Sarar technology for the application of Copper-64 in biology and materials science

Abstract

This review provides an overview of the synthesis and metal complexation chemistry of the nitrogen and sulphur donor bicyclic ligands or cages, and the key criteria that led to the design of sarar for the application for 64Cu(II). Aspects of the high yielding synthesis of sarar and strategies for its conjugation to a range of antibodies for targeting colorectal cancer, neuroblastoma and melanoma are described. Free and conjugated to proteins sarar can complex 64Cu(II) rapidly at room temperature and quantitatively; the latter leading to products of high specific activity and purity. The full occupation of the 64Cu(II) ions 6 coordination sites by the sarar cage prevents the ready exchange of the 64Cu(II) from the cage and is the rational for the extraordinary thermodynamic and kinetic stability of 64Cu(II) labelled sarar and its conjugates. It’s in vivo stability is further highlighted by the low uptake and retention of 64Cu-sarar-conjugated antibodies in the liver. Finally, the prospects for the use of the sarar technology in the materials science arena for probing solid liquid interfaces, in particular, the quantification of functional groups on microspheres and in the engineering of novel materials are discussed. © 2008 Edizioni Minerva Medica