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1 Outline 1. Historical introduction and basics of radiation protection 2. Modern medical diagnostics o CT, NMR, SPECT, PET o 18-F production o The SWAN project in Bern 3. Particle accelerators for radioisotope production 4. Physics and medicine: an ordinary case in modern cardiology EPFL SB - 2/4 1
2 Medical imaging is essential in modern medicine and the high precision of hadrontherapy would be useless without it EPFL SB - 2/4 2
3 Diagnostics is essential! Computed Tomography (CT) Measurement of the electron density Abdomen Information on the morphology EPFL SB - 2/4 3
4 CT and Hounsfield numbers G. Hounsfield ed 1979 Nobel Prize for Physiology or Medicine Through the measurement of the attenuation coefficient in many directions and slices (i.e. many radiographies) the Hounsfield numbers are calculated for all the Voxels (=VOlume pixels) EPFL SB - 2/4 4
5 Nuclear Magnetic Resonance Felix Bloch and Edward Purcell discover and study NMR In 1954 Felix Bloch became the first CERN Director General EPFL SB - 2/4 5
6 MRI = 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) in tissues Information on the morphology EPFL SB - 2/4 6
7 A MRI scanner EPFL SB - 2/4 7
8 MRI morphological imaging EPFL SB - 2/4 8
9 SPECT = Single Photon Emission Computed Tomography In reactors slow neutrons produce 98 Mo + n = 99 Mo + γ 99 Mo (66 h) = 99m Tc (6 h) + e - + ν gamma of 0.14 MeV Emilio Segrè 1937: Discovery of element 43 Technetium : discovery of 99m Tc with E. McMillan (m stands for metastable) 97 Tc(2.6 My) EPFL SB - 2/4 9
10 The Mo-99/Tc 99/Tc-99m 99m generator Developed at Brookhaven National Laboratories (BNL) in the late fifties Tc has a known and relatively easy chemistry Many molecules can be produced It opened the way to modern functional imaging i using radioisotopes 1966: first commercial generator A modern Tc-99mgenerator EPFL SB - 2/4 10
11 The molybdenum technetium generator EPFL SB - 2/4 11
12 The element 43 The element 43 was missing In 1925 W. Noddack and I. Tacke announced the discovery of Rhenium (75) and Masurium (43) In 1934 Fermi and his group were bombarding all the elemnts with slow neutrons and Segrè was in charge of procuring the different elements but asking for a sample of Masurium he was answerd Numquam vidi EPFL SB - 2/4 12
13 The discovery of technetium EPFL SB - 2/4 13
14 The discovery of technetium Lawrence was using deflectors for the cyclotron made of Molybdenum (42) Segrè thought : Molybdenum + proton = 43! In February 1937 Segrè received a letter from Lawrence with some Molybdenum coming from the deflectors and the element 43 was identified with the help of a chemist (Carlo Perrier) The element 43 was called Technetium since it is the first element artificially produced (the most stable isotope has an half-life life of 4.2 x 10 6 years) EPFL SB - 2/4 14
15 85% of all nuclear medicine examinations use technetium produced by slow neutrons in reactors liver lungs bones Lead collimators to channel the gammas of 0.14 MeV SPECT scanner Measurement of the density the molecules which contain technetium Information on morphology and/or metabolism Rotating head With detectors 0.14 MeV gammas EPFL SB - 2/4 15
16 SPECT images Healty Alchool addict Drug addict Encephalitis EPFL SB - 2/4 16
17 The problem of the shortage of Tc-99m EPFL SB - 2/4 17
18 Positron Emission Tomography (PET) FDG with 18 F is the most used drug (half life 110 minutes) Measurement of the density of 18 F through back-to-back gamma detection Information on metabolism Protons ~15-20 MeV, ~50 μa Gamma ray detectors (Ex. BGO crystals) PET tomograph Cyclotron PET image CT-PET EPFL SB - 2/4 18
19 How does it work? H 18 2 O water is bombarded with protons to produce 18 F Fluoro-Deoxy-D-Glucose (FDG) is synthesized Glucose FDG FDG is transported to the hospital FDG is injected into the patient FDG is trapped in the cells that try to metabolize it Concentration builds up in proportion to the rate of glucose metabolism Tumors have a high rate of glucose metabolism and appear as hot spots in PET images EPFL SB - 2/4 19
20 FDG synthesis C H O 2-deoxy-2-[ D-glucose 18 F]fluoro-D-glucose : CH ( 18 2 OH (CHOH) 4 CHO FDG) 18 F EPFL SB - 2/4 20
21 PET images (1) 18FDG/PET images The cocaine addict has depressed metabolism! EPFL SB - 2/4 21
22 PET images (2) EPFL SB - 2/4 22
23 PET images (3) EPFL SB - 2/4 23
24 The BGO calorimeter of the L3 experiment at LEP (CERN ) BGO crystals have been developed for detectors in particle physics BGO crystals Precise measurement of the energy deposited by the particles Almost 4 π coverage EPFL SB - 2/4 24
25 The new diagnostics: CT/PET morphology metabolism David Townsend CERN: Uni Ginevra UPSM Pittsburgh and Ronald Nutt (CTS CTI) EPFL SB - 2/4 25
26 PET can help for planning in radiation therapy R. Nutt et al., CLINICAL PHARMACOLOGY & THERAPEUTICS, Vol. 81 Num. 6, Pag. 792, June 2007 EPFL SB - 2/4 26
27 Doses in medical diagnostics EPFL SB - 2/4 27
28 Exercise: the production of FDG for PET EPFL SB - 2/4 28
29 The full FDG-PET chain Courtesy IBA EPFL SB - 2/4 29
30 Basic data 20 MeV proton beam (cyclotron) Current : 50 μa FWHM : about 15 mm Target : 99% 18-O enriched water Reaction : 18-O (p,n) 18-F Courtesy ACSI Fluorine 18 : half-life life t 1/2 =110 min. Irradiation time 60 min. What is the value of the 18-F activity produced? One TR19 cyclotron by the company ACSI (Vancouver, Canada) is installed at the Policlinico Gemelli in Rome It is daily used for FDG production EPFL SB - 2/4 30
31 The target Courtesy Pipes for cooling. Why? Let s suppose that the beam completely stops in the target: 20 MeV x 50 μa A x (1/e) = 1000 W 1 cal = 4.18 J i.e. 1 cm 3 of water passes between 0 and 100 degrees in less than 0.5 seconds! EPFL SB - 2/4 31
32 Scheme & questions Enriched water target 20 MeV proton (about 1 cm (about 1 cm 3 ) Does the proton stop in water? Sometimes the reaction 18-O (p,n) 18-F occurs. Probability? EPFL SB - 2/4 32
33 Range of the protons in water Range (cm) Reihe Proton Energy (MeV) Important to remember : 200 MeV 27 cm EPFL SB - 2/4 33
34 Range of protons in water ) Range (cm Proton Energy (MeV) Reihe1 20 MeV cm All protons stop in the target EPFL SB - 2/4 34
35 Residual range Energy (MeV) Range (cm) MeV proton Path (cm) Energy (MeV) The reaction can take place in any point of the path i.e. at different energies! A useful link : physics.nist.gov NIST National Institute of Standards and technology EPFL SB - 2/4 35
36 The cross section For the exercise we will consider an average value of 100 mb for all the energies (1 barn = cm 2 ) EPFL SB - 2/4 36
37 Calculations How many 18-O targets are there? 20 g (18+1+1) of enriched H2O contain N 0 molecules x / 20 3 x O atoms/cm 3 How many bullets per second? Current / charge of the proton EPFL SB - 2/4 37
38 Calculations N R I N = σ t L Δ t t e V N R number of reactions i.e. number of 18-F nuclides produced σ I e cross section beam current charge of the electron N t number of traget 18-O nuclei V L t Δt volume of the target thickness of the target Irradiation time interval? EPFL SB - 2/4 38
39 Calculations Thickness of the target range = 0.42 cm Result 1 In 60 minutes : N 0 = 2 x F nuclei are produced Which is the corresponding activity? N(t)=N N 0 xexp(-t/ t/τ) At t=0 the activity dn/dt is: N 0 /τ F-18 : t 1/2 = 110 min τ = t 1/2 / ln 2 = 158 min = 9480 s Activity : A = 2 x Bq (Bq Bequerel) 1 Ci = 3.7 x Bq (Ci Curie) Result 2 The produced activity is about 6 Ci at the end of the irradiation EPFL SB - 2/4 39
40 Δ N = A Δt N t) Irradiation N( t) = Aτ (1 e Δt τ but 18-F decays during irradiation 1.2 ( 1 Decay t /τ ) ion Fraction of saturat If t<<τ the effect can be neglected If t>>τ saturation effect : production ~ decay F Time (min) For 18-F : the regime is far from saturation for t<120 min. Exercise Taking this effect into account about 4.5 Ci of activity are produced in 60 min. irradiation EPFL SB - 2/4 40
41 A realistic supply chain EPFL SB - 2/4 41
42 Exercise: Verify the range of 18 MeV protons in water using SRIM EPFL SB - 2/4 42
43 The SWAN Project at the Inselspital in Bern Isotope building under construction! Proton therapy centre under study! EPFL SB - 2/4 43
44 The SWAN Project Scope: constitute t a combined centre for Radioisotope production Proton therapy Research Short history 2006/2007 first feasibility studies by Inselspital + Uni Bern End 2007 approval and constitution of the main structure 2008 detailed studies of the Isotopen part 2009 start for the construction of the Isotope building 2009 study for the implantation of the proton therapy centre Innovative structure involving public and private partners. Stakeholders: Inselspital University of Bern Private investors EPFL SB - 2/4 44
45 The group SWAN stands for SWiss hadron Founded at the end of 2007 Shareholders: Inselspital, University of Bern, private investors Inselspital- Foundation SWANtec Holding AG SWISS HADRON FOUNDTION SWAN Isotopen AG SWAN Hadron AG EPFL SB - 2/4 45
46 Structure of the isotope building EPFL SB - 2/4 46
47 The 18 MeV cyclotron laboratory Beam line Physics Laboratory Cyclotron Workshop EPFL SB - 2/4 47
48 Grundsteinlegung (March 3 rd 2010) EPFL SB - 2/4 48
49 Status of the construction (March 2010) EPFL SB - 2/4 49
50 Status of the construction (May 27th 2010) EPFL SB - 2/4 50
51 Status of the construction (June 28th 2010) EPFL SB - 2/4 51
52 Installation of the bunker doors (June 29th 2010) EPFL SB - 2/4 52
53 The cyclotron bunker (September 1st 2010) EPFL SB - 2/4 53
54 Many possible research activities Fundamental physics Positronium Particle detectors Beam monitoring Gamma-ray Resonant Absorption (GRA) related activities Innovative detectors (tests, calibrations, etc.) Applied physics PIXE (Proton Induced X-ray Emission) PIGE (Proton Induced Gamma Emission) PALS (Positron Annihilation Lifetime Spectroscopy) py) TLA (Thin Layer Activation) Radiation bio-physics EPFL SB - 2/4 54
55 Many possible research activities Targets Radiochemistry Clinical research Oncology Neurology Cardiology Dedicated irradiation chamber in the beam line vault (Picture from CNA, Sevile, Spain) EPFL SB - 2/4 55
56 Radiation protection issues To screen 511 kev photons: lead (about 10 cm) in hot cells Lead: ρ=11.3 g/cm 3 ; 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 EPFL SB - 2/4 56
57 Radiation protection issues What about the cyclotron? The target t is a very powerful neutron source! p (18-O, 18-F) n Neutrons are very dangerous (W in the range 10-20) Neutrons become thermal neutrons and produce activation! The choice of the materials is important! EPFL SB - 2/4 57
58 Shielding against neutrons EPFL SB - 2/4 58
59 Shielding 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 EPFL SB - 2/4 59
60 If you want to know more Bern, June 6 th and 7 th, EPFL SB - 2/4 60
61 All this is possible thanks to artificially produced isotopes EPFL SB - 2/4 61
62 The first table of isotopes Georgio Fea. Il Nuovo Cimento 2 (1935) 368 EPFL SB - 2/4 62
63 End of part II EPFL SB - 2/4 63
III. Proton-therapytherapy. Rome SB - 2/5 1
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