Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Rigid bispidine (3,7-diazabicyclo[3.3.1]nonane) derivatives have been shown to form stable complexes, particularly with first row transition metal ions [1]. The variable number, type and position of donor groups provide a variety of tailor-made coordination sites for specific metal ions. Furthermore, the bispidine skeleton opens suitable pathways to introduce biomolecules, which are important in view of the pharmaceutical targeting of such complexes. Due to these interesting features, bispidines are predestined as attractive bifunctional chelating agents for the development of target-specific copper-based radiopharmaceuticals. In this perspective, a hexadentate bispidine ligand consisting of pyridine units in the positions C-2, C-4, N-3, and N-7 was conjugated to the tumour-seeking peptide bombesin. The ⁶⁴Cu-labeled bioconjugate is accumulated in human prostate tumors to allow clear visualization of the tumor tissue [2].
In order to optimize the radiopharmaceutical behavior, further bispidine ligands have been developed with different denticity (tetra-, penta, hexadentate) with pyridine and/or methoxypyridine donor groups and with the possibility to introduce functionalities, such as targeting units and fluorescence labels in view of pharmaceutical targeting as well as dual labeling (PET and optical imaging).
These ligands and the important properties of their Cu^II complexes, e. g. stabilities, exchange kinetics and partition coefficients (⁶⁴Cu: octanol/water) will be reported.

[1] P. Comba, M. Kerscher, W. Schiek, Progr. Inorg. Chem. 2008, 55, 613-704.
[2] S. Juran, M. Walther, H. Stephan, R. Bergmann, J. Steinbach, W. Kraus, F. Emmerling, P. Comba, Bioconjugate Chem. 2009, 20, 347-359.