Molecular imaging of cancer using bispidine ligands

The development of multi-functional complexing agents for radiometal nuclides with a view of nuclear medical application represents a field of research that is intensively dealt with and has rapidly been developing. In this context, ligands that form highly stable metal complexes and additionally possess several different functional groups are of particular interest. This enables the simultaneous introduction of targeting, solubilizing and, for example, fluorescent units into the relevant metal complexes.

Ligands based on 3,7-diazabicyclo[3.3.1]nonane (bispidine) form very stable coordination compounds, in particular with CuII. Due to the formation of thermodynamically and kinetically stable CuII complexes, bispidine ligands are well suited for in vivo application in cancer imaging (⁶⁴Cu^II) and radiotherapy (⁶⁴Cu^II, ⁶⁷Cu^II). Since they are also relatively easy to functionalize with multiple modalities, they are ideal chelators for the design of novel multimodal imaging agents. The bispidine scaffold has a number of options for derivatization that permit the introduction of additional functions such as biological vectors and fluorescence molecules.

Here, the important properties of ⁶⁴Cu^II-labeled bispidine complexes, e. g. stabilities, ligand exchange kinetics, serum stability, partition coefficients (n-octanol/water) and biodistribution data will be reported. It can be concluded that ⁶⁴Cu^II-labeled bispidine derivatives with fluorescent tags have considerable potential for targeted dual imaging using positron emission tomography (PET) and fluorescence imaging.