Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

The application of radiolabeled peptides in biomedicine is increasing rapidly and offers excellent prospects for the development of target-specific tumor imaging agents. In this perspective, the incorporation of the positron-emitting radionuclide ⁶⁴Cu^II into ligand-peptide conjugates would permit the use of positron emitting tomography (PET) for tumor identification. An important requirement is that the resulting radiocopper-ligand complex is both kinetically and thermodynamically stable in vivo. We have developed a ligand scaffold based on bis(2-pyridylmethyl)triazacyclononane (DMPTACN) that forms very stable CuII complexes [1]. This structure allows for the introduction of linker groups, such as carboxylic acids, maleimide or isothiocyanate, thereby facilitating coupling of targeting molecules.
Among many characteristic targets of cancer tissue, the epidermal growth factor receptor (EGFR) is one of the most important mediators involved in the development of highly malignant tumors. This surface receptor is overexpressed in several tumor entities. The altered expression of EGFR during tumor growth, invasion, and metastasis present an interesting molecular target for tumor diagnosis and therapy.
Meanwhile, some specific peptides are identified capable of recognition EGFR-rich cancer tissue. Among these, the hexapeptide D4 (Leu-Ala-Arg-Leu-Leu-Thr) has been described [2]. We want to present the synthesis of a DMPTACN-peptide conjugate, applying thiourea coupling of the hexapeptide D4 by a DMPTACN isothiocyanate derivative. Radiochemical and radiopharmacological properties will be reported. In vitro binding characteristics of the [⁶⁴Cu]Cu^II-labeled DMPTACN-peptide conjugate in EGFR overexpressing cancer cells ( FaDu, A431) using an immunoprecipitation protocol point to specific interactions.

[1] G. Gasser, L. Tjioe, B. Graham, M. J. Belousoff, S. Juran, M. Walther, J.-U. Künstler, R. Bergmann, H. Stephan, L. Spiccia, Bioconjugate Chem. 2008, 9, 719-730.
[2] S. Song, D. Liu, J. Peng, H. Deng, Y. Guo, L. X. Xu, A. D. Miller, Y. Xu, FASEB J. 2009, 23, 1396–1404.