Exceptionally fast formation of stable rigidified cross-bridged complexes formed with Cu(ii) isotopes for molecular imaging

Abstract

⁶⁴Cu is considered to be one of the most promising radioisotopes in radiotheranostics (combining therapeutics with diagnostics) because its positron emission is suitable for PET imaging while the combination of its β⁻ and Auger electrons delivers a therapeutic effect. In this work, we present a thorough coordination chemical characterization of two Cu(II) complexes formed from the cross-bridged pentaazamacrocyclic CB-15aneN₅ and its bifunctional derivative. The Cu(II) chelates possess high thermodynamic stability, fast complexation and moderate inertness under harsh conditions (t_1/2 = 2.3 h, 5 M HCl, 50 °C). EPR measurements and DFT calculations were carried out for characterizing their structure in solution. Furthermore, the radiolabeling experiments performed with ⁶¹Cu(II) confirmed the fast complexation even in the μM concentration range at pH = 6.0. On the basis of these results, the CB-15aneN₅ ligand family serves as an excellent platform for Cu(II) complexation in radiotheranostics.