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

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

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

“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

To ´milk´ the´cow´?

Setup

Examples Type Generator . System Parent Main nuclide decay T1/2 Daughter Main Application nuclide emission Positron emitter 68Ge /68Ga  270.8 d EC 1.135 h ß+ PET Photon emitter 99Mo/ 99mTc 2.74 d ß- 6.006 h y SPECT Particle emitter 90Sr /90Y 28.5 a ß- 2.671 d ß- ERT In vivo 66Ni /66Cu 2.28 d ß-

Examples Type Generator . System Parent Main nuclide decay T1/2 Daughter Main Application nuclide emission Positron emitter 68Ge /68Ga  270.8 d EC 1.135 h ß+ PET Photon emitter 99Mo/ 99mTc 2.74 d ß- 6.006 h y SPECT Particle emitter 90Sr /90Y 28.5 a ß- 2.671 d ß- ERT In vivo 66Ni /66Cu 2.28 d ß-

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)

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

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

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

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

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 Def. Nuclear medicine May have facilities to preparate radiopharmaceuticals Place of producing does not equal place of diagnostic test

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 ) No intermediate

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 -- lead to negligible concentrations---and therefore not invasive

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

Thanks