# Presentation: 129027

## The Role of Copper 

**The Role of Copper **
**in Nuclear Medicine**

**Presentation by**** **
**Frederic Zoller**
**NCSS 2006**

## Why is the use of copper in 
		nuclear medicine so interesting ?

**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**

**Notes:**
One synthese for all isotopes possibel
 versatile applications  radioimmunotherapie

## Properties of copper radionuclides 

**  ****availbility of generator systems**
**  ************-emitter with high abundance**
**  ****high energy ************-emitter**

**Advantages **

**Disadvantages**

**  ****expensive reactor-production**
**  ****high energy cyclotron for ****67****Cu**

- P.J. Blower et al. 1996

**62****Cu**

**64****Cu**

**67****Cu**

**Notes:**
—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.

## Properties of copper radionuclides 

**62****Zn/****62****Cu generator **

**T****1/2****(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 **

## 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 properties are exploited for enzymatic activity**
**most important enzymes: Superoxide dismutase (SOD)**
**Albumin is transport protein of copper in the blood**

**Redox Equilibrium**       **2 Cu(I)  ********  Cu  +  Cu(II)**

**Chemistry and Biochemistry**

**Electron configuration****:****	****Cu(I)   d****10    ****     Cu(II)   d****9****  **

**Notes:**
Cu-complexes as mimics of biologically active protein

## Syntheses of copper-radiopharmaceuticals

***Cu***

***Targeting***
*** ******Molecule***

***Linker***

**Bifunctional chelate agent**

**Coordination of Cu(II) **
**in ****square planar manner**** **

**Syntheses of copper-radiopharmaceuticals**

- [Cu(II)-cyclam]2+

- P.J. Blower et al. 1996

**Notes:**
Via 4 N-atoms and 2 O-atoms

## Syntheses of copper-radiopharmaceuticals

- P.J. Blower et al. 1996

**Conjugation of cyclam-derived ligand to antibody**

**Syntheses of copper-radiopharmaceuticals**

**Notes:**
Targeting molecule
Linker
Metall-complexing group

## Copper-labelled blood flow agnets
The most important clinical application of copper 

***The most important clinical application of copper****** ***

**Applications in Nuclear Medicine**

**62****CuPTSM**** **

- http://www.proportionaltech.com/cuptsm.htm

**evaluate blood flow **
**and metabolism in:**
** ****heart**
** ****brain**
** ****tumour**** **

**Notes:**
Imaging with 62CuATSM as well

## Copper-labeled hypoxia imaging agents 

**Applications in Nuclear Medicine**

**62****CuATSM**** **

- C.J. Anderson et al. 1999

**Detection of ischemia of the:**
**  ****brain**
**  ****heart**
**  ****hypoxic tumor**

**64****CuATSM**** **

**Notes:**
DEF: the body (tissue hypoxia) is deprived of adequate oxygen supply 
62Cu diacetyl bis(N4-methyl-thiosemicarbazone 

## Copper-labelled monoclonal antibodies
Highly selective binding to tumorous tissue

***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

**Applications in Nuclear Medicine**

**64****Cu**** ******** emission of an Auger Electron**
**67****Cu**** ******** beta-minus-emitter (100% abundance)**

**Notes:**
Auger electron  internal conversion

## Copper-labelled monoclonal antibodies
Example: 67Cu-CPTA-C595 antibody

***Example: ******67******Cu-CPTA-C595 antibody***

**Targetting of bladder cancer**

- Novak-Hofer et al. 2002

- Novak-Hofer et al. 2002

- intravenous urography

- gamma camera image

**Applications in Nuclear Medicine**

**Notes:**
Monoclonal antobody recognise a peptide epitope in mucin (gycoprotein), which is up-regulated on tumor

## Development of more applications in targeted radiotherapy

**Future Aspects**

**64****Cu-radiopharmaceuticals**

**„****in vivo generator“ for production of  copper-66**
**suitable for targeted radiotherapy (********-****, 2.6 MeV)**** **** **

**66****Ni-radiopharmaceuticals**

**Radionuclide Cocktail**

**Combination of ****64****Cu and ****67****Cu **
**     ****for increasing the therapeutic efficiency**
**Therapy monitoring with SPECT**
** **

**Notes:**
copper-64 will be most important radioisotop in the future 
parent (66Ni, , 0.2 MeV, half-life 55 h) 

## Vielen Dank

- [engl.: Thank You Very Much]

**Notes:**
copper-64 will be most important radioisotop in the future 
parent (66Ni, , 0.2 MeV, half-life 55 h)