the role of copper in nuclear medicine
TRANSCRIPT
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The Role of Copper The Role of Copper in Nuclear Medicinein Nuclear Medicine
Presentation by Frederic Zoller
NCSS 2006
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Introduction
Why is the use of copper in Why is the use of copper in
nuclear medicine so interesting nuclear medicine so interesting ??
• Occurrence of many isotopes with the same chemical behavior, but different nuclear chemical properties
• Decay of the isotopes is useful for diagnostic imaging and therapy
• Exploitation of different properties for certain applications
PET,PET,SPECT,SPECT,
RITRIT
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Properties of copper radionuclides
• availbility of generator systems• -emitter with high abundance• high energy -emitter
Advantages Advantages
DisadvantagesDisadvantages • expensive reactor-production• high energy cyclotron for 67Cu
P.J. Blower et al. 1996
62Cu64Cu
67Cu
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6262Zn/Zn/6262Cu generator Cu generator
T1/2(Zn) = 9.2h
generator life: ~3 days
• easy handling
• relatively inexpensive
• excellent for routine
clinical use
http://www.proportionaltech.com/generator.htm
Properties of copper radionuclides
Advantages Advantages
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• Cu is the third most abundant natural trace element
• redox properties are exploited for enzymatic activity
• most important enzymes: Superoxide dismutase (SOD)
• Albumin is transport protein of copper in the blood
Redox EquilibriumRedox Equilibrium 2 Cu(I) Cu + Cu(II)
Chemistry and Biochemistry
Electron configurationElectron configuration: Cu(I) d10 Cu(II) d9
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CuCu TargetingTargeting MoleculeMolecule
LinkerLinker
Bifunctional chelate agentBifunctional chelate agent
Coordination of Cu(II) Coordination of Cu(II) in in square planar mannersquare planar manner
Syntheses of copper-radiopharmaceuticals
[Cu(II)-cyclam]2+
P.J. Blower et al. 1996
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P.J. Blower et al. 1996
Conjugation of cyclam-derived ligand to antibodyConjugation of cyclam-derived ligand to antibody
Syntheses of copper-radiopharmaceuticals
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Copper-labelled blood flow agnetsCopper-labelled blood flow agnetsThe most important clinical application of copperThe most important clinical application of copper
Applications in Nuclear Medicine
6262CuPTSMCuPTSM
http://www.proportionaltech.com/cuptsm.htm
evaluate blood flow
and metabolism in:
• heartheart• brainbrain• tumourtumour
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Copper-labeled Copper-labeled hypoxia imaging agentshypoxia imaging agents
Applications in Nuclear Medicine
6262CuATSMCuATSM C.J. Anderson et al. 1999
Detection of ischemia of the:• brain• heart• hypoxic tumor
6464CuATSMCuATSM
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Copper-labelled monoclonal antibodiesCopper-labelled monoclonal antibodiesHighly selective binding to tumorous tissueHighly selective binding to tumorous tissue
Tumor cells up-regulate certain peptide epitopes, which are recognised by the monoclonal antibody
RadioimmunotherapyRadioimmunotherapyExploitation of therapeutic potentialExploitation of therapeutic potential
Applications in Nuclear Medicine
6464CuCu emission of an Auger Electron
6767CuCu beta-minus-emitter (100% abundance)
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Copper-labelled monoclonal antibodiesCopper-labelled monoclonal antibodiesExample: Example: 6767Cu-CPTA-C595 antibodyCu-CPTA-C595 antibody
Targetting of bladder cancerTargetting of bladder cancer
Novak-Hofer et al. 2002 Novak-Hofer et al. 2002
intravenous urography gamma camera image
Applications in Nuclear Medicine
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• Development of more applications in targeted radiotherapy
Future Aspects
6464Cu-radiopharmaceuticalsCu-radiopharmaceuticals
• „in vivo generator“ for production of copper-66
• suitable for targeted radiotherapy (-, 2.6 MeV)
6666Ni-radiopharmaceuticalsNi-radiopharmaceuticals
Radionuclide CocktailRadionuclide Cocktail • Combination of 64Cu and 67Cu
for increasing the therapeutic efficiency
• Therapy monitoring with SPECT
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[engl.: Thank You Very Much]