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Synthesis of 64Cu bifunctional chelators for Positron Emission Tomography (PET) imaging

Dernière mise à jour : mercredi 9 janvier 2013, par Aline NONAT

Positron emission tomography (PET) is a non invasive medical imaging technique used for the diagnostic of some cancers, and for following the evolution of tumors and efficiency of treatments. Images are obtained by injection of a positron-emitting radiotracer (radioactive molecule). Among the principal radiometals employed for PET, 64Cu has known a great interest in recent years. 64Cu has to be incorporated in a bifunctional chelator (BFC). Indeed, this bifunctional property allows on one hand, the formation of a inert metal chelate and on the other hand, the covalent attachment to a bioactive macromolecule or vector, able for example to target high expression of receptors in the case of some diseases as cancers.
Recent works [1] [2] in the lab led us to the synthesis of a new acyclic phosphonated ligand L1 having a great affinity for copper (II). Moreover, copper (II) coordination with L1 is selective compared to others neighboring transition metals. It’s also interesting to note that compared to its analogue containing carboxylic moieties, the presence of phosphonate units confers to L1 a higher stability during the formation of complexes with some metals like copper.

The 99mTc complex with ligand L1 has been injected in mice as a SPECT radiotracor and localises in the cartilage rich regions.

The activated bifunctionnal ligand, L2, has then been synthesized for the labeling of biomolecules. [3], [4]
The labeling was performed on B28-13, a mouse monoclonal antibody specifically recognizing tenascin-C protein in human cancer. Immunofluorescence staining experiments on human colon cancer biopsies confirmed the affinity of the labeled peptide for tenascin-C.

Currents interests are directed towards the labeling of other biomolecules and the synthesis of new bifunctionnal ligands for the complexation of Cu(II).

[1S. Abada, A. Lecointre, M. Elhabiri, L. J. Charbonniere,Dalton Trans., 2010, 39(38), 9055-90627

[2S. Abada, A. Lecointre, I. Déchamps-Olivier, C. Platas-Iglesias, C. Christine, M. Elhabiri, L. Charbonniere, Radiochim. Acta, 2011, 95, 663-678

[3Brevet FR 11- 59210 (12/10/2011)

[4Christine, C. ; Koubemba, M. ; Shakir, S. ; Clavier, S. ; Sabatier, L. ; Saupe, F. ; Orend, G. ; Charbonnière L.J.,Org. Biomol. Chem.,2012, 10, 9183-9190