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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]