Update from Karolinska

Transcription

1 Scanditronix meeting Uppsala May 23-25, 2018 Update from Karolinska Jonathan Siikanen Department of Medical Radiation Physics and Nuclear Medicine Stockholm, Sweden

2 Stockholm 2 Jonathan Siikanen: Cyclotron Produced Gallium

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4 Scanditronix (SCX) MC 17 in Lund Radionuclide Production with PET Cyclotrons Supervisors: Anders Sandell Sven-Erik Strand Tomas Ohlsson 4 Jonathan Siikanen: Cyclotron Produced Gallium

5 Cyclotron Building at old Karolinska

6 PETtrace Self Shielded

7 Dual Beam 6 Targets: The GEMS PETtrace at Karolinska 2 x 11 C (20.4 min) 2 x 18 F - (109.8 min) 1 x 15 O 2 (2.04 min) 1 x 18 F 2 11 CO 2 (gas) Nuclear reactions 15 O 2 (gas) 1.2 Ci / 50 µa/ 6 min 3 Ci / 55 µa/ 30 min >20 Ci/mmol 14 N(p, ) 11 C 14 N(d,n) 15 O 18 O(p,n) 18 F 20 Ne(d, ) 18 F 18 F - (ion in water) 3 Ci / 40 µa/ 60 min >20 Ci/mmol 18 F 2 (gas) 0.4 Ci / 40 µa/ 60 min

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9 9 New Karolinska Hospital in Solna (NKS)

10 Radiopharmacy operations are located on floors 1, 2 and 3 in Bioclinicum Floor 1: Cyclotrons Floor 2: PET isotopes Floor 2: Mixed isotopes Floor 3: Goods reception Floor 3: Gas storage

11 New Karolinska Hospital in Solna, NKS 11

12 Comecer installs hot cells in the western wall of the radiochemistry lab and in the Radiopharmacy lab 12

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14 2xPETtrace 800 series

15 C70 C C70 Position C71 Solid [ 11 C]CH 4 6 [ 11 C]CH 4 [ 11 C]CO 2 5 [ 11 C]CO F 4 18 F 2 15 O 3 Solid 89 Zr [ 11 C]CH F 1 18 F

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17 Different molecules requires different radionuclides 89 Zr 135 La 64 Cu 89 Zr 58 Co 68 Ga 64 Cu 45 Ti 68 Ga 64 Cu 45 Ti 135 La

18 Position 3: GE/Comecer Solid Target System View from side View from below

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20 cross section (mbarn) Zn(p,n) 68 Ga 68 Zn(p,2n) 67 Ga proton energy (MeV) Cross section for the 68 Zn(p,n) 68 Ga and 68 Zn(p,2n) 67 Ga reactions. Data from TENDL Jonathan Siikanen: Cyclotron Produced Gallium

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24 Cyclotron Production of Gallium Jonathan Siikanen Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital Stockholm, Sweden

25 Publications (PubMed) Ga-68 Number of PubMed publications per year utilizing 68 Ga and other emerging PET isotopes. Source: PubMed (Feb 2018) search terms: 68(-)Ga; Ga(-)68; 68(-)Gallium; Gallium(-)68 25 Jonathan Siikanen: Cyclotron Produced Gallium

26 68 Ge/ 68 Ga generator Approx 2 GBq when its new 26 Jonathan Siikanen: Cyclotron Produced Gallium

27 Los Alamos National Lab-IPF facility (USA), Brookhaven National Lab BLIP facility (USA) ithemba-faure (South Africa) liquid Ga in a Nb container is irradiated in degraded high energy beams with currents between 65 and 85 μa Cyclotron Co. Lt. (Russia-Obninsk) Ga-Ni alloy pressed on a Cu block serves as target and is irradiated with a 23 MeV incident proton beam and a current up to 600 μa (0.601)Ga-69 + p --> 2n + Ge-68 (0.399)Ga-71 + p --> 4n + Ge-68 Comparison of various excitation functions for the (a) Ga(p,xn)68Ge, (b) Ge(p,pxn)68Ge (c) Zn(a,xn)68Ge reactions IAEA RADIOISOTOPES AND RADIOPHARMACEUTICALS SERIES No. 2

28 Direct production An alternative route to generator produced Ga-68 (T 1/2 =68 min, β + =87.7 %, E mean =836 KeV) is charged particle activation of zinc Why? Production capacity Beam on whenever necessary Availability of generators is limited (and they are relatively expensive) Also for Ga-66, (T 1/2 =9.49 h, β + =51 %, E mean =1904 kev), no generator is available

29 Charged particle activation of zinc: 68 Zn(p,n) 68 Ga Electroplated Target Foil Target Solution Target Low to moderate use Solid Target High use or distribution

30 Production route foil: 68 Zn(p,n) 68 Ga Beam Power (watt) = µa x MeV Zinc M.P=693 K (420 C) B.P=1180 K (910 C) 116 W m 1 K 1 (Cu=401 & Ag=429) Gallium M.P=303 K (30 C) B.P=2670 K (2400 C) 64 Zn (0.49), 66 Zn (0.28), 67 Zn (0.04), 68 Zn (0.19) Lawrence s 60-inch cyclotron, circa 1939, showing beam of accelerated ions escaping the accelerator and ionizing the surrounding air causing a blue glow. 30 Jonathan Siikanen: Cyclotron Produced Gallium

31 How Much Can We Produce? As the charged particles continuosly lose kinetic energy when passing through a thick layer of target atoms, the thick target yield is described by Z =charge of the incoming particles M =mass number of the target atoms E threshold to E max =the energy window σ(e)=cross section at a certain energy (de/dx)=mass stopping power in the target λ=decay constant t=irradiation time. The production yield is here given as MBq/µA from the factor of 3.76x

32 Production Capacity GBq (Ci) Particle MeV protons I (µa) Irradiation Time (h) Ga-68 (EOB) Zn-68 Ga-66 (EOB) Zn-natural Generator (0.05) --- Solution Target? (0.1) 0.1 mm (70 mg/cm 2 ) (0.4) 0.8 (0.02) 0.25 mm (180 mg/cm 2 ) (1.4) 1.9 (0.05) 0.5 mm (70 mg/cm 2 ) (2.1) 2.5 (0.07) 13 MeV Protons Range 0.5 mm in Zn

33 Proton Activation of Zinc p,n-reactions Zn-64 Zn-66 Zn-68 Zn-67 4% 19% P 49% 28% Ga-64 T 1/2 =0.04 h Ga-68 T 1/2 =1.1 h Ga-66 T 1/2 =10.4 h Ga-67 T 1/2 =2.7 d 64 Zn (49%), 66 Zn (28%), 67 Zn (4%), 68 Zn (19%) 33 Jonathan Siikanen: Cyclotron Produced Gallium

34 Bombardment Irradiation on nat Zn foils for production of 66 Ga GE PETtrace, 13 MeV, 10 µa Production 1 d before diffusion separation 68 Ga decays away J.W Engle et al. Applied Radiation and Isotopes 70 (2012)

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36 Schematic of Thermal Diffusion Produced Radionuclides Heating Rinsed with weak acid Bombarded foil a) b) c)

37 Diffusion Step Heat Zn-foils 400 C Shake 1 min Remove foil Ar Ar 0.1 mm= min 0.25 mm =2 h 5 ml 0.1 N HCl

38 Elution Good to go? 0.5 % of 100 mg Zn = 5x10 18 atoms 1 GBq of 68 Ga = 6x10 12 atoms Unfortunately not We need further purification Cation exchange AG50W-X8 Flow through 0.05 N HCl Flow through 0.05 N HCl UTEVA (EXC) 15 mg

39 Some Madison/Lund Results > 60 % of foil activity (< 2 % without heating) is extracted < 0.5 % of foil mass lost Ga-trapping in AG50 is ~100 % and 90 % is re-trapped in UTEVA. > 90 % of loaded Ga (on the UTEVA) is eluted in first 200 µl 0.1 N HCl Ga-66-reactivity is GBq/µmol NOTA (at EOB). J. Engle et al Ga-66-reactivity for natzn foil (dissolved) <0.4 GBq/ µmol Electroplated: Ga-66-reactivity of GBq/µmol

40 Discussion Easy to produce ten fold more 68 Ga than from, nowadays available, generators Diffusion step decreases bulk Zn Easier to purify: Lower volumes Diffusion step decreases metal contaminants Reactivities are increased compared to when entire foil is dissolved <0.5 % target loss possibility to reuse of foils (enriched)

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