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

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.

[1]  L. Grøndahl,et al.  Stability and kinetics of acid- and anion-assisted dissociation reactions of hexaamine macrobicyclic mercury(II) complexes , 1997 .

[2]  J. Lewis,et al.  Copper radionuclides and radiopharmaceuticals in nuclear medicine. , 1996, Nuclear medicine and biology.

[3]  A. Beatty,et al.  Synthesis and Characterization of Cobalt-Cage Complexes with Pendant Phenol Groups. , 1996, Inorganic chemistry.

[4]  A. Sargeson.  The potential for the cage complexes in biology , 1996 .

[5]  G. Denardo,et al.  Copper-67-labeled monoclonal antibody Lym-1, a potential radiopharmaceutical for cancer therapy: labeling and biodistribution in RAJI tumored mice. , 1988, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  M. R. Snow,et al.  Analysis of trigonal-prismatic and octahedral preferences in hexaamine cage complexes , 1985 .

[7]  A. Sargeson.  Encapsulated metal ions , 1984 .

[8]  P. A. Lay,et al.  Synthesis and properties of macrobicyclic amine complexes of rhodium(III) and iridium(III) , 1983 .

[9]  P. Boreham,et al.  Novel Cationic Surfactants Derived From Metal Ion Cage Complexes: Potential Antiparasitic Agents , 1995 .

[10]  P. A. Lay,et al.  The Synthesis and Structure of Encapsulating Ligands: Properties of Bicyclic Hexamines , 1994 .

[11]  P. A. Anderson,et al.  Synthesis, Resolution and Kinetics of Electron Self-Exchange of High-Spin Manganese(II)/(III) Cage Complexes , 1993 .

[12]  G. Denardo,et al.  Comparative serum stability of radiochelates for antibody radiopharmaceuticals. , 1987, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.