Bispidines as a platform for targeted multimodal imaging

Ligands based on 3,7-diazabicyclo[3.3.1]nonane (bispidine) form very stable coordination compounds, in particular with first row transition metal ions. Considering multiple functionalization, bispidines are promising candidates for pharmaceutical targeting and multimodal imaging. Due to the formation of thermodynamically stable and kinetically inert Cu^II complexes, penta- and hexadentate bispidine ligands are well suited for ⁶⁴Cu positron emission tomography imaging and radiotherapy (⁶⁴Cu/⁶⁷Cu). The bispidine scaffold paves the way for introducing further functionalities, such as targeting units and fluorescence labels, which broadens the scope regarding pharmaceutical targeting and dual labelling (PET and optical imaging). Several bispidine ligands have been developed in order to improve the radiopharmaceutical behavior as well as possibilities for further beneficial functionalization. Variable denticity (tetra-, penta- and hexadentate) with different donor groups, such as amino, amido, pyridine and/or methoxypyridine functionalities allows for tuning properties such as complexation and lipophilicity. These ligands and the important properties of their Cu^II complexes, e.g., stabilities, ligand exchange kinetics, serum stability, partition coefficients ([⁶⁴Cu]Cu-bispidine: n-octanol/water) and biodistribution studies will be reported.