Brookhaven National Laboratory Nuclear Chemistry Summer School Sarah Weßmann 07/27/2006

1. Radionuclide generators for Nuclear Medicine Brookhaven National Laboratory Nuclear Chemistry Summer School Sarah Weßmann 07/27/2006

2. Overview • Theoretical Background • Definition • Setup • Examples • Role of radionuclide generator • Properties/ requirements • Conclusion

3. Overview • Theoretical Background • Definition • Constitution • Examples • Role of radionuclide generator • Properties/ requirements • Conclusion

4. “A radionuclide generator... ..can be defined as an effective radiochemical separation of decaying ´parent´ and ´daughter´ radionuclides such that the daughter is obtained in a pure radiochemical and radionuclidic form. The parent system is called the ´cow´ from which the daughter radioactivity is ´milked´”. Gobal B. Saha. Fundamentals of Nuclear Pharmacy. 4th ed. Springer, 1998 F. Rösch, F.F. Knapp. Radionuclide generators. Handbook of Nuclear Chemistry, Vol. 4, 2002

5. To ´milk´ the´cow´?

6. Setup

7. Examples

8. Examples

9. Examples - 68Ge /68Ga • Positron emitter • T1/2=1.135 h • first in 1996 • for imaging myocardial perfusion • for neuroendocrine tumors with [68Ga]DOTATOC • Ga3+ in macrocyclic bifunctional chelator DOTA • DOTATOC has high affinity to somatostatin-receptor in tumors Ga3+ DOTA = Tetra-aza-cyclo-dodecane-tetraacetic acid DOTATOC = (DOTA-Phe,Tyr3-Octreotid)

10. Examples - in-vivo generator • Basics: Molecule carriers are labeled with radionuclide parent • accumulation in the desired organ • shorter half-live daughters are produced ´in-vivo´ • Diagnostic and therapeutical application problem: daughter nuclide is released from the labeled tracer and thus its original position

11. Contents • Theoretical Background • Definition • Setup • Examples • Role of radionuclide generator • Properties/ requirements • Conclusion

12. Role of generator in Nuclear Medicine • George de Hevesy´s tracer concept radionuclides and radioactive molecules are used in nano-molecular concentrations for analysing physiological process in vivo, but have no pharmacologic effect

13. Role of generator in Nuclear Medicine Why are radionuclide daughters not directly produced in reactors or cyclotrons?

14. The role of generator in Nuclear Medicine - Properties • ~95% of nuclear medicine procedures are diagnostic, the rest therapeutic they take place in hospitals or medical departments of universities • generators provide parents which have long enough half-lives to make them easy transportable • cost, availibility generators provide a continuing source of radionuclides, several applications out of a single generator • separation repeatable, simple, easy to handle, convenient, rapid to use

15. The role of generator in Nuclear Medicine - Properties • Conservation of a defined chemical form of parent and daughter • Avoid additional chemical manipulations, breakthrough of parent (toxity) • Expenditure of time to generate the daughter smaller than the parent´s half-live

16. Special properties for clinical application Daughter: • -short-lived radionuclides: could be given in larger dosage, minimal radiation but excellent results • Seperation should result in high yield • To minimize the radiation in short period of time….> daughter nuclide should decay to another long-live or even stable isotope • Radionuclide‘s half-live long enough to reach the targeted organ but not being present more than one day • Good tracebility of the daughter nuclide --- half-live, type of radiation and energy • No- carrier added form

17. Conclusion No- carrier added form • „Convenint alternative to the cost-intensive production production in reactors and cyclotron“ Reasonable cost simple repeatable on demand easy transportable availibility „Convenient

18. Thanks