1. The Role of Copper in Nuclear Medicine Frederic Zoller NCSS 2006
Presentation by
Frederic Zoller
NCSS 2006

2. Why is the use of copper in nuclear medicine so interesting ?
Introduction
Why is the use of copper in
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, SPECT, RIT
One synthese for all isotopes possibel
versatile applications  radioimmunotherapie

3. Properties of copper radionuclides
P.J. Blower et al. 1996
62Cu
64Cu
67Cu
b—Emitter with 100% abundance
67Cu accelerator with 200 MeV. But there are only two such accelerators in the US, one of which is at Brookhaven National Laboratory.
availbility of generator systems
b+-emitter with high abundance
high energy b--emitter
Advantages
Disadvantages
expensive reactor-production
high energy cyclotron for 67Cu

4. Properties of copper radionuclides
62Zn/62Cu generator
T1/2(Zn) = 9.2h
generator life: ~3 days
Advantages
easy handling
relatively inexpensive
excellent for routine
clinical use

5. Chemistry and Biochemistry
Redox Equilibrium Cu(I)  Cu + Cu(II)
Electron configuration: Cu(I) d Cu(II) d9
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
Cu-complexes as mimics of biologically active protein

6. Syntheses of copper-radiopharmaceuticalsCu
Linker
Targeting
Molecule
Bifunctional chelate agent
Via 4 N-atoms and 2 O-atoms
Coordination of Cu(II)
in square planar manner
P.J. Blower et al. 1996
[Cu(II)-cyclam]2+

7. Syntheses of copper-radiopharmaceuticals
Targeting molecule
Linker
Metall-complexing group
P.J. Blower et al. 1996
Conjugation of cyclam-derived ligand to antibody

8. Applications in Nuclear Medicine
Copper-labelled blood flow agnets
The most important clinical application of copper
62CuPTSM
evaluate blood flow
and metabolism in:
heart
brain
tumour
Imaging with 62CuATSM as well

9. Applications in Nuclear Medicine Copper-labeled hypoxia imaging agents
Detection of ischemia of the:
brain
heart
hypoxic tumor
C.J. Anderson et al. 1999
62CuATSM
DEF: the body (tissue hypoxia) is deprived of adequate oxygen supply
62Cu diacetyl bis(N4-methyl-thiosemicarbazone
64CuATSM

10. Applications in Nuclear Medicine
Copper-labelled monoclonal antibodies
Highly selective binding to tumorous tissue
Tumor cells up-regulate certain peptide epitopes, which are recognised by the monoclonal antibody
Radioimmunotherapy
Exploitation of therapeutic potential
Auger electron  internal conversion
64Cu  emission of an Auger Electron
67Cu  beta-minus-emitter (100% abundance)

11. Targetting of bladder cancer
Applications in Nuclear Medicine
Copper-labelled monoclonal antibodies
Example: 67Cu-CPTA-C595 antibody
Novak-Hofer et al. 2002
Novak-Hofer et al. 2002
Monoclonal antobody recognise a peptide epitope in mucin (gycoprotein), which is up-regulated on tumor
intravenous urography
gamma camera image
Targetting of bladder cancer

12. Future Aspects 64Cu-radiopharmaceuticals 66Ni-radiopharmaceuticals
Development of more applications in targeted radiotherapy
66Ni-radiopharmaceuticals
„in vivo generator“ for production of copper-66
suitable for targeted radiotherapy (b-, 2.6 MeV)
copper-64 will be most important radioisotop in the future
parent (66Ni, b-, 0.2 MeV, half-life 55 h)
Radionuclide Cocktail
Combination of 64Cu and 67Cu
for increasing the therapeutic efficiency
Therapy monitoring with SPECT

13. [engl.: Thank You Very Much]
Vielen Dank
copper-64 will be most important radioisotop in the future
parent (66Ni, b-, 0.2 MeV, half-life 55 h)
[engl.: Thank You Very Much]