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1 Publication
1,4,7-Triazacyclononane ligands as bifunctional radiocoppper chelating agents
Stephan, H.; Joshi, T.;
design of tailor-made bifunctional chelating agents (BFCAs) for radioactive transition metals in view of nuclear medical applications as well as acquisition of reliable information about the biodistribution of different materials represents an intensive and rapidly developing field of research [1]. In this context, the tridentate macrocycle 1,4,7-triazacyclononane (TACN) is of special interest since it forms stable complexes with transition metal ions particularly with Cu(II) [2]. Further, the introduction of donor groups, such as pyridyl units, on the TACN scaffold, significantly enhances the thermodynamic stability as well as the kinetic inertness of the Cu(II) complexes formed. Furthermore, the ligand structure offers various possibilities to introduce biological vectors and suitable linkers for tuning the lipophilicity, overall charge and aqueous solubility of the final bioconjugates. For example, TACN ligands with two pyridylmethyl side-arms (DMPTACN derivatives) rapidly chelate copper(II) radionuclides under ambient conditions and the resulting complexes show high in vivo stability. One such derivative, 2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetic acid (DMPTACN-COOH), containing two coordinating picoline groups, not only exhibits excellent in vivo stability after 64Cu radiolabeling, but also allows for direct attachment of vector molecules as well as easy introduction of bioconjugatable functionalities (e.g., maleimide, isothiocyanate) via the carboxylate pendant. This makes DMPTACN-COOH and its derivatives promising BFCAs for radiocopper (DMPTACN-based BFCAs), facilitating the preparation of radiolabeled targeting molecules and bio(nano)materials.
Examples of target-specific peptides and bio(nano)materials equipped with DMPTACN ligands for labeling with 64Cu as an ideal positron emitter are discussed. This enables tumor imaging and the biodistribution of the materials to be studied over a period of days via positron emission tomography (PET).

[1] E. Boros, A. B. Packard, Chem. Rev. 119 (2019) 870-901.
[2] T. Joshi, M. Kubeil, A. Nsubuga, G. Singh, G. Gasser, H. Stephan, ChemPlusChem 83 (2018) 554-564.
  • Lecture (Conference)
    19th International Conference on Biological Inorganic Chemistry, 11.-16.08.2019, Interlaken, Schweiz

Publ.-Id: 29584 - Permalink