Nuclear Medicine & PET Research. F Production. Radiochemie.nl Cursus 18 F chemie

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1 18 F Production 1

2 Outline Cyclotron technique 18 F targetry : Fluoride and Fluorine production 2

3 Main PET Isotopes 11 C : 20 min, b + ( 970 KeV ), 14 N(p,a) 11 C 13 N : 10 min, b + ( 1190 KeV ), 16 O(p,a) 13 N 15 O : 2 min, b + ( 1720 KeV ), 14 N(d,n) 15 O 18 F : 110 min, b + ( 635 KeV ), 18 O(p,n) 18 F 3

4 Cyclotron production volt between D s 300 circles, 600 accelerations of volt = 18 MeV 4

5 Cyclotron 5

6 6

7 IBA 18/9 18 F : 2,3 ml H 2 18 O in nuobium 11 C : 60 ml N 2 + 0,5% O 2 in aluminium 13 N : 2,3 ml H 2 O in nuobium 15 O : 60 ml N 2 in aluminium 7

8 18 F Fluoride production Nuclear reaction 18 O(p,n) 18 F, obtained as Fluoride in water Proton energy from 10 MeV Side reaction 16 O(p,a) 13 N, obtained as nitrates in water Side products no nuclear side reactions 8

9 18 F Fluoride production Nuclear reaction 9

10 18 F Fluoride targetry target foil fill / empty protons Target H 2 18 O target body cooling Important chracteristics for target body material: Heat capacity coefficient (limiting factor for high beam currents: high pressure in target) Radionuclidic side products Chemical purity of [ 18 F]Fluoride from target 10

11 18 F Fluoride target body material Silver Advantage: Disadvantage: - high heat capacity (max ± 40 µa) - no long lived radio isotopes - Silver particles 11

12 18 F Fluoride target body material Titanium Advantage: Disadvantage: - clean 18 F solution - low heat capacity (max ± 30 µa) - 48 V as side product 12

13 Dose rate (msv/h) Activation of Titanium Accumulation of 48 V Production number 13

14 18 F Fluoride target body material Niobium Advantage: - clean 18 F solution - no long lived radio isotopes - high heat capacity (max ± 40 µa) Disadvantage: -? 14

15 Dose rate (Sv/hr) Nuobium activation F Time (hours) 15

16 Pressure (bar) Pressure in different materials Ag Ti Nb Beam intensity (µa) 16

17 Results different target materials Summary of the results after 120 minutes irradiation Target chamber material Ag Ti Nb Energy (MeV) Beam intensity (µa) Thick target yield sat) Radioactivity EOB (Ci)

18 Results at other centers 18

19 Fluoride target 19

20 Fluoride target 20

21 Fluoride target 21

22 Different materials Ti Ag 22

23 18 F Fluoride targetry beam Target volume ± 2.4 ml Target filling ± 2.4 ml max 40 ma 23

24 18 F Fluoride targetry beam Target volume ± 4.5 ml Target filling ± 3.3 ml ma XXXL : 150 ma? 24

25 18 F and [ 18 F]FDG yields uur 40 ma Start synthesis (End of synthesis 166 GBq [ 18 F]Fluoride 130 GBq [ 18 F]FDG) 3 uur 70 ma Start synthesis (End of synthesis 315 GBq [ 18 F]Fluoride 240 GBq [ 18 F]FDG) 25

26 18 F Fluorine production Nuclear reaction 20 Ne(d,a) 18 F or 18 O(p,n) 18 F deuterons from 7 MeV protons from 10 MeV Side reaction - Side products - 26

27 18 F Fluorine targets Target material : Nickel or Monel 1 st irradiation : 18 F fluorine deposit on target wall Empty target, fill with Neon % F 2 Irradiate Electrophilic fluorination, or via intermediate 27

28 18 F Fluorine target Groningen Installed in 1992 Design: Robert Dahl Nickel / 153 ml 30 psi 1% F 2 / 100 psi Neon Yield in 1992: 5 GBq / 50 µa / 1 hour 28

29 18 F Fluorine specific radioactivity Addition of F 2 is essential, but decreases specific radioactivity Typically : less then 1 GBq/µmol Gives problems for receptor studies, however for F-DOPA no problem 29

30 Production results 30

31 Production results Groningen Radionuclide production: Target SCX nickel plated / 150 ml Havar frontfoil (25 um) SCX nickel plated / 150 ml Havar frontfoil (25 um) Targetgas 0,44 % F2 in Neon / 75 psi 0,44 % F2 in Neon / 75 psi Beamcurrent 15 ua 25 ua Irradiation time minutes 120 minutes Preparation for the production 1x conditioning target and lines 1x 3 µah irradiation to waste 1 x conditioning target and lines 1 x 3 µah irradiation to waste Yield [ 18 F]F MBq/μAh at EOB GBq at BOS MBq/μAh at EOB GBq at BOS Specific activity 4.4 ± 1.0 GBq/mmol 10.7 ± 3.0 GBq/mmol 31

32 [ 18 F]F 2 via (p,n) on [ 18 O]O 2 Load target with 20 bars [ 18 O]O 2 Irradiate with 18MeV protons 18 F radicals deposit on target chamber wall Blow [ 18 O]O 2 away (can be trapped in liq N 2 ) Load target with Neon + 0.3% F 2 Irradiate with 18MeV protons again 18 F radicals exchane with F 2 to form [ 18 F]F 2 in Neon Advantage: nuclear reaction much more efficient Higher yield of 18 F (40-50 GBq) Higher specific activity 32

33 Further reading Radiopharmaceuticals for Positron Emission Tomography Ed G. Stöcklin and W.W. Pike Kluwer Academic publishers, Dordrecht, 1993, isbn Nuclear Science series: Fluorine-18 Labeling of Radiopharmaceuticals M.R. Kilbourn National Academy Press, Washington, 1990 Handbook of Radiopharmaceuticals : Radiochemistry and applications Ed MJ Welch, CS Redvanly Wiley, Sussex, 2003, isbn