Brookhaven National LaboratoryBrookhaven National LaboratoryNuclear Chemistry Summer SchoolNuclear Chemistry Summer SchoolSarah WeßmannSarah Weßmann

07/27/200607/27/2006

Radionuclide generators for Radionuclide generators for Nuclear MedicineNuclear Medicine

Overview Overview

Theoretical BackgroundTheoretical Background DefinitionDefinition SetupSetup ExamplesExamples

Role of radionuclide generatorRole of radionuclide generator Properties/ requirementsProperties/ requirements ConclusionConclusion

Overview Overview

Theoretical BackgroundTheoretical Background DefinitionDefinition ConstitutionConstitution ExamplesExamples

Role of radionuclide generatorRole of radionuclide generator Properties/ requirementsProperties/ requirements ConclusionConclusion

“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´?

SetupSetup

Type Generator . System

Parent Main nuclide decay T1/2

Daughter Main Applicationnuclide emissionT1/2

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- 1.135 h ß+ PET

Examples Examples

Type Generator . System

Parent Main nuclide decay T1/2

Daughter Main Applicationnuclide emissionT1/2

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- 1.135 h ß+ PET

ExamplesExamples

Examples - Examples - 6868Ge /Ge /6868GaGao Positron emitter

o T1/2=1.135 h

o first in 1996

o for imaging myocardial perfusion

o for neuroendocrine tumors with [68Ga]DOTATOC

N N

N N

HOOC

HOOC COOH

O

NH

R

DOTA = Tetra-aza-cyclo-dodecane-tetraacetic acid

DOTATOC = (DOTA-Phe,Tyr3-Octreotid)

Ga3+ in macrocyclic bifunctional chelator DOTA

DOTATOC has high affinity to somatostatin-receptor in tumors

Ga3+

•Basics: Molecule carriers are labeled with radionuclide parent accumulation in the desired organ shorter half-live daughters are produced ´in-vivo´

Examples - in-vivo generatorExamples - in-vivo generator

•Diagnostic and therapeutical application

problem: daughter nuclide is released from the labeled tracer and thus its original position

Contents Contents

Theoretical BackgroundTheoretical Background DefinitionDefinition SetupSetup ExamplesExamples

Role of radionuclide generatorRole of radionuclide generator Properties/ requirementsProperties/ requirements ConclusionConclusion

Role of generator in Nuclear Role of generator in Nuclear MedicineMedicine

George de Hevesy´s George de Hevesy´s tracer concepttracer concept

radionuclides and radioactive molecules are radionuclides and radioactive molecules are used in nano-molecular concentrations for used in nano-molecular concentrations for analysing physiological process in vivo, but analysing physiological process in vivo, but have no pharmacologic effect have no pharmacologic effect

Role of generator in Nuclear Role of generator in Nuclear MedicineMedicine

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

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

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

Conclusion

„Convenint alternative to the cost-intensive production production in reactors and cyclotron“

Reasonable costReasonable cost

repeatablerepeatable

No- carrier added formNo- carrier added form

easy transportableeasy transportableavailibilityavailibility

simplesimple

„„ConvenientConvenient

on demandon demand

Thanks