Optimization of the bispidine structure for copper radiopharmaceuticals

Rigid bispidine (3,7-diazabicyclo[3.3.1]nonane) derivatives form very stable complexes, particularly with first row transition metal ions. Furthermore, the bispidine skeleton opens suitable pathways to introduce biomolecules, which are important concerning the pharmaceutical targeting of such complexes. Therefore, bispidines are attractive bifunctional chelating agents for the development of target-specific copper-based radiopharmaceuticals.
In order to optimize the radiopharmaceutical behavior, further bispidine ligands have been developed with different denticity (tetra-, penta- and 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 and dual labeling (PET and optical imaging).
These ligands and the important properties of their CuII complexes, e. g. stabilities, ligand exchange kinetics, partition coefficients (64Cu: n-octanol/water) and biodistribution studies will be reported.