2.  Background  Imaging techniques  Reactor production  Accelerator production  The Moly Crisis  Radioisotopes

3. Historical background  Nuclear medicine dates back to as early as the 1800s with the discovery of naturally occurring radioisotopes and the use of x-rays.

4.  Rapid advancements such as the invention of the cyclotron lead to the birth of modern nuclear medicine as we know it today  Nuclear reactors also played a role in the development of nuclear medicine as a method of creating radioisotopes

5.  Radioisotopes of all decays alpha, beta and gamma are used for both treatment and diagnostics in nuclear medicine  Focus here is on diagnostic isotopes that are either gamma or positron emitters. SPECT or PET Therapy alpha Diagnostic gamma Diagnostic Beta +

6. SPECT  Patients are injected with a gamma emitting isotope attached to a targeting ligand for uptake in specific areas of the body  Different length half- lives are suited to different types of procedure e.g. uptake time  2D and 3D maps of an area can be created using a computer model of the signals received.

7. PET  Similar to SPECT but maps created from signals of secondary gammas from positron/e- annihilation

8. Production methods  Once radioisotopes could be manufactured (reactor or accelerator) two different supply methods became available  Direct production  Generator production

9. Direct Production  The direct production of a radioisotope due to the bombardment of a target isotope by a projectile such as a proton, neutron, alpha or deuteron.  The direct production of a radioisotope as a by product of the neutron bombardment inside the target of a research reactor.

10. Generator production  The production of the radioisotope as the decay product of another radioisotope.  Most commonly 99 Mo – 99m Tc  Parent isotope is collected in a column where the daughter isotope can be eluted using various types of solution dependent on isotope and application.  Isotope is then mixed in a pre-prepared kit to form the drug administered to the patient

11. Rector Production  Radioisotopes can also be produced as a by product of spent reactor fuel  Currently the most common production route  However this supply is under threat due to an aging fleet and no replacements

13. MOLY CRISIS  In 2010 the main reactors went off line for an unexpected extended maintenance.  As a result over 80% of the worlds nuclear imaging procedures had to be postponed or cancelled.  The current fleet is old and close to retirement with no back up currently in place another crisis is looming

14. Tc-99m  Half-life: ~6hrs, decay: 140keV gamma  The most common of the medical radioisotopes primarily due to ease of production  Production: Generator via Mo parent – a by product of nuclear reactors  Used for a range of SPECT procedures including: bone, brain, blood, lung scans, heart and tumours

15. Solutions to the crisis  New reactors?  Accelerators? Current cyclotrons? Linacs? Low energy machines?  Other isotopes?

16.  Some factors to consider when determining the most suitable production method Half-life of the isotope in question: is it long enough for direct production, on site or regional supply? Cleanliness of the reaction: how many contaminants are produced alongside the radioisotope of interest and how easily can they be extracted? Natural or enriched targets? How much target material is there? How easily can a target be manufactured and processed? Energy range of incident particles Cheapest supply of incident particle How can we make an isotope more widely available

17. New Reactors

18. Accelerator Approach

19. Solid Targets (1)  Thin and thick Foil  Elemental or mixed composition typically oxide  Created with electroplating

20. Solid Targets (2)  Thick pellet targets  Elemental or mixed composition typically oxide  Created by compression

21. Liquid Targets  Water or molten metal  Compound targets  Contained by metal casing often aluminium or nickel  Flowing targets aid in cooling

22. Gas Targets  Pressurised gas housed in a metal container

23. Electron Machines  Canadian Light Source part of a commission by the Canadian government to find accelerator methods to replace NRU  Uses Bremsstrahlung from an electron linac (35MeV)  Principle has been successfully demonstrated 100 Mo(γ,n) 99 Mo

24. Proton Machines  TRIUMF facility part of the same commission as CLS  Uses ~20MeV Proton Cyclotron  Successfully demonstrated the most favoured approach to accelerator based 99m Tc production 100 Mo(p,2n) 99m Tc

25. TRIUMF Target  Pellet target  Target recycling

26. Low energy accelerators (1)  ns-FFAG E p <16MeV  Can be used with thin or thick targets

27.  ONIAC - Siemens  Electrostatic DC accelerator  ~10MeV  Can be used with thick or thin, solid or liquid targets  Proton or deuteron beam Low energy accelerators (2)

28. Low Energy 99 Mo/ 99m Tc Production Direct 100 Mo(p,2n) 99m Tc 98 Mo(p,γ) 99m Tc Generator 100 Mo(p,pn) 99 Mo

29. 100 Mo(p,2n) 99m Tc  Route with the most potential as focus of the TRIUMF studies  Cross-section peaks above the energy range of interest for low energy production  More efficient at higher energies as proved by TRIUMF is it worth taking forward?

30. 98 Mo(p,γ) 99m Tc  Highest ratio of 99m Tc to 99 Tc  Clean product  Very low threshold, only viable for E p < 5MeV  However total yield not large enough for medical quantities

31. Other SPECT isotopes  Iodine-123  half-life:13.2hrs  Used for thyroid imaging and treatment  Current Production: 124 Te(p,2n) 123 I Internal solid powder targets Targets in both elemental and oxide form

32.  Strontium-87m  half-life:2.8hrs  Used for bone imaging  Current production: Via generator 87 Y (half- life:79.8hrs)  87 Sr(p,n) 87 Y – 87m Sr Elemental or compound target (SrCl 2 ) E p ~ 20MeV  nat Rb(a,xn) 87 Y E a < 26MeV

33.  Gallium-67  Half-life: 3.3 days  Uses: Long half-life useful for slow uptake tumour imaging  Production: nat Zn(p,X) 67 Ga

34. PET isotopes  Typically short-lived positron emitting isotopes  Both complimentary and competitive with SPECT

35. F-18  Half-life: 110mins  Uses: brain scans, cardiology and tumour monitoring.  FDG the primary F-18 drug  Production: 18 O(p,n) 18 F, 20 Ne(d,a) 18 F, 20 Ne(p,2pn) 18 F  Both liquid and gaseous targets used

36. 18 O(p,n) 18 F  Liquid target of H 2 18 O housed in a metal container or gaseous 18 O  Near threshold proton beam E p <15MeV  F-18 extracted as aqueous fluoride

37. 20 Ne(d,a) 18 F  Gas target of H 2 Ne so that F-18 is created as H 18 F which can be extracted as aqueous fluoride

38. C-11  Half-life: 20mins  Uses: similar to F-18, easily inserted into many biological structures replacing the existing carbon  Production: 14 N(p,a) 11 C  Gas target

39. Cu-64  Half-life:12.7hrs  Uses: joint therapy and diagnostic tool  Production: 64 Ni(p,n) 64 Cu, 68 Zn(p,an) 64 Cu  E p ~ 16MeV

41. Ga-68  Half-life:68mins  Uses: similar to F-18 but preferred for areas with high background FDG uptake such as brain tumours  Production: currently via generator 68 Ge(half-life:270days) nat Zn(a,X) 68 Ge, nat Ga(p,X) 68 Ge

42.  Low energy direct production of 68 Ga  enriched single isotopic solid target  E p ~ 10MeV  68 Zn(p,n) 68 Ga

43. Summary  Radioisotopes are a vital life saving tool  Many methods of manufacture, the most suitable system is determined by the isotope in question i.e. half-life, contaminants, target material abundance  Currently dependent on reactor based methods which lead to supply crisis

45. Summary (2)  Community looking to expand accelerator based methods  Introducing potential new isotopes

46. Questions?