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LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the Use of Geant4 for the interpretation of interpretation of irradiation at low dose on irradiation at low dose on melanoma human cells melanoma human cells G.Montarou G.Montarou (LPC Clermont) (LPC Clermont) IN2P3 / CNRS Université Blaise Pascal 24 rue des Landais 63177 AUBIERE Cedex FRANCE

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Page 1: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

LABORATOIRE de PHYSIQUE CORPUSCULAIRE

Use of Geant4 for the Use of Geant4 for the interpretation of irradiation at interpretation of irradiation at low dose on melanoma human low dose on melanoma human

cellscells

G.MontarouG.Montarou(LPC Clermont)(LPC Clermont)

IN2P3 / CNRS Université Blaise Pascal24 rue des Landais 63177 AUBIERE Cedex FRANCE

Page 2: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Who are we ?Who are we ?

LPC (Laboratoire de Physique Corpusculaire) LPC (Laboratoire de Physique Corpusculaire) is one of the laboratories is one of the laboratories ofof the the

« Institut National de Physique Nucléaire et « Institut National de Physique Nucléaire et des Particules » des Particules »

(IN2P3)(IN2P3)

LPC depends also of the Blaise Pascal LPC depends also of the Blaise Pascal University University

► 56 physicists (University or CNRS position)56 physicists (University or CNRS position)► 45 Engineers or technicians45 Engineers or technicians► 24 PhD24 PhD

Page 3: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Who are we ?Who are we ?

You can see more at http://clrwww.in2p3.fr/You can see more at http://clrwww.in2p3.fr/

Page 4: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Where are we ?Where are we ?Clermont-Ferrand is the capital of region Auvergne

Auvergne University, Blaise Pascal University 30 000 students

Page 5: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

What we doWhat we doHigh Energy Experiments at :High Energy Experiments at :

CERN (ATLAS, LHCb, ALICE, NA60), CERN (ATLAS, LHCb, ALICE, NA60), Fermilab (D0), Fermilab (D0), Brookhaven (Phenix),Brookhaven (Phenix),

Nuclear Physics Experiments at :Nuclear Physics Experiments at : GSI (FOPI),GSI (FOPI), TJNAF,TJNAF,

But also Applied Physics with two groups :But also Applied Physics with two groups :

The The PCSV groupPCSV group (1 physicist, 3 PhD and 2 associated engineers) (1 physicist, 3 PhD and 2 associated engineers)

works on the “Data grid” development especially in biomedicalworks on the “Data grid” development especially in biomedical

application (GATE Development on the GRID)application (GATE Development on the GRID)

The The AVIRM groupAVIRM group (4 physicists, 3 PhD and 3 associated (4 physicists, 3 PhD and 3 associated engineers)engineers)

works the interaction of with matter in different fields especially ofworks the interaction of with matter in different fields especially of

the interaction of neutrons with biological matter at low dose the interaction of neutrons with biological matter at low dose

Page 6: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Irradiation with 14 MeV neutron of Human Irradiation with 14 MeV neutron of Human melanomia cells at low dose and low ratemelanomia cells at low dose and low rate

High Radioresistivity to X-ray (3Gy/h)

Hypersensibility of cells to 14 MeV neutron at low dose rate

(5cGy/h)

Cellular reliability curves of human malanoma cells after low dose rate

X-ray and 14 MeV neutrons irradiation

Page 7: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

The observation of this phenomenon push us to study the types of interactions which will take place between the neutrons and the human melanomia cells as well as the amount of energy deposited in the cells.

Same phenomenon observed with C12

Extension of irradiations to human glioblastoma and fibroblast cells

To understand experimental data we need to simulate the interaction of the neutrons with biological matter, down to DNA scale

First step dedicated MC code (DIANE)

ML Nenot PhD Thesis 2003

Page 8: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Neutron-hydrogen collision constitutes the principal interaction of the neutrons with the

biological matterElastic

diffused Neutron

Hydrogène nucleus

Cell

Sub-cellular element

Energy deposited

Incident Neutron

Recoil Proton

electron

RTrack of the recoil

protons

Deposit of energy in the cells is primarily due to the recoil protons

Page 9: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Interaction of 14 MeV Neutrons with waterInteraction of 14 MeV Neutrons with water

Rate of charged particles produced expressed in percentRate of charged particles produced expressed in percent

64,1

26,2

0,58,4

0,54 0 0,260

10203040506070

Page 10: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Energy deposition by the way of secondaries electrons from the interaction of the charged

recoil particles

Energy of these electron go down to very low energy range (10 eV – 100 10 eV – 100 eV)

Need of specific framework to deal with such electron production and propagation in matter

See work of G Paretzke, H. Nikjoo, W Frieldland

Interactions of neutrons with biological matter (like Interactions of neutrons with biological matter (like water): water):

► elastic collisionelastic collision► Inelastic collisionInelastic collision

( n , γ ) Reaction

( n , α ) Reaction

Page 11: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

The ionisation in Standard Geant4The ionisation in Standard Geant4

1- Continue Energy loss by charged Ions:1- Continue Energy loss by charged Ions:

Bethe-BlochBethe-Bloch

where where mm is the mass of the e- is the mass of the e-

rre e is is e-e- radiusradius

nnee is is e- density in the medium e- density in the medium

TTupup is min (Tcut, Tmax is min (Tcut, Tmax))

The maximum of the energie transfered to the e- is :The maximum of the energie transfered to the e- is :

Page 12: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

2- Process of production of deltas e 2- Process of production of deltas e (Discret)(Discret)

The differential cross-section for the ejection The differential cross-section for the ejection of a e-Kinetic energy Tof a e-Kinetic energy T::

The totale cross-section per atome :The totale cross-section per atome :

Page 13: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

At very low proton energy specific parametrisations are used :At very low proton energy specific parametrisations are used :

Se = dE / dX Se = dE / dX is electronic stopping power in eV/1015 atoms/cm2 is electronic stopping power in eV/1015 atoms/cm2

Ai are experimental parameters given by:Ai are experimental parameters given by:

Page 14: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

electron rates ejected by specific recoil electron rates ejected by specific recoil particlesparticles

Electrons éjectés par différents types de particules

78%

0,01%

22,00%

0,40%0%

20%

40%

60%

80%

100%

PROTONS GAMMA Autres Ions(ionisation)

AutresParticules

Page 15: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Energie distribution of the ejected electronsEnergie distribution of the ejected electrons

Page 16: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

The Cucinotta model and its implantation in The Cucinotta model and its implantation in Geant4Geant4

and

(for water)

Page 17: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Comparison Geant4.6.0 Vs Comparison Geant4.6.0 Vs CucinottaCucinotta

Page 18: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Comparison Geant4.6.0 Vs Comparison Geant4.6.0 Vs CucinottaCucinotta

Page 19: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

Experimental Setup

Irradiation bunker

Irradiaton bunker door14 MeV neutron Generator

Zoom

Bottles containing the human melanomia cells

He 3 detector to monitor the neutron flux

Page 20: LABORATOIRE de PHYSIQUE CORPUSCULAIRE Use of Geant4 for the interpretation of irradiation at low dose on melanoma human cells G.Montarou (LPC Clermont)

What we need !What we need !Implantation in GEANT4 of the framework to take into Implantation in GEANT4 of the framework to take into

account:account:► Production of low energy electrons from charges recoil Production of low energy electrons from charges recoil

particles (10 eV – 100 eV),particles (10 eV – 100 eV),► Propagation of these electrons down to a very low Propagation of these electrons down to a very low

energy range,energy range,► Standard Modelisation of cells,Standard Modelisation of cells,A lot of work done by different groups all around A lot of work done by different groups all around the word that appears as dedicated code (PITS, the word that appears as dedicated code (PITS, SRIM, PARTRAC…)SRIM, PARTRAC…)

Could we implement all this existing Could we implement all this existing matter in dedicated matter in dedicated Version of Version of GEANT4 ??GEANT4 ??