Multi-functional bispidine derivatives as versatile imaging agents

Multi-functional bispidine derivatives as versatile imaging agents

Stephan, H.; Coma, P.

The development of multi-functional complexing agents for radiometal nuclides with a view of nuclear medical application represents a fast developing field of intensive research [1]. A requirement for ligands in this field is fast complexation kinetics and high complex stabilities with specific radiometal ions and ligands which are easy to functionalize with several different groups for linking to biological vectors, nanoparticles and/or fluorescence molecules.

Ligands based on 3,7-diazabicyclo[3.3.1]nonane (bispidine) form very stable transition metal complexes [2]. Due to the formation of thermodynamically and kinetically stable CuII complexes, pentadentate and hexadentate bispidines are very well suited for in vivo application, i.e. for tumor imaging (64CuII) using positron emission tomography (PET) and tumor therapy (64CuII, 67CuII) [3, 4]. The bispidine scaffold has various sites for functionalization that permit the introduction of biomolecules for pharmaceutical targeting and fluorescent units for optical imaging (see Figure 1).

Several bispidine ligands have been developed in order to improve the radiopharmaceutical behavior as well as possibilities for further beneficial functionalization. These ligands and the important properties of their CuII complexes, e.g., stabilities, ligand exchange kinetics, serum stability, partition coefficients ([64Cu]Cu-bispidine: n-octanol/water) and biodistribution studies 64Cu-labeled bispidines will be reported.

1. C. S. Cutler, M. H. Hemmkens, N. Sisay, S. Markai-Huclier. S. S. Jurisson, Chem. Rev. 113, 858 (2013).
2. P. Comba, M. Kerscher, W. Schiek, Prog. Inorg. Chem. 55, 613 (2007).
3. S. Juran, M. Walther, H. Stephan, R. Bergmann, J. Steinbach, W. Kraus, F. Emmerling, P. Comba, Bioconjugate Chem. 20, 347, (2009).
4. P. Comba, S. Hunoldt, M. Morgen, J. Pietzsch, H. Stephan, H. Wadepohl, Inorg. Chem. 52, 8131 (2013).

  • Lecture (Conference)
    5th EuCheMS Chemistry Congress, 31.08.-04.09.2014, Istanbul, Turkey

Publ.-Id: 20695