruzzo intorno al tubo di passaggio del fascio.

  • L’ancoraggio del moderatore alla parete di calcestruzzo in questo punto impone

la rotazione di un cilindro di calcestruzzo di 5.5 m di diametro e 1 m di spessore.

  • Il peso di tale ciambella è circa 80 t.
  • Il peso complessivo degli elementi da muovere è maggiore di 110 tonnellate.
  • Il costo di tale sistema rischia di essere eccessivo > 8 M€

Sviluppo di gantry rotante (2)

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P.Colautti IFMIF/ELAMAT Rzeszów 14-15 April 2016

The third pillar: experimental microdosimetric spectrum