Production of radioisotopes: where it all begins!

1. Production of radioisotopes: where it all begins! Thomas J. Ruth TRIUMF Vancouver, Canada

2. Radiochemical tracers Probe biochemical systems by labeling compounds with known biological behavior.

3. Tracer Principle • Tracer behaves in a similar way to the components of the system to be probed. • Tracer does not alter the system in any measurable fashion. • Tracer concentration can be measured.

4. Specific Activity • Radioactivity per mass – MBq/mmole • To maintain tracer priniciple must have the highest SA possible. • 370 MBq @ 370 GBq /mmole = 1014 molecules

5. Sources of radioisotopes: Naturally occurring – 235U Fission – 99Mo 99mTc Neutron capture – 186Re Charged particle – 123I

6. Radioisotope production is truly Alchemy where you change one element into another!

7. Choice of method The best possibility for achieving high SA is through charged particle reactions.

8. Notation 185Re + n = 186Re + g 185Re(n,g)186Re 18O + p = 18F + n 18O(p,n)18F

9. Excitation function

10. R = Ins (1 – e-lt) Where R – production rate I – beam flux s – cross section (1 – e-lt) – saturation factor

11. Positron Emitters

12. Production Methods

13. Gas Target

14. Liquid Target

15. Parameters • target construction • target constituents • irradiation conditions • energy • current • temperature • pressure • dose • optimize yield and specific activity

16. [11C]CO2 • small volume aluminum targets • O2 may or may not be added • H. J. Ache, A.P. Wolf, Radiochim. Acta Vol 6, p32, 1966 • primary products are CN and CO at low dose (<0.1 eV/molecule) • higher doses radiolytically oxidize these to CO2 • typical dose 150 eV/molecule

17. [11C]CH4 • initial work to produce HCN in target required flow-thru quartz body due to dose dependence and CN reactivity. • large aluminum or small nickel targets reported to work well. • D.R. Christman et al. Int. J. App. Rad. Isot., Vol. 26, p435, 1975. • G.-J. Meyer et al. Radiochimica Acta, Vol. 50, p43, 1990.

18. [11C]CH4 • Reaction Pathway protons N2 + H2 11C + N2 + H2 11CN 11CN + H2 HCN HCN CH4 + NH3 radiolysis

19. [11C]CH4 at TRIUMF • initial results with cylindrical target, 5% H2 very poor (30% theoretical) • conical target, 10% H2 (50% theoretical) • NH3 in equilibrium & only dependent on amount of H2 • residual fields show 11C produced but not extracted in gas phase • Recently have starting using Nb target chamber with excellent yields

20. [18F]HF • first water target was Kilbourn et al. Int. J. Appl. Rad. Isot. Vol. 35, p599, 1984. • target materials, titanium, silver, nickel, gold, plated • A.D. Roberts et al. NIM B99, p797, 1995. • C. E. Gonzalez Lepara & B. Dembowski, Appl. Rad. Isot. Vol. 48, p613, 1997.

21. [18F]F2 • An 18O2 Target for the Production of [18F]F2 R. J. Nickles, M.E. Daube, and T.J. Ruth, Int. J. Appl. Radiat. Isot. Vol. 35, p117, 1984 • experience with 20Ne(d,a)18F + carrier 19F2 • subsequent irradiations > theoretical • target wall acting as a holding pool for F • NiF2 on target walls is not passive • proton-only accelerators & 3x yield

22. Non-reactive gases (CF4, NF3,…) Atomic flourine F Molecular flourine F2 NiF2 target surface Nickles’ 4 Compartment Model k6 k7 k2 k1 k3 k5 k4

23. Two-shot Method • target evacuated • O2 released to target and irradiated • O2 cryotrapped out • target evacuated with mech. pump • target loaded with 20-200umole F2 + inert gas (Ne, Ar, Kr, Xe) • 18F2 released from target via isotopic exchange

24. 18O2 Gas Handling system

25. [18F]F2 • several reports of single and double shot production methods implemented • reported use of aluminum target bodies in 1991 by Bida et al. • Proc. of IVth Int. Workshop on Targetry and Target Chemistry. • Development of an improved target for [18F]F2 production. A.D. Roberts, T.R. Oakes, and R.J. Nickles Applied Rad. Isot. Vol. 46, p87, 1995

26. [18F]F2 • advantages of aluminum: • stability • passivation • activation • machinability • cost

27. [18F]F2 yield vs. 19F2 conc. mmol 19F2 Electrophilic 18F from a Siemens 11MeV Proton-only Cyclotron Chirakal et al. Nucl. Med. Biol. Vol. 22, p111, 1994.

28. [18F]F2 yield vs. Irradiation time A.D. Roberts, T.R. Oakes, R.J. Nickles Development of an improved target for [18F]F2 production. App. Rad. Isot. Vol. 46, p87, 1995.

29. [18F]F2 • Proton Irradiation of [18O]O2: Production of [18F]F2 and [18F]F2 + [18F]OF2 A. Bishop, N. Satyamurthy, G. Bida, G. Hendry, M. Phelps, J.R. Barrio Nucl. Med. Biol. Vol. 23, p189, 1996 • targets of aluminum, copper, gold plated copper, nickel, cone and cylinders • single and two shot • multiple recoveries

30. Multiple Recoveries • A. Bishop et al., Nucl. Med. Biol. Vol. 23, p189, 1996

31. Choice of Production Method • the threshold energy for initiating the reaction • the energy where the maximum cross section is found • the physical properties of the target material • the physical properties of the product

32. Choice of Production Method -continued • the chemical properties of the target • the chemical properties of the product • the ease of separation of the product and target • and the ability of converting the product into a useful labeling form.

33. Confounding issues

34. In Target Chemistry? For a 15 cm target at 10 atm N2 and a 10.5 MeV proton beam.. Heselius, Abo Akademi

35. Ep= 13.0 MeV P0= 300 psi Havar window

36. 90% Thick Ep= 13.0 MeV P0= 300 psi Havar window

37. 75% Thick Ep= 13.0 MeV P0= 300 psi Havar window

38. 50% Thick Ep= 13.0 MeV P0= 300 psi 4.2 MeV Havar window

39. He cooling foil from TR13 Target Note heat mark

40. Courtesy of John Lenz

41. Courtesy of John Lenz

44. Water Cooled Grid Target Roberts & Barnhart, U. Wisc.

48. Accelerator Production of High Specific Activity Therapeutic Radionuclides: Production of High LET Radioisotopes at TRIUMF-ISACThomas J. RuthUBC/TRIUMF PET Program

49. "It's not for content but for appearance"Pierce

50. Candidate radionuclides for radioimmunotherapy: