OutlineOutline

1.1. Historical introduction and basics of radiation protectionHistorical introduction and basics of radiation protection1.1. Historical introduction and basics of radiation protectionHistorical introduction and basics of radiation protection

2.2. Modern medical diagnosticsModern medical diagnosticsoo CT, NMR, SPECT, PETCT, NMR, SPECT, PEToo 1818--F productionF productionoo The SWAN project in BernThe SWAN project in Bernoo The SWAN project in BernThe SWAN project in Bern

3.3. Particle accelerators for radioisotope productionParticle accelerators for radioisotope production

4.4. Physics and medicine: an ordinary case in modern cardiologyPhysics and medicine: an ordinary case in modern cardiology

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Medical imaging is essential in modern medicineMedical imaging is essential in modern medicine

…and the high precision of hadrontherapy would be useless without it…and the high precision of hadrontherapy would be useless without it

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Diagnostics is essential!Diagnostics is essential!

Computed Tomography (CT)Computed Tomography (CT)

•• Measurement of the electron densityMeasurement of the electron density

I f ti th h lI f ti th h l

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AbdomenAbdomen •• Information on the morphologyInformation on the morphology

CT and Hounsfield numbersCT and Hounsfield numbers

G. Hounsfield G. Hounsfield G ou s e dG ou s e d

1979 Nobel Prize for Physiology or Medicine 1979 Nobel Prize for Physiology or Medicine

ThroughThrough thethe measurementmeasurement ofof thethe attenuationattenuation coefficientcoefficient inin manymany directionsdirectionsandand slicesslices (i(i..ee.. manymany radiographies)radiographies) thethe HounsfieldHounsfield numbersnumbers areare calculatedcalculated

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(( yy g p )g p )forfor allall thethe VoxelsVoxels (=VOlume(=VOlume piXELS)piXELS)

Nuclear Magnetic ResonanceNuclear Magnetic Resonance

19381938--19451945

Felix Bloch and Edward Purcell Felix Bloch and Edward Purcell

discover and studydiscover and study

NMRNMR

In 1954 Felix Bloch becameIn 1954 Felix Bloch became

th fi t CERN Di t G lth fi t CERN Di t G l

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the first CERN Director Generalthe first CERN Director General

MRI = Magnetic Resonance ImagingMRI = Magnetic Resonance Imaging

1. Main magnet (0.5-1 T)

2. Radio transmitter coil

3. Radio receiver coil

4. Gradient coils

•• Measurement of the density of the protons (water) Measurement of the density of the protons (water) in tissuesin tissues

•• Information on the morphologyInformation on the morphology

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Information on the morphologyInformation on the morphology

A MRI scannerA MRI scanner

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MRI morphological imagingMRI morphological imaging

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SPECT = Single Photon Emission Computed Tomography SPECT = Single Photon Emission Computed Tomography

In reactors slow neutrons produce98Mo + n = 99Mo + γ

99Mo (66 h) = 99mTc (6 h) + e- + ν

gamma of 0.14 MeV

Emilio SegrEmilio SegrèèEmilio SegrEmilio Segrèè1937: Discovery of element 43 “Technetium” 1937: Discovery of element 43 “Technetium” 9797Tc(2.6 My)Tc(2.6 My)

1938: discovery of1938: discovery of 99m99mTcTc

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1938: discovery of 1938: discovery of TcTcwith E. McMillan (m stands for metastable) with E. McMillan (m stands for metastable)

The MoThe Mo--99/Tc99/Tc--99m generator99m generator

Developed at Brookhaven National Laboratories (BNL) in the late fiftiesTc has a known and relatively easyTc has a known and relatively easy chemistry

– Many molecules can be producedIt d th t d f ti l i i– It opened the way to modern functional imaging using radioisotopes

1966: first commercial generator

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A modern Tc-99mgenerator

The molybdenum technetium generatorThe molybdenum technetium generator

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The element 43The element 43

•• The element 43 was The element 43 was missing missing

•• In 1925 W. Noddack and I. In 1925 W. Noddack and I. Tacke announced the Tacke announced the di f Rh i (75)di f Rh i (75)discovery of Rhenium (75) discovery of Rhenium (75) and and Masurium (43)Masurium (43)

•• In 1934 Fermi and his In 1934 Fermi and his group were bombarding group were bombarding “all” the elemnts with slow “all” the elemnts with slow

t d S è it d S è ineutrons and Segrè was in neutrons and Segrè was in charge of procuring the charge of procuring the different elementsdifferent elements

•• …but asking for a sample …but asking for a sample of Masurium he was of Masurium he was answerd “Numquam vidi”answerd “Numquam vidi”

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answerd “Numquam vidi”…answerd “Numquam vidi”…

The discovery of technetiumThe discovery of technetium

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The discovery of technetiumThe discovery of technetium

Lawrence was using deflectors for the cyclotron made of Lawrence was using deflectors for the cyclotron made of Molybdenum (42)Molybdenum (42)Molybdenum (42)Molybdenum (42)

Segrè thought : Molybdenum + proton… 42 + 1 = 43 !Segrè thought : Molybdenum + proton… 42 + 1 = 43 !

In February 1937 Segrè received a letter from Lawrence with some In February 1937 Segrè received a letter from Lawrence with some Molybdenum coming from the deflectors andMolybdenum coming from the deflectors andMolybdenum coming from the deflectors and…Molybdenum coming from the deflectors and…

…the element 43 was identified with the help of a chemist (Carlo …the element 43 was identified with the help of a chemist (Carlo p (p (Perrier)Perrier)

Th l t 43 ll d T h ti i it i th fi t l tTh l t 43 ll d T h ti i it i th fi t l tThe element 43 was called Technetium since it is the first element The element 43 was called Technetium since it is the first element artificially produced (the most stable isotope has an halfartificially produced (the most stable isotope has an half--life of 4.2 x life of 4.2 x 101066 years)years)

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SPECT scannerSPECT scanner85% of all nuclear medicine85% of all nuclear medicine%%

examinations use technetiumexaminations use technetium

produced by slow neutronsproduced by slow neutrons

•• Measurement of the Measurement of the density the molecules density the molecules which contain which contain p yp y

in reactorsin reactorstechnetiumtechnetium

•• Information on Information on morphology and/ormorphology and/or

… liver… liver

lungslungs

morphology and/or morphology and/or metabolismmetabolism

bones …bones …

Lead collimators to channel

Rotating headWith detectors

Lead collimators to channel the gammas of 0.14 MeV

0.14 MeVgammasgammas

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SPECT imagesSPECT images

Healty Alchool addict

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Drug addict Encephalitis

www.brainplace.com

The problem of the shortage of TcThe problem of the shortage of Tc--99m99m

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Positron Emission Tomography (PET)Positron Emission Tomography (PET)

•• FDG with FDG with 1818F is the most used drug F is the most used drug (half life 110 minutes)(half life 110 minutes)

•• Measurement of the density ofMeasurement of the density of 1818FFProtonsProtons

•• Measurement of the density of Measurement of the density of 1818F F through backthrough back--toto--back gamma detectionback gamma detection

•• Information on metabolismInformation on metabolism

~15~15--20 MeV, ~50 20 MeV, ~50 μμAA

PET t h

Gamma ray detectors (Ex. BGO crystals)

CyclotronPET tomograph

PET image CT PETPET image CT-PET

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How does it work?How does it work?

HH221818OO water is bombarded with protons to produce water is bombarded with protons to produce 1818FF

FluoroFluoro--DeoxyDeoxy--DD--Glucose (FDG) is synthesizedGlucose (FDG) is synthesized

Glucose FDG

FDG is transported to the hospitalFDG is transported to the hospitalFDG is transported to the hospitalFDG is transported to the hospital

FDG is injected into the patientFDG is injected into the patient

FDG is trapped in the cells that try to metabolize itFDG is trapped in the cells that try to metabolize it

Concentration builds up in proportion to the rate of glucose metabolismConcentration builds up in proportion to the rate of glucose metabolism

Tumors have a high rate of glucose metabolism and appear as “hot spots” in Tumors have a high rate of glucose metabolism and appear as “hot spots” in

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PET imagesPET images

FDG synthesisFDG synthesis

CCCC

OOOO

HH

22--deoxydeoxy--22--[[1818F]fluoroF]fluoro--DD--glucose (glucose (1818FDG)FDG)D-glucose : CH2OH (CHOH)4 CHO1818FF

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PET images (1)PET images (1)

•• 18FDG/PET images 18FDG/PET images

•• The cocaine addict has depressed metabolism !The cocaine addict has depressed metabolism !

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pp

PET images (2)PET images (2)

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PET images (3)PET images (3)

EPFL - 11.11.10 - SB - 2/4 23www.drugabuse.gov

The BGO calorimeter of the L3 experiment at LEP The BGO calorimeter of the L3 experiment at LEP (CERN 1989(CERN 1989--2000)2000)

BGO crystals have been developed for detectors in particle physicsBGO crystals have been developed for detectors in particle physics

11000 BGO crystals11000 BGO crystalsPrecise measurement of the energy deposited by the particlesPrecise measurement of the energy deposited by the particlesAl t 4Al t 4

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Almost 4 Almost 4 ππ coveragecoverage

The new diagnostics: CT/PETThe new diagnostics: CT/PET

morphology metabolismmorphology metabolism

David TownsendDavid Townsend

CERN: 1970CERN: 1970--7878

Uni GinevraUni Ginevra

UPSM PittsburghUPSM PittsburghUPSM PittsburghUPSM Pittsburgh

andand

Ronald NuttRonald Nutt

(CTS (CTS –– CTI)CTI)

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PET can help for planning in radiation therapyPET can help for planning in radiation therapy

R. Nutt et al., CLINICAL PHARMACOLOGY & R. Nutt et al., CLINICAL PHARMACOLOGY & THERAPEUTICS,THERAPEUTICS,

81 6 92 20081 6 92 200

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Vol. 81 Num. 6, Pag. 792, June 2007Vol. 81 Num. 6, Pag. 792, June 2007

Doses in medical diagnosticsDoses in medical diagnostics

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Exercise: the production of FDG for PETExercise: the production of FDG for PET

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The full FDGThe full FDG--PET chainPET chain

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Courtesy IBACourtesy IBA

Basic dataBasic data

20 MeV proton beam (cyclotron)20 MeV proton beam (cyclotron)Courtesy ACSICourtesy ACSI

Current : 50 Current : 50 μμAA

FWHM : about 15 mmFWHM : about 15 mm

Target : 99% 18Target : 99% 18--O enriched waterO enriched water

Reaction : 18Reaction : 18--O (p,n) 18O (p,n) 18--FF

Fluorine 18 : halfFluorine 18 : half--life tlife t1/21/2=110 min.=110 min.

Irradiation time 60 min.Irradiation time 60 min.One TR19 cyclotron by the company ACSIOne TR19 cyclotron by the company ACSI

(Vancouver, Canada) is installed at the (Vancouver, Canada) is installed at the What is the value of the 18What is the value of the 18--F F activity produced?activity produced?

( , )( , )Policlinico Gemelli in RomePoliclinico Gemelli in Rome

It is daily used for FDG productionIt is daily used for FDG production

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The targetThe target

C tC tCourtesyCourtesy

Pipes for cooling. Why?Pipes for cooling. Why?Let’s suppose that the beam completely stops in the target:Let’s suppose that the beam completely stops in the target:Let s suppose that the beam completely stops in the target:Let s suppose that the beam completely stops in the target:

20 MeV x 50 20 MeV x 50 μμA x (1/e) = 1000 WA x (1/e) = 1000 W1 cal = 4 18 J i e 1 cm1 cal = 4 18 J i e 1 cm33 of water passes between 0 and 100 degreesof water passes between 0 and 100 degrees

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1 cal = 4.18 J i.e. 1 cm1 cal = 4.18 J i.e. 1 cm of water passes between 0 and 100 degreesof water passes between 0 and 100 degrees

in less than 0.5 seconds !in less than 0.5 seconds !

Scheme & questionsScheme & questions

Enriched waterEnriched water

target target 20 M V t20 M V t (about 1 cm(about 1 cm33))20 MeV proton20 MeV proton

•• Does the proton stop in water?Does the proton stop in water?

•• “Sometimes” the reaction 18“Sometimes” the reaction 18--O (p,n) 18O (p,n) 18--F occurs. Probability?F occurs. Probability?Sometimes the reaction 18Sometimes the reaction 18 O (p,n) 18O (p,n) 18 F occurs. Probability?F occurs. Probability?

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Range of the protons in waterRange of the protons in water

30.00

35.00

25.00

)

15.00

20.00

Ran

ge (c

m)

Reihe1

10.00

R

0.00

5.00

0 00 50 00 100 00 150 00 200 00 250 000.00 50.00 100.00 150.00 200.00 250.00

Proton Energy (MeV)

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Important to remember : 200 MeV → 27 cmImportant to remember : 200 MeV → 27 cm

Range of protons in waterRange of protons in water

0.90

1.00

0 60

0.70

0.80)

0.40

0.50

0.60

Ran

ge (c

m

Reihe1

0.20

0.30

0.00

0.10

0.00 10.00 20.00 30.00 40.00

Proton Energy (MeV)

20 MeV → 0 4 cm20 MeV → 0 4 cm –– All protons stop in the targetAll protons stop in the target

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20 MeV → 0.4 cm 20 MeV → 0.4 cm –– All protons stop in the targetAll protons stop in the target

Residual rangeResidual range

Energy (MeV) Range (cm)

20 0.4215 0.2510 0.125 0.036

0 0.42 1.0

0

0.17 0.30

20 15 10

Path (cm)Path (cm)

E (M V)E (M V)20 MeV proton20 MeV proton

The reaction can take place in any point of the path The reaction can take place in any point of the path

020 15 10 Energy (MeV)Energy (MeV)

i.e. at different energies !i.e. at different energies !A useful link : A useful link :

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physics.nist.gov physics.nist.gov –– NIST National Institute of Standards and technologyNIST National Institute of Standards and technology

The cross sectionThe cross section

For the exercise we will consider an average valueFor the exercise we will consider an average value

of 100 mb for all the energiesof 100 mb for all the energies

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(1 barn = 10(1 barn = 10--2424 cmcm22))

CalculationsCalculations

How many 18How many 18--O targets are there?O targets are there?How many 18How many 18--O targets are there?O targets are there?20 g (18+1+1) of enriched H2O contain N20 g (18+1+1) of enriched H2O contain N00 moleculesmolecules

2323 // 2222 O /O / 33→ 6.022 x 10→ 6.022 x 102323 / 20 → 3 x 10/ 20 → 3 x 102222 1818--O atoms/cmO atoms/cm33

How many “bullets” per second?How many “bullets” per second?

Current / charge of the protonCurrent / charge of the protonCurrent / charge of the protonCurrent / charge of the proton

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CalculationsCalculations

tLNIN tt

R Δ××××= σ tLVe

N tR Δσ

NNRR number of reactions i.e. number of 18number of reactions i.e. number of 18--F nuclides producedF nuclides producedσσ cross sectioncross sectionσσ cross sectioncross sectionII beam currentbeam currentee charge of the electroncharge of the electronNNtt number of traget 18number of traget 18--O nucleiO nucleiVV volume of the targetvolume of the targetLLtt thickness of the targetthickness of the targetΔΔtt Irradiation time intervalIrradiation time interval

??

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CalculationsCalculations

Thickness of the target → range = 0.42 cmThickness of the target → range = 0.42 cm

Result 1Result 1In 60 minutes : NIn 60 minutes : N00 = 2 x 10= 2 x 101515 1818--F nuclei are producedF nuclei are produced

Which is the corresponding activity? Which is the corresponding activity? N(t)=NN(t)=N00 x exp (x exp (--t/t/ττ))N(t) NN(t) N00 x exp (x exp ( t/t/ττ))At t=0 the activity dN/dt is: NAt t=0 the activity dN/dt is: N00//ττFF--18 : t18 : t1/21/2 = 110 min → = 110 min → τ =τ = tt1/21/2 / ln 2 = 158 min = 9480 s/ ln 2 = 158 min = 9480 sActivity : A = 2 x 10Activity : A = 2 x 101111 Bq (Bq → Bequerel)Bq (Bq → Bequerel)1 Ci = 3.7 x 101 Ci = 3.7 x 101010 Bq (Ci → Curie)Bq (Ci → Curie)

Result 2Result 2The produced activity is about 6 Ci at the end of the irradiationThe produced activity is about 6 Ci at the end of the irradiationp yp y

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…but 18…but 18--F decays during irradiationF decays during irradiation

τttNtAN Δ

×−Δ×=Δ )(1

1.2

ion 18-F

τ

IrradiationIrradiation 0.6

0.8

of s

atur

at

IrradiationIrradiationDecayDecay

0.2

0.4

Frac

tion

o

)1()( /ττ teAtN −−×= 00 100 200 300 400 500 600 700

Time (min)F

•• If t<<If t<<ττ the effect can be neglectedthe effect can be neglected

•• If t>>If t>>ττ saturation effect : production ~ decaysaturation effect : production ~ decay

•• For 18For 18--F : the regime is far from saturation for t<120 min.F : the regime is far from saturation for t<120 min.

•• ExerciseExercise Taking this effect into account about 4 5 Ci ofTaking this effect into account about 4 5 Ci of

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•• Exercise Exercise –– Taking this effect into account about 4.5 Ci of Taking this effect into account about 4.5 Ci of activity are produced in 60 min. irradiationactivity are produced in 60 min. irradiation

A realistic supply chainA realistic supply chain

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Exercise:Exercise:

Verify the range of 18 MeV protons in water usingVerify the range of 18 MeV protons in water usingVerify the range of 18 MeV protons in water using Verify the range of 18 MeV protons in water using SRIM SRIM

www.srim.orgwww.srim.org

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The SWAN Project at the Inselspital in BernThe SWAN Project at the Inselspital in Bern

I t b ildiIsotope building

under construction! Proton therapy

centre

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under study!

The SWAN ProjectThe SWAN ProjectS tit t bi d t fS tit t bi d t fScope: constitute a combined centre forScope: constitute a combined centre for

Radioisotope productionRadioisotope productionProton therapyProton therapyProton therapyProton therapyResearchResearch

Short historyShort historyShort historyShort history2006/2007 first feasibility studies by Inselspital + Uni Bern2006/2007 first feasibility studies by Inselspital + Uni BernEnd 2007 approval and constitution of the main structureEnd 2007 approval and constitution of the main structure2008 detailed studies of the “Isotopen” part2008 detailed studies of the “Isotopen” part2009 start for the construction of the “Isotope building”2009 start for the construction of the “Isotope building”2009 study for the implantation of the proton therapy centre2009 study for the implantation of the proton therapy centre2009 study for the implantation of the proton therapy centre 2009 study for the implantation of the proton therapy centre

Innovative structure involving public and private partners.Innovative structure involving public and private partners.Stakeholders:Stakeholders:Stakeholders:Stakeholders:

InselspitalInselspitalUniversity of BernUniversity of Bern

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yyPrivate investorsPrivate investors

The groupThe group

SWAN stands for SWiss hAdroNSWAN stands for SWiss hAdroNFounded at the end of 2007Founded at the end of 2007Shareholders: Inselspital, University of Bern, private investorsShareholders: Inselspital, University of Bern, private investors

Inselspital-

F d tiFoundation

SWISS HADRONSWANtec Holding AG

SWISS HADRON

FOUNDTION

SWAN

Isotopen AG

SWAN

Hadron AGIsotopen AG Hadron AG

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Structure of the isotope buildingStructure of the isotope building

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The 18 MeV cyclotron laboratoryThe 18 MeV cyclotron laboratory

Physics Beam line y

Laboratoryline

WorkshopCyclotron

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Grundsteinlegung (March 3Grundsteinlegung (March 3rdrd 2010)2010)

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Status of the construction (March 2010) Status of the construction (March 2010)

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Status of the construction (May 27th 2010) Status of the construction (May 27th 2010)

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Status of the construction (June 28th 2010) Status of the construction (June 28th 2010)

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Installation of the bunker doors (June 29th 2010) Installation of the bunker doors (June 29th 2010)

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The cyclotron bunker (September 1st 2010) The cyclotron bunker (September 1st 2010)

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Many possible research activitiesMany possible research activitiesFundamental physicsFundamental physics

PositroniumPositronium

Particle detectorsParticle detectorsBeam monitoringBeam monitoringggGammaGamma--ray Resonant Absorption (GRA) related activitiesray Resonant Absorption (GRA) related activitiesInnovative detectors (tests, calibrations, etc.)Innovative detectors (tests, calibrations, etc.)

Applied physicsApplied physicsPIXE (Proton Induced XPIXE (Proton Induced X ray Emission)ray Emission)PIXE (Proton Induced XPIXE (Proton Induced X--ray Emission)ray Emission)PIGE (Proton Induced Gamma Emission)PIGE (Proton Induced Gamma Emission)PALS (Positron Annihilation Lifetime Spectroscopy)PALS (Positron Annihilation Lifetime Spectroscopy)( p py)( p py)TLA (Thin Layer Activation)TLA (Thin Layer Activation)

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Radiation bioRadiation bio--physicsphysics

Many possible research activitiesMany possible research activities

TargetsTargetsTargetsTargets

RadiochemistryRadiochemistryyy

Clinical researchClinical researchOncologyOncologyNeurologyNeurologyCardiologyCardiologyCardiologyCardiology

Dedicated irradiation chamber in the Dedicated irradiation chamber in the beam line vault beam line vault

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(Picture from CNA, Sevile, Spain) (Picture from CNA, Sevile, Spain)

Radiation protection issuesRadiation protection issues

• To screen 511 keV photons:

• lead (about 10 cm) in hot cellslead (about 10 cm) in hot cells

• Lead: ρ=11.3 g/cm3 ; μρ=1.81 cm-1; 10 cm Reduction factor = 1.4x10-8

• tungsten (about 5 cm) for transport containers

Hot cells host radiochemical modules Transport container for the vials

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Radiation protection issuesRadiation protection issues

• What about the cyclotron?

Th t t i f l t !• The target is a very powerful neutron source!

• p (18-O, 18-F) n

• Neutrons are very dangerous (W in the range 10-20) y g ( g )

• Neutrons become “thermal neutrons” and produce activation!

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• The choice of the materials is important!

Shielding against neutronsShielding against neutrons

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Shielding against neutronsShielding against neutrons

• Concrete : λ = 9.6 cm; 200 cm Reduction factor = 9.2x10-10

Polyethylene : λ = 4 17 cm; 87 cm Reduction factor = 9 2x10-10• Polyethylene : λ = 4.17 cm; 87 cm Reduction factor = 9.2x10-10

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If you want to know more…If you want to know more…

Bern, June 6th and 7th, 2011.http://www.lhep.unibe.ch/cyclotron/

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All this is possible thanks to artificially produced All this is possible thanks to artificially produced isotopesisotopesisotopesisotopes

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The first table of isotopes The first table of isotopes

EPFL - 11.11.10 - SB - 2/4 62Georgio Fea. Il Nuovo Cimento 2 (1935) 368

End of part IIEnd of part II

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