Synthesis of a new cage ligand, SarAr, and its complexation with selected transition metal ions for potential use in radioimaging

Abstract

A new hexaazamacrobicyclic cage ligand, 1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (SarAr) has been designed for conjugation to proteins. SarAr was synthesised and characterised by microanalyses, 1H NMR and electrospray mass spectrometry. The complexation of selected transition metal ions (Cu(II), Ni(II) and Co(II) at 10−6 M) by SarAr was complete within 30 min over pH 6 to 8. The [64Cu(SarAr)]2+ complex was investigated with a view to applications in radioimaging. The [64Cu(sar)]2+ complex was found to be stable in human plasma for at least 174 h and biodistribution studies in mice, showed that the [64Cu(SarAr)]2+complex was rapidly excreted through the renal system unlike the free 64Cu2+. Overall, the simple synthesis, ready complexation behaviour of SarAr, the kinetic inertness of the [Cu(SarAr)]2+ complex to dissociation of 64Cu and its facile elimination from mice make it an attractive prospect for use in nuclear medicine. © The Royal Society of Chemistry 2001