Development of Copper-based Radiopharmaceuticals
Incorporation of copper(II) radioisotopes, such as 64CuII and 67CuII, into target-specific radiopharmaceuticals requires the use of chelate ligands to bind the radionuclide to a bioactive molecule. An important requirement is that the resulting radionuclide-ligand complex is both kinetically and thermodynamically stable in vivo, in order to minimize the release of the radionuclide to healthy tissue and therefore reduce the background for imaging and minimize radiation exposure to healthy tissue during therapy. A large variety of amine-based polydentate chelate agents, especially mono- and bi-cyclic polyamines, have been investigated in an effort to satisfy these requirements. However, bifunctional chelators, which permit the rapid, unsophisticated labeling of biologically active molecules and also achieve appropriate pharmaceutical targeting have not been described so far.
S. Juran, M. Walther, H. Stephan, R. Bergmann, J. Steinbach, W. Kraus, F. Emmerling, P. Comba
Hexadentate Bispidine Derivatives as Versatile Bifunctional Chelate Agents for Copper(II) Radioisotopes
Bioconjugate Chem. 2009, 20, 347-359.
A. Röhrich, R. Bergmann, A. Kretzschmann, S. Noll, J. Pietzsch, J. Steinbach, H.Stephan
Novel Tetrabranched Neurotensin(8-13) Cyclam Derivative: Synthesis, 64Cu-Labeling and Biological Evaluation
J. Inorg. Biochem. 2011, 105, 821-832.
R. Bergmann, A. Ruffani, B. Graham, L. Spiccia, J. Steinbach, J. Pietzsch, H. Stephan
Synthesis and biological evaluation of 64Cu-labeled bombesin analogs featuring a bis(2-pyridylmethyl) 1,4,7-Triazacyclononane chelator
Eur. J. Med. Chem. 2013, 19, 434-446.