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.